WorldWideScience

Sample records for human granulocyte-macrophage colony

  1. Culture of human oocytes with granulocyte-macrophage colony-stimulating factor has no effect on embryonic chromosomal constitution

    DEFF Research Database (Denmark)

    Agerholm, Inge; Loft, Anne; Hald, Finn

    2010-01-01

    The effect on ploidy rate in donated human oocytes after in-vitro culture with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; 2 ng/ml) from fertilization until day 3 was examined in a multicentre, prospective placebo-controlled and double-blinded study including 73...

  2. Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma

    DEFF Research Database (Denmark)

    Kharazmi, A; Nielsen, H; Hovgaard, D

    1991-01-01

    Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM-CSF on the neutrophil and monocyte function in patients with lymphoma...

  3. Recombinant human granulocyte-macrophage colony-stimulating factor as treatment for chronic leg ulcers.

    Science.gov (United States)

    Borbolla-Escoboza, J R; María-Aceves, R; López-Hernández, M A; Collados-Larumbe, M T

    1997-01-01

    To evaluate the safety and effectiveness of a single subcutaneous perilesional administration of 300 micrograms of recombinant human granulocyte-macrophage colony stimulating factor (rHGM-CSF) for the treatment of chronic leg ulcers. Prospective, descriptive evaluation in an outpatient group. The Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City. 10 patients with chronic leg ulcers. Ulcer diameter and side effects. After 4 weeks observation, 8 of the 10 ulcers had healed; the other two had a mean diameter decrease of 21%. The only side effect was found in a 58 year old female who complained of moderate perilesional pain two days after having received treatment: it was successfully treated with paracetamol. We believe that a single perilesional subcutaneous administration of rhGM-CSF is safe and effective for the treatment of chronic leg ulcers.

  4. Safety of recombinant human granulocyte-macrophage colony-stimulating factor in healing pediatric severe burns.

    Science.gov (United States)

    Chi, Y F; Chai, J K; Luo, H M; Zhang, Q X; Feng, R

    2015-03-31

    We explored the safety of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for healing burns in children. Subjects were randomly assigned to two groups: the experimental group received external rhGM-CSF gel, and the control group received rhGM-CSF gel matrix components, applied to the burn surface. Neither group was given any other drugs that promote wound healing. Each day we recorded the pulse, body temperature, and respiration status in the two groups. We detected the blood routine, urine routine, and hepatic and renal function before the patients received drug treatment and after 72 h. The wound scab and healing states in the two groups were recorded every 4 days to evaluate wound healing rate and time taken for complete healing. Adverse reactions and their rate of occurrence were also recorded. The median time of healing was 15 days in the experimental group and 19 days in the control group (log-rank χ(2) = 5.139, P 0.05). Compared with saline treatment of severe burns, rhGM-CSF can effectively shorten the healing time without significant adverse reactions, and is an effective and safe treatment for burns in children.

  5. Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    S Montagnani

    2009-12-01

    Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

  6. Cloning and Characterization of the Human Interleukin-3 (IL-3)/IL-5/ Granulocyte-Macrophage Colony-Stimulating Factor Receptor bc Gene: Regulation by Ets Family Members

    NARCIS (Netherlands)

    Dijk, Thamar B. van; Baltus, Belinda; Caldenhoven, Eric; Handa, Hiroshi; Raaijmakers, J.A.M.; Lammers, J.W.J.; Koenderman, L.; Groot, Rolf P. de

    1998-01-01

    High-affinity receptors for interleukin-3 (IL-3), IL-5, and granu-locyte- macrophage colony-stimulating factor (GM-CSF) are composed of two distinct subunits, a ligand-specific a chain and a common ß chain (ßc). Whereas the mouse has two homologous ß subunits (ßc and bIL-3), in humans, only

  7. High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture

    DEFF Research Database (Denmark)

    Shin, Yun-Ji; Hong, Shin-Young; Kwon, Tae-Ho

    2003-01-01

    this problem, we sought an expression system in which heterologous gene expression could be induced at high levels. We selected a rice amylase expression system in which the promoter Ramy3D is induced to express recombinant protein by sucrose starvation. This induction system was found to give good yield......Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) has been previously produced in tobacco cell suspension cultures. However, the amount of hGM-CSF accumulated in the culture medium dropped quickly from its maximum of 150 microg/L at 5 d after incubation. To overcome...... of recombinant hGM-CSF in transgenic rice cell suspension culture and protease activity of this culture medium was low compared to that of tobacco culture system....

  8. The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity

    DEFF Research Database (Denmark)

    Fonnes, Siv; Holzknecht, Barbara Juliane; Gasbjerg, Lærke Smidt

    2017-01-01

    BACKGROUND: Treatment of secondary peritonitis includes surgery and antimicrobial agents. Antimicrobial agents are often administered intravenously, however, the alternative route intraperitoneal administration could be considered. Investigations must be conducted prior to clinical application....... Therefore, we aimed to investigate the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor with regard to its chemical properties and the solution's stability. In addition, the antibacterial effect of the mixed drug solution was compared...

  9. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Induction of retinoic acid receptor-alpha by granulocyte macrophage colony-stimulating factor in human myeloid leukemia cell lines.

    Science.gov (United States)

    Shimizu, T; Takeda, K

    2000-08-15

    We reported previously that treatment with all-trans retinoic acid (ATRA) and granulocyte macrophage colony-stimulating factor (GM-CSF) induces differentiation of human myeloblastic leukemia ML-1 cells to granulocytes, whereas treatment with ATRA alone induces practically no differentiation of these cells. To investigate the mechanism of the synergistic effect of these factors, we examined the effect of GM-CSF on retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in ML-1 cells. We reveal that GM-CSF induces the expression of RAR alpha mRNA and protein and stimulates the binding of nuclear proteins to direct repeat 5, a consensus sequence with high affinity for RAR-RXR heterodimers. Furthermore, expression of CD38 mRNA mediated through RAR alpha is induced synergistically by treatment with ATRA + GM-CSF. These results suggest that GM-CSF stimulates transcriptional activity mediated via RAR alpha in ML-1 cells. The induction of RAR alpha by GM-CSF may therefore be a mechanism for stimulation by GM-CSF. The induction of RAR alpha by GM-CSF was also detected in other myeloid leukemia cell lines (THP-1 and KG-1) that showed a synergistic effect similar to that seen in ML-1 cells in response to ATRA + GM-CSF. We also found that GM-CSF induced the expression of RAR alpha in blood cells obtained from patients with acute myeloid leukemia. This activity of GM-CSF may serve as a useful adjunct to differentiation therapy for retinoic acid-nonresponsive leukemias.

  11. Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas.

    Science.gov (United States)

    Revoltella, Roberto P; Menicagli, Michele; Campani, Daniela

    2012-03-01

    We studied the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptors (GM-CSF.R) in 20 human brain gliomas with different tumor gradings and demonstrated constitutive high levels of both mRNA gene expression and protein production exclusively in the highest-grade tumors (WHO, III-IV grade). Five astrocytic cell lines were isolated in vitro from glioma cells, which had selectively adhered to plates pre-coated with rhGM-CSF. These cells were tumorigenic when xenografted to athymic mice, and produced GM-CSF constitutively in culture. Two lines, particularly lines AS1 and PG1, each from a patient with glioblastoma multiforme, constitutively over-expressed both GM-CSF and GM-CSF.R genes and secreted into their culture media biologically active GM-CSF. Different clones of the AS1 line, isolated after subsequent passages in vitro and then transplanted to athymic mice, demonstrated higher tumorigenic capacity with increasing passages in vivo. Cell proliferation was stimulated by rhGM-CSF in late-stage malignant clones, whereas apoptosis occurred at high frequency in the presence of blocking anti-GM-CSF antibodies. In contrast, rhGM-CSF did not induce any apparent effect in early-stage clones expressing neither GM-CSF nor GM-CSF.R. The addition of rhGM-CSF or rhIL-1β, to cultures induced the overproduction of both GM-CSF and its receptors and increased gene activation for several functional proteins (e.g. NGF, VEGF, VEGF.R1, G-CSF, MHC-II), indicating that these cells may undergo dynamic changes in response to environmental stimuli. These findings thus revealed: (1) that the co-expression of both autocrine GM-CSF and GM-CSF.R correlates with the advanced tumor stage; (2) that an important contribution of GM-CSF in malignant glioma cells is the prevention of apoptosis. These results imply that GM-CSF has an effective role in the evolution and pathogenesis of gliomas. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    expressed on CD34(+) hematopoietic progenitors from human cord blood stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34(+) progenitors. Freshly isolated CD34(+) progenitors expressed low levels of CXCR3 messenger RNA, but this expression was highly up......-regulated by GM-CSF, as indicated by a real-time quantitative reverse transcriptase-polymerase chain reaction technique. gamma IP-10 and Mig induced chemotaxis of GM-CSF-stimulated CD34(+) progenitors by means of CXCR3, since an anti-CXCR3 monoclonal antibody (mAb) was found to block gamma IP-10-induced and Mig......-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m...

  13. Neutralizing antibodies to granulocyte-macrophage colony-stimulating factor, interleukin-1alpha and interferon-alpha but not other cytokines in human immunoglobulin preparations.

    Science.gov (United States)

    Wadhwa, M; Meager, A; Dilger, P; Bird, C; Dolman, C; Das, R G; Thorpe, R

    2000-01-01

    Human immunoglobulin preparations are used therapeutically for various disorders. Such therapy is generally safe but adverse effects occasionally occur in recipients. It has been suggested that antibodies to cytokines present in clinical immunoglobulin products may contribute to undesirable effects in recipients. Therefore, we investigated intravenous and intramuscular immunoglobulin products for the presence of cytokine-specific neutralizing antibodies. Using validated bioassays, we detected neutralizing activity against human granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha2a (IFN-alpha2a) and interleukin-1alpha (IL-1alpha) in immunoglobulin products. We found no neutralization of granulocyte colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12, tumour necrosis factor-alpha, oncostatin M (OSM) and IFN-gamma. Most batches which neutralized IFN-alpha2a activity also neutralized other IFN-alpha subtypes, IFN-omega and IFN-beta. Most products (94%) neutralized the biological activity of GM-CSF. No correlation between batches and their ability to neutralize bioactivities of GM-CSF, IFN-alpha2a and IL-1alpha was found. This neutralizing activity could be traced to plasma pools used for manufacture of immunoglobulins. The neutralization was mediated by specific cytokine antibodies contained within immunoglobulin products as it was present in specific immunoglobulin G (IgG) fractions eluted from cytokine affinity chromatography columns. Specific binding of such IgG fractions to cytokines in immunoblots and in enzyme-linked immunosorbent assays (ELISAs) was observed. This contrasts with the broad non-specific recognition of cytokine proteins observed using unfractionated immunoglobulins in ELISAs. This is the first comprehensive study showing the presence of neutralizing antibodies against GM-CSF, IL-1alpha, or IFN-alpha2a in immunoglobulin products.

  14. Production of recombinant human granulocyte macrophage-colony stimulating factor in rice cell suspension culture with a human-like N-glycan structure.

    Science.gov (United States)

    Shin, Yun-Ji; Chong, Yun-Jo; Yang, Moon-Sik; Kwon, Tae-Ho

    2011-12-01

    The rice α-amylase 3D promoter system, which is activated under sucrose-starved conditions, has emerged as a useful system for producing recombinant proteins. However, using rice as the production system for therapeutic proteins requires modifications of the N-glycosylation pattern because of the potential immunogenicity of plant-specific sugar residues. In this study, glyco-engineered rice were generated as a production host for therapeutic glycoproteins, using RNA interference (RNAi) technology to down-regulate the endogenous α-1,3-fucosyltransferase (α-1,3-FucT) and β-1,2-xylosyltransferase (β-1,2-XylT) genes. N-linked glycans from the RNAi lines were identified, and their structures were compared with those isolated from a wild-type cell suspension. The inverted-repeat chimeric RNA silencing construct of α-1,3-fucosyltransferase and β-1,2-xylosyltransferase (Δ3FT/XT)-9 glyco-engineered line with significantly reduced core α-1,3-fucosylated and/or β-1,2-xylosylated glycan structures was established. Moreover, levels of plant-specific α-1,3-fucose and/or β-1,2-xylose residues incorporated into recombinant human granulocyte/macrophage colony-stimulating factor (hGM-CSF) produced from the N44 + Δ3FT/XT-4 glyco-engineered line co-expressing ihpRNA of Δ3FT/XT and hGM-CSF were significantly decreased compared with those in the previously reported N44-08 transgenic line expressing hGM-CSF. None of the glyco-engineered lines differed from the wild type with respect to cell division, proliferation or ability to secrete proteins into the culture medium. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  15. A neuroprotective function for the hematopoietic protein granulocyte-macrophage colony stimulating factor (GM-CSF)

    National Research Council Canada - National Science Library

    Schäbitz, Wolf-Rüdiger; Krüger, Carola; Pitzer, Claudia; Weber, Daniela; Laage, Rico; Gassler, Nikolaus; Aronowski, Jaroslaw; Mier, Walter; Kirsch, Friederike; Dittgen, Tanjew; Bach, Alfred; Sommer, Clemens; Schneider, Armin

    2008-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago...

  16. [Effects of recombinant human granulocyte-macrophage colony-stimulating factor on wound healing and microRNA expression in diabetic rats].

    Science.gov (United States)

    Liu, Yifeng; Liu, Dewu; Guo, Guanghua; Mao, Yuangui; Wang, Xianlin

    2014-06-01

    To investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats. Eighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test. (1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both

  17. Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

    Directory of Open Access Journals (Sweden)

    Vinicius Canato Santana

    2015-01-01

    Full Text Available T-cell based vaccines against human immunodeficiency virus (HIV generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+ T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.

  18. Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses.

    Science.gov (United States)

    Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

    2015-12-01

    T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.

  19. Cytokine refacing effect reduces granulocyte macrophage colony-stimulating factor susceptibility to antibody neutralization.

    Science.gov (United States)

    Heinzelman, Pete; Carlson, Sharon J; Cox, George N

    2015-10-01

    Crohn's Disease (CD) afflicts over half a million Americans with an annual economic impact exceeding $10 billion. Granulocyte macrophage colony-stimulating factor (GM-CSF) can increase patient immune responses against intestinal microbes that promote CD and has been effective for some patients in clinical trials. We have made important progress toward developing GM-CSF variants that could be more effective CD therapeutics by virtue of being less prone to neutralization by the endogenous GM-CSF autoantibodies that are highly expressed in CD patients. Yeast display engineering revealed mutations that increase GM-CSF variant binding affinity by up to ∼3-fold toward both GM-CSF receptor alpha and beta subunits in surface plasmon resonance experiments. Increased binding affinity did not reduce GM-CSF half-maximum effective concentration (EC50) values in conventional in vitro human leukocyte proliferation assays. Affinity-enhancing mutations did, however, promote a 'refacing effect' that imparted all five evaluated GM-CSF variants with increased in vitro bioactivity in the presence of GM-CSF-neutralizing polyclonal antisera. The most improved variant, H15L/R23L, was 6-fold more active than wild-type GM-CSF. Incorporation of additional known affinity-increasing mutations could augment the refacing effect and concomitant bioactivity improvements described here. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Up-regulation of cluster of differentiation (CD) 11b expression on the surface of canine granulocytes with human granulocyte-macrophage colony-stimulating factor (GM-CSF).

    Science.gov (United States)

    Nakagaki, Kazuhide; Nunomura, Yuka; Uchida, Kanji; Nakata, Koh; Tazawa, Ryushi

    2014-08-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine, sharing a common beta subunit (CDw131) with interleukins 3 and 5. GM-CSF is important for its direct and indirect involvement in host defense. In veterinary medicine, human (h) GM-CSF has been used as a substitute for canine GM-CSF to stimulate canine granulocytes and macrophages. In this study, we compared the effects of three distinct hGM-CSFs produced by bacteria, yeasts and Chinese hamster ovary (CHO) cells with those of Escherichia (E) coli-produced canine GM-CSF on the cluster of differentiation 11b (CD11b) expression in canine granulocytes. The median effective dose (ED50) of hGM-CSFs from bacteria, yeasts and CHO cells was 3.09, 4.09 and 4.27 ng/ml, respectively, with no significant difference among three. In contrast, a significant difference was observed between ED50 of canine GM-CSF (0.56 ng/ml) and three hGM-CSFs according to the paired t-test (Pgranulocytes, but the average activity of the three rhGM-CSFs was approximately 15% of that of canine GM-CSF.

  1. Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Hughes T

    2014-01-01

    Full Text Available Tasha Hughes,1 Robert S Coffin,2 Caroline E Lilley,2 Rafael Ponce,2 Howard L Kaufman1 1Departments of General Surgery and Immunology and Microbiology, Rush University Medical Center, Chicago IL, 2BioVex, Inc, a subsidiary of Amgen, Inc, Sherman Oaks, CA, USA Abstract: Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF, known as talimogene laherparepvec (T-VEC, has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study. Keywords: granulocyte-macrophage colony stimulating factor, herpesvirus, melanoma, oncolytic virus, treatment

  2. Bone marrow changes associated with recombinant granulocyte-macrophage and granulocyte colony-stimulating factors. Discrimination of granulocytic regeneration.

    Science.gov (United States)

    Harris, A C; Todd, W M; Hackney, M H; Ben-Ezra, J

    1994-06-01

    The hematopoietic growth factors recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human granulocyte colony-stimulating factor are associated with changes of the bone marrow. To evaluate the morphologic features and to differentiate them from leukemia, bone marrow specimens from 12 patients who had been treated with one of these agents were evaluated. The bone marrow displayed marked promyelocytic hyperplasia and a less striking increased percentage of myeloblasts. In each of the 11 patients without leukemia at the time of bone marrow biopsy, the percentage of promyelocytes in the bone marrow was greater than that of myeloblasts. Cytologic features of stimulated regeneration included diffuse cytoplasmic hypergranulation of immature neutrophilic precursors that had prominent perinuclear spherical clear areas representing the Golgi zones. With consideration of bone marrow composition and careful attention to cytologic detail, the distinction of bone marrow regeneration from acute leukemia can be made in most patients who are being treated with recombinant hematopoietic growth factors.

  3. A randomized clinical trial to evaluate the effect of granulocyte- macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization

    DEFF Research Database (Denmark)

    Ziebe, Søren; Loft, Anne; Povlsen, Betina B.

    2013-01-01

    To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).......To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR)....

  4. Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

    NARCIS (Netherlands)

    Seymour, JF; Begley, CG; Dirksen, U; Presneill, JJ; Nicola, NA; Moore, PE; Schoch, OD; van Asperen, P; Roth, B; Burdach, S; Dunn, AR

    1998-01-01

    The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF)

  5. Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma.

    Science.gov (United States)

    Hughes, Tasha; Coffin, Robert S; Lilley, Caroline E; Ponce, Rafael; Kaufman, Howard L

    2014-01-01

    Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF), known as talimogene laherparepvec (T-VEC), has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study.

  6. Overexpression of granulocyte macrophage colony stimulating factor in breast cancer cells leads towards drug sensitization.

    Science.gov (United States)

    Chaubey, Nidhi; Ghosh, Siddhartha Sankar

    2015-02-01

    This report describes the effect of overexpressing granulocyte macrophage colony stimulating factor (GMCSF) in breast cancer cells, which otherwise is involved in proliferation and differentiation of granulocyte and macrophage lineages. The purified recombinant GMCSF cytokine is known to exert dose-dependent proliferative response on various cancer cells, but its effect during overexpression is yet to be evaluated. In our present study, we have generated MCF-7 (breast cancer) cells overexpressing GMCSF. Interestingly, cell viability studies showed pronounced sensitivity of GMCSF overexpressing MCF-7 cells towards anticancer drugs, such as, doxorubicin, 5FU and cisplatin. These findings were substantiated by cell cycle analysis of the drug-treated GMCSF overexpressing MCF-7 cells. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results revealed differential expressions of cyclins, and the carboxyfluorescein succinimidyl ester (CFSE)-based assay established decrease in doubling time of GMCSF overexpressed cells with respect to the control populations. Thus, overexpressing of proliferative GMCSF cytokine in breast cancer cells may increase susceptibility to anticancer drugs.

  7. Local delivery of Granulocyte/Macrophage Colony Stimulating Factor protects mice from lethal pneumococcal pneumonia1

    Science.gov (United States)

    Steinwede, Kathrin; Tempelhof, Ole; Bolte, Kristine; Maus, Regina; Bohling, Jennifer; Ueberberg, Bianca; Länger, Florian; Christman, John W.; Paton, James C.; Ask, Kjetil; Maharaj, Shyam; Kolb, Martin; Gauldie, Jack; Welte, Tobias; Maus, Ulrich A.

    2013-01-01

    The growth factor granulocyte/macrophage-colony stimulating factor (GM-CSF) has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.1 protein expression in alveolar macrophages during a 28 day observation period. Pulmonary Ad-GM-CSF delivery two or four weeks prior to infection of mice with S. pneumoniae significantly reduced mortality rates relative to control vector treated mice. This increased survival was accompanied by increased iNOS expression, antibacterial activity and a significant reduction in caspase 3 dependent apoptosis and secondary necrosis of lung sentinel cells. Importantly, therapeutic treatment of mice with recombinant GM-CSF improved lung protective immunity and accelerated bacterial clearance after pneumococcal challenge. We conclude that prophylactic delivery of GM-CSF triggers long-lasting immunostimulatory effects in the lung in vivo and rescues mice from lethal pneumococcal pneumonia by improving antibacterial immunity. These data support use of novel antibiotic-independent immunostimulatory therapies to protect patients against bacterial pneumonias. PMID:22003204

  8. Granulocyte-Macrophage Colony-Stimulating Factor Production and Tissue Eosinophilia in Chronic Rhinitis

    Directory of Open Access Journals (Sweden)

    Peric, Aleksandar

    2016-02-01

    Full Text Available Introduction Granulocyte-macrophage colony-stimulating factor (GM-CSF is a strong proinflammatory cytokine that takes part in allergic nasal inflammation as an eosinophil colony-stimulating factor. However, the role of GM-CSF in non-allergic rhinitis has not been fully explored. Objectives The aim of this investigation was to assess the concentration of GM-CSF in nasal secretions of patients with non-allergic rhinitis with eosinophilia syndrome (NARES in comparison to patients with perennial allergic rhinitis (PAR and healthy subjects, as well as to assess the relationship with the degree of eosinophilic inflammation and clinical characteristics of the patients. Methods Fourteen patients with diagnosis of NARES, 14 PAR patients, and 14 healthy subjects were included in this cross-sectional study. All patients underwent symptom score assessment, nasal endoscopy, allergy testing, and cytological evaluation. The concentration of GM-CSF in nasal secretions of all participants was measured by enzyme-linked immunosorbent assay (ELISA. Results We found significantly higher levels of GM-CSF in patients with NARES than in the control group (p = 0.035. The percent of eosinophils in nasal mucosa was higher in NARES patients in comparison to patients with PAR (p < 0.001 and control patients (p < 0.0001. We found positive correlations between GM-CSF levels and eosinophil counts only in NARES patients. Conclusion The concentrations of GM-CSF in nasal secretions correlate well with eosinophil counts in the nasal mucosa of NARES patients. These facts indicate a possible role of GM-CSF as a favorable marker for assessment of nasal disease severity and the degree of chronic eosinophilic inflammation in the nasal mucosa.

  9. Granulocyte macrophage - colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture.

    Science.gov (United States)

    Truong, M-D; Choi, B H; Kim, Y J; Kim, M S; Min, B-H

    2017-08-01

    To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF + MFX. GM-CSF was administrated intravenously (IV) at 10 μg/kg body weight 20 min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by near-Infrared (NIR) fluorescence imaging and enzyme-linked immune sorbent assay. In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF + MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10 min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects. Copyright © 2017. Published by Elsevier Ltd.

  10. Current status of granulocyte-macrophage colony-stimulating factor in the immunotherapy of melanoma.

    Science.gov (United States)

    Kaufman, Howard L; Ruby, Carl E; Hughes, Tasha; Slingluff, Craig L

    2014-01-01

    In 2012, it was estimated that 9180 people in the United States would die from melanoma and that more than 76,000 new cases would be diagnosed. Surgical resection is effective for early-stage melanoma, but outcomes are poor for patients with advanced disease. Expression of tumor-associated antigens by melanoma cells makes the disease a promising candidate for immunotherapy. The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) has a variety of effects on the immune system including activation of T cells and maturation of dendritic cells, as well as an ability to promote humoral and cell-mediated responses. Given its immunobiology, there has been interest in strategies incorporating GM-CSF in the treatment of melanoma. Preclinical studies with GM-CSF have suggested that it has antitumor activity against melanoma and can enhance the activity of anti-melanoma vaccines. Numerous clinical studies have evaluated recombinant GM-CSF as a monotherapy, as adjuvant with or without cancer vaccines, or in combination with chemotherapy. Although there have been suggestions of clinical benefit in some studies, results have been inconsistent. More recently, novel approaches incorporating GM-CSF in the treatment of melanoma have been evaluated. These have included oncolytic immunotherapy with the GM-CSF-expressing engineered herpes simplex virus talimogene laherparepvec and administration of GM-CSF in combination with ipilimumab, both of which have improved patient outcomes in phase 3 studies. This review describes the diverse body of preclinical and clinical evidence regarding use of GM-CSF in the treatment of melanoma.

  11. Granulocyte Macrophage Colony Stimulating Factor Supplementation in Culture Media for Subfertile Women Undergoing Assisted Reproduction Technologies: A Systematic Review

    Science.gov (United States)

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Salamalekis, George; Creatsa, Maria; Vrachnis, Nikos; Glujovsky, Demián; Iliodromiti, Zoe; Chrelias, Charalampos

    2013-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure. PMID:23509457

  12. Activities of granulocyte-macrophage colony-stimulating factor revealed by gene transfer and gene knockout studies.

    Science.gov (United States)

    Dranoff, G; Mulligan, R C

    1994-01-01

    We used retroviral mediated gene transfer and gene knockout technologies to explore the in vivo functions of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) [1, 2]. In tumor vaccination experiments, GM-CSF was the most potent molecule of a large number of cytokines, adhesion molecules and other immunomodulators for the induction of specific and long-lasting anti-tumor immunity. Vaccination required activities of both CD4 and CD8 positive lymphocytes, and likely involved the augmentation by GM-CSF of host professional antigen-presenting cell function. Mice engineered by homologous recombination techniques in embryonic stem cells to lack GM-CSF demonstrated no significant perturbations in steady-state hematopoiesis. All mutant animals, however, developed the accumulation of surfactant proteins and lipids in the alveolar space, the defining feature of the idiopathic human disorder pulmonary alveolar proteinosis. Surfactant lipid and protein content were increased in the absence of alterations in surfactant protein mRNA, supporting the concept that surfactant clearance or catabolism was perturbed. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be isolated. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis. It is tempting to speculate that the ability of GM-CSF to modulate the uptake and processing of particulate material underlies the mechanisms of immunostimulation and surfactant accumulation.

  13. Persistent Arthralgia Induced by Chikungunya Virus Infection is Associated with Interleukin-6 and Granulocyte Macrophage Colony-Stimulating Factor

    Science.gov (United States)

    Chow, Angela; Her, Zhisheng; Ong, Edward K. S.; Chen, Jin-miao; Dimatatac, Frederico; Kwek, Dyan J. C.; Barkham, Timothy; Yang, Henry; Rénia, Laurent; Leo, Yee-Sin

    2011-01-01

    Background. Chikungunya virus (CHIKV) infection induces arthralgia. The involvement of inflammatory cytokines and chemokines has been suggested, but very little is known about their secretion profile in CHIKV-infected patients. Methods. A case-control longitudinal study was performed that involved 30 adult patients with laboratory-confirmed Chikungunya fever. Their profiles of clinical disease, viral load, and immune mediators were investigated. Results. When patients were segregated into high viral load and low viral load groups during the acute phase, those with high viremia had lymphopenia, lower levels of monocytes, neutrophilia, and signs of inflammation. The high viral load group was also characterized by a higher production of pro-inflammatory cytokines, such as interferon-α and interleukin (IL)–6, during the acute phase. As the disease progressed to the chronic phase, IL-17 became detectable. However, persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony-stimulating factor, whereas patients who recovered fully had high levels of Eotaxin and hepatocyte growth factor. Conclusions. The level of CHIKV viremia during the acute phase determined specific patterns of pro-inflammatory cytokines, which were associated with disease severity. At the chronic phase, levels of IL-6, and granulocyte macrophage colony-stimulating factor found to be associated with persistent arthralgia provide a possible explanation for the etiology of arthralgia that plagues numerous CHIKV-infected patients. PMID:21288813

  14. Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

    Science.gov (United States)

    Rosen, Lindsey B; Rocha Pereira, Nuno; Figueiredo, Cristóvão; Fiske, Lauren C; Ressner, Roseanne A; Hong, Julie C; Gregg, Kevin S; Henry, Tracey L; Pak, Kirk J; Baumgarten, Katherine L; Seoane, Leonardo; Garcia-Diaz, Julia; Olivier, Kenneth N; Zelazny, Adrian M; Holland, Steven M; Browne, Sarah K

    2015-04-01

    Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF activity.

    Directory of Open Access Journals (Sweden)

    Gözde Isik

    Full Text Available HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs that target the envelope glycoprotein complex (Env. An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed Env(GM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized Env(GM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric Env(GM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins.

  16. Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia

    NARCIS (Netherlands)

    Vellenga, E; UylDeGroot, CA; deWit, R; Keizer, HJ; Lowenberg, B; tenHaaft, MA; deWitte, TJM; Verhagen, CAH; Stoter, GJ; Rutten, FFH; Mulder, NH; Smid, WM; deVries, EGE

    Purpose: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. Patients and Methods: One hundred thirty-four patients with a

  17. Fludarabine, cyclophosphamide and rituximab plus granulocyte macrophage colony-stimulating factor as frontline treatment for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Ferrajoli, Alessandra; Lerner, Susan; O'Brien, Susan; Wierda, William; Keating, Michael J; Faderl, Stefan

    2014-04-01

    Fludarabine, cyclophosphamide and rituximab (FCR), the standard of care for the frontline treatment of patients with chronic lymphocytic leukemia (CLL), is associated with a high rate of neutropenia and infectious complications. Granulocyte macrophage colony-stimulating factor (GM-CSF) reduces myelosuppression and can potentiate rituximab activity. We conducted a clinical trial combining GM-CSF with FCR for frontline treatment of 60 patients with CLL. Eighty-six percent completed all six courses and 18% discontinued GM-CSF for toxicity: grade 3-4 neutropenia was observed in 30% of cycles, and severe infections in 16% of cases. The overall response rate was 100%. Both median event-free survival (EFS) and overall survival (OS) have not been reached. Longer EFS was associated with favorable cytogenetics. GM-CSF led to a lower frequency of infectious complications than in the historical FCR group, albeit similar EFS and OS.

  18. Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis)

    KAUST Repository

    Sugumar, Thennarasu

    2013-06-25

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF. Buffalo GM-CSF has been compared with 17 mammalian GM-CSFs using multiple sequence alignment and phylogenetic tree. Three-dimensional model for buffalo GM-CSF and human receptor complex was built using homology modelling to study cross-reactivity between two species. Detailed analysis was performed to study GM-CSF interface and various interactions at the interface. © 2013 John Wiley & Sons Ltd.

  19. Granulocyte-macrophage colony-stimulating factor increases tumor growth and angiogenesis directly by promoting endothelial cell function and indirectly by enhancing the mobilization and recruitment of proangiogenic granulocytes.

    Science.gov (United States)

    Zheng, Qiaowei; Li, Xueqian; Cheng, Xiaoliang; Cui, Ting; Zhuo, Yingcheng; Ma, Wenbin; Zhao, Xue; Zhao, Peipei; Liu, Xuanlin; Feng, Weiyi

    2017-02-01

    Granulocyte-macrophage colony-stimulating factor has been widely used as an adjuvant therapy for cancer patients exhibiting myelosuppression induced by chemotherapy or radiotherapy. However, the effects of granulocyte-macrophage colony-stimulating factor on tumor growth, as well as its precise mechanism, are still controversial due to inconsistent evidence. This study investigated the effect of exogenous granulocyte-macrophage colony-stimulating factor on the growth of B16 melanoma, S180 sarcoma, and U14 cervical carcinoma in mice. The angiogenesis and recruitment of bone-marrow-derived cells were analyzed in tumor tissues. Interactions among granulocyte-macrophage colony-stimulating factor, bone-marrow-derived cells, and B16 tumor cells were investigated in vitro. Proangiogenic types of bone-marrow-derived cells in blood were assessed both in vivo and in vitro. The results showed that granulocyte-macrophage colony-stimulating factor markedly facilitated the growth of B16 and S180 tumors, but not U14 tumors. Granulocyte-macrophage colony-stimulating factor increased the densities of blood vessels and the number of bone-marrow-derived cells in B16 tumor tissues. The granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor cell proliferation was mediated by bone-marrow-derived cells in vitro. Meanwhile, a distinct synergistic effect on endothelial cell function between granulocyte-macrophage colony-stimulating factor and bone-marrow-derived cells was observed. After separating two types of bone-marrow-derived cells, granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor growth and angiogenesis in vivo was mediated by proangiogenic cells in granulocytes, but not monocytes, with CD11b+, vascular endothelial growth factor receptor 2, and C-X-C chemokine receptor 4 granulocytes possibly involved. These data suggest that granulocyte-macrophage colony-stimulating factor contributes to the growth and angiogenesis of certain types

  20. Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells duringMycobacterium tuberculosisInfection.

    Science.gov (United States)

    Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

    2017-10-24

    Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune

  1. The optimal use of granulocyte macrophage colony stimulating factor in radiation induced mucositis in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Patni Nidhi

    2005-01-01

    Full Text Available Objective: Evaluation of response of granulocyte macrophage colony stimulating factor (GM-CSF on acute radiation toxicity profile in head and neck squamous cell carcinoma. Methods and Materials: Thirty three patients with proven stage I or II head & neck carcinoma received conventional external beam radiation therapy. Out of these, six patients received postoperative adjuvant therapy while remaining 27 received definitive RT. Patients were given 100 mcg GM-CSF subcutaneously per day along with radiation after they developed grade 2 mucositis and /or grade 2 dysphagia and / or complained of moderate pain. GM-CSF was administered till there was a subjective relief or objective response. Patients were evaluated for oral ulceration, swallowing status, pain and weight loss. Response to the treatment and patient outcome was assessed. Results: There was a decreased severity of mucositis and dysphagia in the evaluated patients. None of the patients suffered severe pain or required opioids. The mean weight loss was only 1.94%. Minimal side effects were experienced with GM-CSF. Conclusions: GM-CSF reduces the severity of acute side effects of radiation therapy thereby allowing completion of the treatment without interruption. Its remarkable response needs to be evaluated further in large randomized trials. The time of initiation and cessation of GM-CSF during radiation therapy and the required dose needs to be established.

  2. Increased secretion of granulocyte-macrophage colony-stimulating factor in mucosal lesions of inflammatory bowel disease.

    Science.gov (United States)

    Noguchi, M; Hiwatashi, N; Liu, Z X; Toyota, T

    2001-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 transmit a same signal needed for growth and activation in granulocytes and macrophages, because these receptors utilize a common beta chain. Little is known about growth factors for intestinal myeloid cells in lesions of inflammatory bowel disease (IBD). To find out whether GM-CSF is produced by the intestinal cells in IBD patients and controls. We measured levels of GM-CSF, tumor necrosis factor (TNF), and IL-3 in the media of organ culture and lamina propria mononuclear cells (LPMCs) culture of colonic mucosa from the patients with IBD. Next, we have investigated GM-CSF production of colonic epithelial cell lines. Spontaneous secretion of GM-CSF was increased in inflamed mucosa, while secretion of IL-3 was not detected. Release of GM-CSF was enhanced in LPMCs from inflamed mucosa. Mucosal GM-CSF production was correlated to TNF-alpha production. Colonic epithelial cell line and T cell produced GM-CSF with superantigen stimulation. We revealed pivotal production of GM-CSF but not IL-3 in intestinal lesion of IBD. Increased secretion of GM-CSF might lead to chronic gut inflammation. Copyright 2001 S. Karger AG, Basel

  3. Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-kappaB ligand, and matrix metalloproteinases and drives bone and cartilage pathology in experimental arthritis: rationale for combination therapy in rheumatoid arthritis

    NARCIS (Netherlands)

    Nieuwenhuijze, A.E. van; Loo, F.A.J. van de; Walgreen, B.; Bennink, M.; Helsen, M.; Bersselaar, L. van den; Wicks, I.P.; Berg, W.B. van den; Koenders, M.I.

    2015-01-01

    INTRODUCTION: Type 17 T helper cells and interleukin (IL)-17 play important roles in the pathogenesis of human and murine arthritis. Although there is a clear link between IL-17 and granulocyte macrophage colony-stimulating factor (GM-CSF) in the inflammatory cascade, details about their interaction

  4. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R; Robinson, Harriet L

    2012-11-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection.

  5. Granulocyte macrophage colony-stimulating factor treatment results in recovery of motor function after white matter damage in mice.

    Science.gov (United States)

    Theoret, Jennifer K; Jadavji, Nafisa M; Zhang, Min; Smith, Patrice D

    2016-01-01

    Clinical stroke usually results from a cerebral ischaemic event, and is frequently a debilitating condition with limited treatment options. A significant proportion of clinical strokes result from specific damage to the subcortical white matter (SWM), but currently there are few animal models available to investigate the pathogenesis and potential therapeutic strategies to promote recovery. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine that has been previously shown to promote neuroprotective effects after brain damage; however, the mechanisms mediating this effect are not known. Here, it is reported that GM-CSF treatment results in dramatic functional improvement in a white matter model of stroke in mice. SWM stroke was induced in mice by unilateral injections of the vasoconstrictor, endothelin-1 (ET-1). The results reveal that ET-1-induced stroke impairs skilled motor function on the single pellet-reaching task and results in forelimb asymmetry, in adult mice. Treatment with GM-CSF, after stroke, restores motor function and abolishes forelimb asymmetry. The results also indicate that GM-CSF promotes its effects by activating mammalian target of rapamycin signalling mechanisms in the brain following stroke injury. Additionally, a significant increase in GM-CSF receptor expression was found in the ipsilateral hemisphere of the ET-1-injected brain. Taken together, the present study highlights the use of an under-utilized mouse model of stroke (using ET-1) and suggests that GM-CSF treatment can attenuate ET-1-induced functional deficits. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Acute granulocyte macrophage-colony stimulating factor treatment modulates neuroinflammatory processes and promotes tactile recovery after spinal cord injury.

    Science.gov (United States)

    Thomaty, Sandie; Pezard, Laurent; Xerri, Christian; Brezun, Jean-Michel

    2017-05-04

    Neuroinflammation is known to play a key role in the prognosis of functional recovery after spinal cord injury (SCI). The involvement of microglial and mast cells in early and late stages of inflammation has been receiving increasing attention. This study was aimed at determining the influence of a pro-inflammatory cytokine, the granulocyte macrophage-colony stimulating factor (GM-CSF), on microglia and mast cell activation, glial scar formation and functional recovery following SCI. Rats were randomly injected with saline or GM-CSF one hour after a C4-C5 medio-lateral hemisection. To assess functional impairment and recovery, the rats were subjected to sensorimotor tasks for one month. Then, responses evoked by forepaw stimulation in the primary somatosensory cortex were recorded. We also quantified the changes in GM-CSF, IL-1β, IL-6 and BDNF levels, the gliosis and lesion volume as well as microglial and mast cell density, and mast cell surface. Our findings show that GM-CSF promotes cortical reactivation and recovery of tactile abilities, whereas it does not influence motor performances. A transient decrease in pro-inflammatory cytokines after GM-CSF treatment was also observed, whereas the endogenous GM-CSF level was unchanged. While the beneficial role of GM-CSF in reducing glial scar is confirmed, our findings reveal that neuroinflammatory events mediated by microglial and mast cells as well as the alteration of IL-1β and IL-6 levels are paralleled with an improvement in tactile recovery. These mechanisms could limit the duration and intensity of homeostatic imbalance and promote the plasticity of spared tissues. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years

    Science.gov (United States)

    Marlow, Neil; Morris, Timothy; Brocklehurst, Peter; Carr, Robert; Cowan, Frances M; Patel, Nishma; Petrou, Stavros; Redshaw, Maggie E; Modi, Neena; Dore, Caroline

    2013-01-01

    Objective The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal sepsis-free survival. Patients and methods 280 babies born <31 weeks of gestation and SGA were entered into the trial. Outcome was determined at 2 years to determine neurodevelopmental and general health outcomes, including economic costs. Results The authors found no significant differences in health outcomes or health and social care costs between the trial groups. In the GM-CSF arm, 87 of 134 (65%) babies survived to 2 years without severe disability compared with 87 of 131 (66%) controls (RR: 1·0, 95% CI 0·8 to 1·2). Marginally, more children receiving GM-CSF were reported to have cough (RR 1·7, 95% CI 1·1 to 2·6) and had signs of chronic respiratory disease (Harrison's sulcus; RR 2·0, 95% CI 1·0 to 3·9) though this was not reflected in bronchodilator use or need for hospitalisation for respiratory disease. Overall, the rate of neurologic abnormality (7%–9%) was similar but mean overall developmental scores were lower than expected for gestational age. Conclusions The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse outcomes at 2 years of age. The apparent excess of developmental impairment in the entire PROGRAMS cohort, without corresponding increase in neurological abnormality, may represent diffuse brain injury attributable to intrauterine growth restriction. PMID:22542709

  8. Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma.

    Science.gov (United States)

    Hoeller, Christoph; Michielin, Olivier; Ascierto, Paolo A; Szabo, Zsolt; Blank, Christian U

    2016-09-01

    Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte-macrophage colony-stimulating factor (GM-CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have been mixed, and while GM-CSF has the potential to promote anti-tumor responses, some preclinical data suggest that GM-CSF may sometimes promote tumor growth. GM-CSF has not been approved as a melanoma treatment. We undertook a systematic literature review of studies of GM-CSF in patients with advanced melanoma (stage IIIB-IV). Of the 503 articles identified, 26 studies met the eligibility criteria. Most studies investigated the use of GM-CSF in combination with another treatment, such as peptide vaccines or chemotherapy, or as an adjuvant to surgery. Some clinical benefit was reported in patients who received GM-CSF as an adjuvant to surgery, or in combination with other treatments. In general, outcomes for patients receiving peptide vaccines were not improved with the addition of GM-CSF. GM-CSF may be a valuable therapeutic adjuvant; however, further studies are needed, particularly head-to-head comparisons, to confirm the optimal dosing regimen and clinical effectiveness in patients with advanced melanoma.

  9. In vivo kinetics of sup 111 Indium-labelled autologous granulocytes following i. v. administration of granulocyte-macrophage colony-stimulating factor (GM-CSF)

    Energy Technology Data Exchange (ETDEWEB)

    Hovgaard, D.; Mortensen, B.T.; Nissen, N.I. (Department of Hematology, Rigshospitalet, Copenhagen (Denmark)); Schifter, S.; Raboel, A. (Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen (Denmark))

    1992-01-01

    Administration of both glycosylated and non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces an immediate transient granulocytopenia of 1-3 hours' duration. In order to explore this phenomenon, granulocytes were labelled with {sup 111}Indium and the effect on the kinetics of granulocytes after administration of rhGM-CSF was studied in 10 previously untreated patients with malignant lymphoma. For both types and doses of rhGM-CSF, a significant and dramatic accumulation of the {sup 111}Indium-labelled granulocytes was observed in the lung within a few minutes after i.v. injection of rhGM-CSF. The accumulation of radioactivity coincided with the pronounced and transient granulocytopenia in peripheral blood. The {sup 111}Indium-labelled granulocytes later reappeared in the peripheral blood, indicating reversible pulmonary vascular margination of the granulocytes. Half-life of labelled granulocytes after reappearance was comparable to half-life values under normal conditions. The transient accumulation of granulocytes in the pulmonary vessels seems not to be of clinical importance in the management of patients, but it may to some degree explain previously described side-effects, such as transient hypoxemia (''first-dose'' reaction) following administration of rhGM-CSF. (au).

  10. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

    Directory of Open Access Journals (Sweden)

    José Mordoh

    2017-05-01

    Full Text Available The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM patients (pts after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663. Thirty-one pts were randomized to the CSF-470 vaccine (n = 20 or to the IFN-α2b arm (n = 11. During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS for CSF-470 was observed (p = 0.022. Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11, hepatic (2/11, and cardiac (1/11 toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001. Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

  11. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  12. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Directory of Open Access Journals (Sweden)

    Chang Rae Rho

    Full Text Available Granulocyte-macrophage colony-stimulating factor (GM-CSF is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs. We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF. An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml. MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  13. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Science.gov (United States)

    Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

    2015-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  14. Cytosine arabinoside reduces the numbers of granulocyte macrophage colony forming cells (GM-CFC) and high proliferative potential colony forming cells (HPP-CFC) in vivo in mice.

    Science.gov (United States)

    Teleka, Stanley; Chijuwa, Alexander; Senga, Edward; Chisi, John E

    2011-12-01

    Cytosine arabinoside (Ara-C) is an S-phase specific cytotoxic drug used in the treatment of malignancies. It is converted to Cytosine Arabinoside triphosphate (Ara-CTP) in the cell. Cytosine Arabinoside triphosphate, reversibly displaces deoxy cytidine triphosphate from DNA polymerase for incorporation into DNA. This process leads to cell death. To investigate the in vivo effects of Ara-C on the Granulocyte Macrophage Colony Forming Cells (GM-CFC) and High Proliferative Potential Colony Forming Cells (HPP-CFC) respectively in mice. Ara-C (150mg/kg) was administered intraperitoneally (i.p) once to mice and bone marrow cells sampled on days 1, 3 and 6. Ara-C reduced the numbers of both GM-CFC and HPP-CFC in the bone marrow. HPP-CFCs were initially more sensitive to Ara-C treatment than GM-CFCs. In the six days after treatment the effect on GM-CFC persisted, while there was a partial recovery in the number of HPP-CFCs. It is possible that Ara-C disturbs the stem cells niche by damaging the stromal cells of the bone marrow microenvironment. This would result in derangement of HPP-CFC proliferation.

  15. Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis.

    Science.gov (United States)

    Nascimento, Magda Paula Pereira do; Bannwart, Camila Ferreira; Nakaira-Takahagi, Erika; Peraçoli, Maria Terezinha Serrão

    2011-09-01

    Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

  16. Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

    Directory of Open Access Journals (Sweden)

    Magda Paula Pereira do Nascimento

    2011-09-01

    Full Text Available Multinucleated giant cells (MGC are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF in association with other cytokines such as interferon-gamma (IFN-γ, tumour necrosis factor-alpha, interleukin (IL-10 or transforming growth factor beta (TGF-β1 on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg. The generation of MGC was determined by fusion index (FI and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18. The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

  17. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

    NARCIS (Netherlands)

    Eertwegh, A.J. van den; Versluis, J.; van den Berg, H.P.; Santegoets, S.J.; van Moorselaar, R.J.; van der Sluis, T.M.; Gall, H.E.; Harding, T.C.; Jooss, K.; Lowy, I.; Pinedo, H.M.; Scheper, R.J.; Stam, A.G.; Blomberg, B.M. von; Gruijl, T.D. de; Hege, K.; Sacks, N.; Gerritsen, W.R.

    2012-01-01

    BACKGROUND: The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte

  18. Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-κB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line

    Directory of Open Access Journals (Sweden)

    Ana Luísa Vital

    2003-01-01

    Full Text Available Aims: Nitric oxide (NO has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF in a mouse fetal skin dendritic cell line.

  19. Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony-stimulating factor

    Energy Technology Data Exchange (ETDEWEB)

    Tavassoli, M.; Konno, M.; Shiota, Y.; Omoto, E.; Minguell, J.J.; Zanjani, E.D.

    1991-04-01

    To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF-treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

  20. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte?macrophage colony?stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma

    OpenAIRE

    Andtbacka, Robert H. I.; Agarwala, Sanjiv S.; Ollila, David W.; Hallmeyer, Sigrun; Milhem, Mohammed; Amatruda, Thomas; Nemunaitis, John J; Harrington, Kevin J; Chen, Lisa; Shilkrut, Mark; Ross, Merrick; Howard L. Kaufman

    2016-01-01

    Abstract Background Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ?6 months) compared with subcutaneous granulocyte?macrophage colony?stimulating factor (GM?CSF). Methods Retrospective review of OPTiM identified patients with cutaneous head a...

  1. Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity

    Science.gov (United States)

    Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

    1993-04-01

    To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4^+ and CD8^+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

  2. Diversity of Interferon γ and Granulocyte-Macrophage Colony-Stimulating Factor in Restoring Immune Dysfunction of Dendritic Cells and Macrophages During Polymicrobial Sepsis

    Science.gov (United States)

    Flohé, Stefanie B; Agrawal, Hemant; Flohé, Sascha; Rani, Meenakshi; Bangen, Jörg M; Schade, F Ulrich

    2008-01-01

    The development of immunosuppression during polymicrobial sepsis is associated with the failure of dendritic cells (DC) to promote the polarization of T helper (Th) cells toward a protective Th1 type. The aim of the study was to test potential immunomodulatory approaches to restore the capacity of splenic DC to secrete interleukin (IL) 12 that represents the key cytokine in Th1 cell polarization. Murine polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Splenic DC were isolated at different time points after CLP or sham operation, and stimulated with bacterial components in the presence or absence of neutralizing anti-IL-10 antibodies, murine interferon (IFN) γ, and/or granulocyte macrophage colony-stimulating factor (GM-CSF). DC from septic mice showed an impaired capacity to release the pro-inflammatory and Th1-promoting cytokines tumor necrosis factor α, IFN-γ, and IL-12 in response to bacterial stimuli, but secreted IL-10. Endogenous IL-10 was not responsible for the impaired IL-12 secretion. Up to 6 h after CLP, the combined treatment of DC from septic mice with IFN-γ and GM-CSF increased the secretion of IL-12. Later, DC from septic mice responded to IFN-γ and GM-CSF with increased expression of the co-stimulatory molecule CD86, while IL-12 secretion was no more enhanced. In contrast, splenic macrophages from septic mice during late sepsis responded to GM-CSF with increased cytokine release. Thus, therapy of sepsis with IFN-γ/GM-CSF might be sufficient to restore the activity of macrophages, but fails to restore DC function adequate for the development of a protective Th1-like immune response. PMID:18297128

  3. Diversity of interferon gamma and granulocyte-macrophage colony-stimulating factor in restoring immune dysfunction of dendritic cells and macrophages during polymicrobial sepsis.

    Science.gov (United States)

    Flohé, Stefanie B; Agrawal, Hemant; Flohé, Sascha; Rani, Meenakshi; Bangen, Jörg M; Schade, F Ulrich

    2008-01-01

    The development of immunosuppression during polymicrobial sepsis is associated with the failure of dendritic cells (DC) to promote the polarization of T helper (Th) cells toward a protective Th1 type. The aim of the study was to test potential immunomodulatory approaches to restore the capacity of splenic DC to secrete interleukin (IL) 12 that represents the key cytokine in Th1 cell polarization. Murine polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Splenic DC were isolated at different time points after CLP or sham operation, and stimulated with bacterial components in the presence or absence of neutralizing anti-IL-10 antibodies, murine interferon (IFN) gamma, and/or granulocyte macrophage colony-stimulating factor (GM-CSF). DC from septic mice showed an impaired capacity to release the pro-inflammatory and Th1-promoting cytokines tumor necrosis factor alpha, IFN-gamma, and IL-12 in response to bacterial stimuli, but secreted IL-10. Endogenous IL-10 was not responsible for the impaired IL-12 secretion. Up to 6 h after CLP, the combined treatment of DC from septic mice with IFN-gamma and GM-CSF increased the secretion of IL-12. Later, DC from septic mice responded to IFN-gamma and GM-CSF with increased expression of the co-stimulatory molecule CD86, while IL-12 secretion was no more enhanced. In contrast, splenic macrophages from septic mice during late sepsis responded to GM-CSF with increased cytokine release. Thus, therapy of sepsis with IFN-gamma/GM-CSF might be sufficient to restore the activity of macrophages, but fails to restore DC function adequate for the development of a protective Th1-like immune response.

  4. A Lethally Irradiated Allogeneic Granulocyte-Macrophage Colony Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Adenocarcinoma: A Phase II Trial of Safety, Efficacy, and Immune Activation

    Science.gov (United States)

    Lutz, Eric; Yeo, Charles J.; Lillemoe, Keith D.; Biedrzycki, Barbara; Kobrin, Barry; Herman, Joseph; Sugar, Elizabeth; Piantadosi, Steven; Cameron, John L.; Solt, Sara; Onners, Beth; Tartakovsky, Irena; Choi, Miri; Sharma, Rajni; Illei, Peter B.; Hruban, Ralph H.; Abrams, Ross A.; Le, Dung; Jaffee, Elizabeth; Laheru, Dan

    2011-01-01

    Purpose Surgical resection provides the only possibility of cure for pancreas cancer. A standard adjuvant approach has not been established. We tested the safety and efficacy of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapy administered in patients with resected pancreatic adenocarcinoma. Patients and Methods A single institution phase II study of 60 patients with resected pancreatic adenocarcinoma was performed. Each immunotherapy treatment consisted of a total of 5 × 108 GM-CSF-secreting cells distributed equally among 3 lymph node regions. The first immunotherapy treatment was administered 8 to 10 weeks after surgical resection. Subsequently, patients received 5-FU based chemoradiation. Patients who remained disease-free after completion of chemoradiotherapy received treatments 2 to 4, each 1 month apart. A fifth and final booster was administered 6 months after the fourth immunotherapy. The primary endpoint was disease free survival and secondary endpoints were overall survival and toxicity, and the induction of mesothelin-specific T cell responses. Results The median disease-free survival is 17.3 months (95% CI, 14.6–22.8) with median survival of 24.8 months (95% CI, 21.2–31.6). The administration of immunotherapy was well tolerated. In addition, the postimmunotherapy induction of mesothelin-specific CD8+ T cells in HLA-A1+ and HLA-A2+ patients correlates with disease-free survival. Conclusions An immunotherapy approach integrated with chemoradiation is safe and demonstrates an overall survival that compares favorably with published data for resected pancreas cancer. These data suggest additional boost immunotherapies given at regular intervals beyond 1 year postsurgery should be tested in future studies, and provide the rationale for conducting a multicenter phase II study. PMID:21217520

  5. Competent antigen-presenting cells are generated from the long-term culture of splenocytes with granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Ryu, Seul Hye; Na, Hye Young; Sohn, Moah; Choi, Wanho; In, Hyunju; Shin, Hyun Soo; Choi, Jae-Hoon; Park, Chae Gyu

    2017-08-01

    Dendritic cells (DCs) are routinely produced from the culture of mouse bone marrow (BM) with granulocyte-macrophage colony-stimulating factor (GM-CSF) within a period of 10days. Although splenic extramedullary myelopoiesis was suggested to occur under the influence of GM-CSF, the hematopoietic outcome of splenic culture with GM-CSF has not been scrutinized. We have cultured mouse splenocytes with GM-CSF for an extended period of time, where we discovered that the CD11b⁺CD11c⁺ cells began to proliferate prominently after 10days and their number increased until the 4th week of the culture. In parallel experiments, FMS-like tyrosine kinase 3 (FLT3) and its ligand, FLT3L, were not found to influence the culture of splenocytes. Like DCs in the culture of BM with GM-CSF, a distinct population of CD11b⁺CD11c⁺MHC IIhi cells was readily identified as DCs in the long-term culture of splenocytes. After being isolated and plated overnight the CD11b⁺CD11c⁺MHC IIhi cells exhibited non-adherent dendritic morphology, while the other CD11b⁺CD11c⁺ cells became adherent. Besides, these CD11b⁺CD11c⁺MHC IIhi cells possessed relatively weak endocytic and phagocytic abilities but displayed strong antigen-presenting capacities, revealing DC-like characteristics; in contrast, the other CD11b⁺CD11c⁺ cells showed strong endocytosis and phagocytosis of antigens but were poor at antigen presentation, indicating macrophage-like traits. Therefore, we demonstrated that phenotypically as well as functionally genuine DCs are generated in the long-term culture of splenocytes with GM-CSF. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Zheng, Lei; Edil, Barish H; Soares, Kevin C; El-Shami, Khaled; Uram, Jennifer N; Judkins, Carol; Zhang, Zhe; Onners, Beth; Laheru, Daniel; Pardoll, Drew; Jaffee, Elizabeth M; Schulick, Richard D

    2014-11-01

    Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine. A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer. A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies. This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.

  7. Granulocyte Macrophage Colony-Stimulating Factor–Activated CD39+/CD73+ Murine Monocytes Modulate Intestinal Inflammation via Induction of Regulatory T CellsSummary

    Directory of Open Access Journals (Sweden)

    Toni Weinhage

    2015-07-01

    Full Text Available Background & Aims: Granulocyte macrophage colony-stimulating factor (GM-CSF treatment induces clinical response in patients with active Crohn’s disease. To explore whether monocytes mediate GM-CSF effects in vivo, we used a mouse model of chronic colitis induced by dextran sulfate sodium (DSS. Methods: Murine bone marrow-derived monocytes were activated with GM-CSF in vitro, and gene expression, phenotype, and function of GM-CSF-activated monocytes (GMaM were analyzed. Therapeutic effects of GMaM were assessed in a model of chronic colitis induced by repeated cycles of DSS. Monocytes were administered intravenously and their immunomodulatory functions were evaluated in vivo by clinical monitoring, histology, endoscopy, immunohistochemistry, and expression of inflammatory markers in the colon. The distribution of injected monocytes in the intestine was measured by in vivo imaging. Results: GMaM expressed significantly higher levels of anti-inflammatory molecules. Production of reactive oxygen species was also increased while phagocytosis and adherence were decreased. GMaM up-regulated CD39 and CD73, which allows the conversion of adenosine triphosphate into adenosine and coincided with the induction of Foxp3+ (forkhead-box-protein P3 positive regulatory T cells (Treg in cocultures of GMaM and naive T cells. In chronic DSS-induced colitis, adoptive transfer of GMaM led to significant clinical improvement, as demonstrated by reduced weight loss, inflammatory infiltration, ulceration, and colon shrinkage. As GMaM migrated faster and persisted longer in the inflamed intestine compared with control monocytes, their presence induced Treg generation in vivo. Conclusions: GM-CSF leads to specific monocyte activation that modulates experimental colitis via mechanisms that include the induction of Treg. We demonstrate a possible mechanism of Treg induction through CD39 and CD73 expression on monocytes. Keywords: Adaptive Immunity

  8. Priming of mouse macrophages with the macrophage colony-stimulating factor (CSF-1) induces a variety of pathways that regulate expression of the interleukin 6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm) genes.

    Science.gov (United States)

    Kamdar, S J; Fuller, J A; Nishikawa, S I; Evans, R

    1997-08-25

    Recent data have indicated that resident mouse peritoneal macrophages (PMo) transcribed the interleukin 6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm) genes in response to stimulation with the monocyte-macrophage colony-stimulating factor (CSF-1) but only Il6 mRNA was translated into secreted protein. In this paper, we extend these observations. It is shown that resident PMo incubated with protein kinase (PK)C inhibitors, staurosporine (SP) and its derivative GF109203-X, showed a several fold increase in the levels of Il6 mRNA in control and CSF-1-primed PMo and a parallel release of large amounts of protein. In contrast, SP was shown to have no effect on the release of GM-CSF from control or CSF-1-primed PMo, although it increased by approximately twofold the amount of Csfgm mRNA in CSF-1-primed Mo. When SP was added 4 h after CSF-1 priming to block CSF-1-induced protein kinase pathways, an increased amount of IL-6 release was again seen but without any increase in Il6 mRNA levels. Under these conditions, Csfgm gene expression was relatively unaffected. Activation of PKC by phorbol myristate acetate (PMA) also resulted in increased Il6 gene expression by control and CSF-1-primed PMo. PMA had no apparent effect on Csfgm transcription but appeared to influence translation at a low level, as measured by the release of small amounts of GM-CSF protein. The addition of lipopolysaccharide (LPS) to CSF-1-primed PMo resulted in a synergistic increase in the expression of both genes at the levels of transcription and protein release. The addition of SP to CSF-1-primed Mo before LPS, however, further enhanced IL-6 release but not GM-CSF release from the cells. The data indicate that CSF-1-priming drives a number of pathways involved in the regulation of expression of both genes and renders PMo highly susceptible to appropriate secondary stimulatory agents that transform the PMo into secretory inflammatory cells.

  9. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma.

    Science.gov (United States)

    Andtbacka, Robert H I; Agarwala, Sanjiv S; Ollila, David W; Hallmeyer, Sigrun; Milhem, Mohammed; Amatruda, Thomas; Nemunaitis, John J; Harrington, Kevin J; Chen, Lisa; Shilkrut, Mark; Ross, Merrick; Kaufman, Howard L

    2016-12-01

    Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc.

  10. Immune-enhancing effect of nano-DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Zhai, Yongzhen; Zhou, Yan; Li, Ximei; Feng, Guohe

    2015-07-01

    Plasmid-encoded granulocyte-macrophage colony-stimulating factor (GM‑CSF) is an adjuvant for genetic vaccines; however, how GM-CSF enhances immunogenicity remains to be elucidated. In the present study, it was demonstrated that injection of a plasmid encoding the premembrane (prM) and envelope (E) protein of Japanese encephalitis virus and mouse GM-CSF (pJME/GM-CSF) into mouse muscle recruited large and multifocal conglomerates of macrophages and granulocytes, predominantly neutrophils. During the peak of the infiltration, an appreciable number of immature dendritic cells (DCs) appeared, although no T and B-cells was detected. pJME/GM-CSF increased the number of splenic DCs and the expression of major histocompatibility complex class II (MHCII) on splenic DC, and enhanced the antigenic capture, processing and presentation functions of splenic DCs, and the cell-mediated immunity induced by the vaccine. These findings suggested that the immune-enhancing effect by pJME/GM-CSF was associated with infiltrate size and the appearance of integrin αx (CD11c)+cells. Chitosan-pJME/GM-CSF nanoparticles, prepared by coacervation via intramuscular injection, outperformed standard pJME/GM-CSF administrations in DC recruitment, antigen processing and presentation, and vaccine enhancement. This revealed that muscular injection of chitosan‑pJME/GM-CSF nanoparticles may enhance the immunoadjuvant properties of GM-CSF.

  11. Nicotine can skew the characterization of the macrophage type-1 (M{Phi}1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the M{Phi}2 phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Yanagita, Manabu; Kobayashi, Ryohei [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan)

    2009-10-09

    Macrophages (M{Phi}s) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that M{Phi}s can be divided into proinflammatory M{Phi}s (M{Phi}1) and anti-inflammatory M{Phi}s (M{Phi}2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of M{Phi}1. Granulocyte-macrophage colony-stimulating factor-driven M{Phi}1 with nicotine (Ni-M{Phi}1) showed the phenotypic characteristics of M{Phi}2. Like M{Phi}2, Ni-M{Phi}1 exhibited antigen-uptake activities. Ni-M{Phi}1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with M{Phi}1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated M{Phi}1, whereas Ni-M{Phi}1 reduced T cell proliferation and inhibited IFN-{gamma} production by T cells. These results suggest that nicotine can change the functional characteristics of M{Phi} and skew the M{Phi}1 phenotype to M{Phi}2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

  12. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial.

    Science.gov (United States)

    Harrington, Kevin J; Andtbacka, Robert Hi; Collichio, Frances; Downey, Gerald; Chen, Lisa; Szabo, Zsolt; Kaufman, Howard L

    2016-01-01

    Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB-IVM1a disease. The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. Among 249 evaluated patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; Ptalimogene laherparepvec arm (40.5% versus 2.3%; Ptalimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments. The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated.

  13. Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma.

    Science.gov (United States)

    Spitler, Lynn E; Cao, Huynh; Piironen, Timo; Whiteside, Theresa L; Weber, Robert W; Cruickshank, Scott

    2017-04-01

    We investigated the development of binding and neutralizing antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biological effects. Fifty-three patients with high-risk melanoma that had been surgically excised were treated with GM-CSF, 125 μg/m daily for 14 days every 28 days for 1 year after surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on study days 155 and 351. Blood draws for testing biological effects were keyed to GM-CSF administration: days 0 (before), 15 (after 14 d on GM-CSF), 29 (after 14 d off GM-CSF), 155, and 351 (after 14 d on GM-CSF in the sixth and 13th cycle of treatment). Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell count, percent eosinophils, or neopterin levels engendered by GM-CSF administration was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies. Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biological effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials.

  14. Mycobacterium tuberculosis-induced expression of granulocyte-macrophage colony stimulating factor is mediated by PI3-K/MEK1/p38 MAPK signaling pathway

    Directory of Open Access Journals (Sweden)

    Jang-Eun Cho

    2013-04-01

    Full Text Available Members of the colony stimulating factor cytokine family playimportant roles in macrophage activation and recruitment toinflammatory lesions. Among them, granulocyte-macrophagecolony stimulating factor (GM-CSF is known to be associatedwith immune response to mycobacterial infection. However,the mechanism through which Mycobacterium tuberculosis(MTB affects the expression of GM-CSF is poorly understood.Using PMA-differentiated THP-1 cells, we found that MTBinfection increased GM-CSF mRNA expression in a dosedependentmanner. Induction of GM-CSF mRNA expressionpeaked 6 h after infection, declining gradually thereafter andreturning to its basal levels at 72 h. Secretion of GM-CSFprotein was also elevated by MTB infection. The increase inmRNA expression and protein secretion of GM-CSF caused byMTB was inhibited in cells treated with inhibitors of p38MAPK, mitogen-activated protein kinase kinase (MEK-1, andPI3-K. These results suggest that up-regulation of GM-CSF byMTB is mediated via the PI3-K/MEK1/p38 MAPK-associatedsignaling pathway. [BMB Reports 2013; 46(4: 213-218

  15. Unopposed Production of Granulocyte-Macrophage Colony-Stimulating Factor by Tumors Inhibits CD8+ T Cell Responses by Dysregulating Antigen-Presenting Cell Maturation1

    OpenAIRE

    Bronte, Vincenzo; Chappell, Dale B.; Apolloni, Elisa; Cabrelle, Anna; Wang, Michael; Hwu, Patrick; Restifo, Nicholas P.

    1999-01-01

    Tumor cells gene-modified to produce GM-CSF potently stimulate antitumor immune responses, in part, by causing the growth and differentiation of dendritic cells (DC). However, GM-CSF-modified tumor cells must be γ-irradiated or they will grow progressively, killing the host. We observed that 23 of 75 (31%) human tumor lines and two commonly used mouse tumor lines spontaneously produced GM-CSF. In mice, chronic GM-CSF production by tumors suppressed Ag-specific CD8+ T cell responses. Interesti...

  16. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

    Directory of Open Access Journals (Sweden)

    Harrington KJ

    2016-11-01

    Full Text Available Kevin J Harrington,1 Robert HI Andtbacka,2 Frances Collichio,3 Gerald Downey,4 Lisa Chen,5 Zsolt Szabo,6 Howard L Kaufman7 1The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre, London, UK; 2Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; 3Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Amgen Ltd, Cambridge, UK; 5Amgen Inc, Thousand Oaks, CA, USA; 6Amgen GmbH, Zug, Switzerland; 7Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA Objectives: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704, talimogene laherparepvec significantly improved durable response rate (DRR versus granulocyte-macrophage colony-stimulating factor (GM-CSF in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a. Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease. Patients and methods: The patients were randomized (2:1 ratio to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR, OS, safety, benefit–risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. Results: Among 249 evaluated patients with stage IIIB–IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001. ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001, and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE and serious AEs were similar with both treatments. Conclusion

  17. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by female mouse bladder urothelial cells and expressed by the urothelium as an early response to lipopolysaccharides (LPS).

    Science.gov (United States)

    Li, Yan; Lu, Ming; Alvarez-Lugo, Lery; Chen, Gang; Chai, Toby C

    2017-04-01

    We studied in vitro and in vivo response of primary mouse bladder urothelial cells (mBUC) and bladder urothelium to lipopolysaccharides (LPS), focusing on granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. Female C57BL/6 mBUC were exposed for 12 hr to differing concentrations of LPS (100 ng/ml to 10 µg/ml). mBUC were also exposed to a single dose of LPS (1 µg/ml) for 3, 6, 12 hr. Neutralizing GM-CSF antibody (0.1 μg/ml) was used block GM-CSF activity in vitro. In vivo experiments were performed, whereby, LPS (1 mg/ml) was instilled intravesically and left to dwell for 30 min followed by harvest of bladder urothelium 3 to 18 hr later. ELISA measured GM-CSF. qPCR quantitated mRNA for GM-CSF, vascular endothelial growth factor-A (VEGF-A), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor α (TNF-α). RT-PCR was used to detect mRNA for GM-CSF, GM-CSFRα, and β in bladder tissues. Immunohistofluorescence and Western blots for GM-CSFRα were performed on bladder tissues. LPS induced a dose-dependent release of GM-CSF by mBUC. Mouse bladder urothelium did not express GM-CSF mRNA at baseline, but expressed GM-CSF mRNA 3 hr after in vivo LPS exposure, with GM-CSF mRNA expression disappearing 18 hr later. GM-CSFRα expression was confirmed in bladder urothelium. GM-CSF neutralizing antibody significantly diminished LPS-induced increases of VEGF and COX-2 mRNA expression. Urothelium and mBUC secreted GM-CSF as an early response to LPS. GM-CSF mediated downstream expression of VEGF and COX-2. Urothelial GM-CSF may function as a signaling mediator for both inflammation and pain transduction. Neurourol. Urodynam. 36:1020-1025, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation.

    Science.gov (United States)

    Bronte, V; Chappell, D B; Apolloni, E; Cabrelle, A; Wang, M; Hwu, P; Restifo, N P

    1999-05-15

    Tumor cells gene-modified to produce GM-CSF potently stimulate antitumor immune responses, in part, by causing the growth and differentiation of dendritic cells (DC). However, GM-CSF-modified tumor cells must be gamma-irradiated or they will grow progressively, killing the host. We observed that 23 of 75 (31%) human tumor lines and two commonly used mouse tumor lines spontaneously produced GM-CSF. In mice, chronic GM-CSF production by tumors suppressed Ag-specific CD8+ T cell responses. Interestingly, an inhibitory population of adherent CD11b(Mac-1)/Gr-1 double-positive cells caused the observed impairment of CD8+ T cell function upon direct cell-to-cell contact. The inhibitory cells were positive for some markers associated with Ag presenting cells, like F4/80, but were negative for markers associated with fully mature DC like DEC205, B7. 2, and MHC class II. We have previously reported that a similar or identical population of inhibitory "immature" APC was elicited after immunization with powerful recombinant immunogens. We show here that these inhibitory cells can be elicited by the administration of recombinant GM-CSF alone, and, furthermore, that they can be differentiated ex vivo into "mature" APC by the addition of IL-4 and GM-CSF. Thus, tumors may be able to escape from immune detection by producing "unopposed" GM-CSF, thereby disrupting the balance of cytokines needed for the maturation of fully functional DC. Further, CD11b/Gr-1 double-positive cells may function as "inhibitory" APC under the influence of GM-CSF alone.

  19. Unopposed Production of Granulocyte-Macrophage Colony-Stimulating Factor by Tumors Inhibits CD8+ T Cell Responses by Dysregulating Antigen-Presenting Cell Maturation1

    Science.gov (United States)

    Bronte, Vincenzo; Chappell, Dale B.; Apolloni, Elisa; Cabrelle, Anna; Wang, Michael; Hwu, Patrick; Restifo, Nicholas P.

    2008-01-01

    Tumor cells gene-modified to produce GM-CSF potently stimulate antitumor immune responses, in part, by causing the growth and differentiation of dendritic cells (DC). However, GM-CSF-modified tumor cells must be γ-irradiated or they will grow progressively, killing the host. We observed that 23 of 75 (31%) human tumor lines and two commonly used mouse tumor lines spontaneously produced GM-CSF. In mice, chronic GM-CSF production by tumors suppressed Ag-specific CD8+ T cell responses. Interestingly, an inhibitory population of adherent CD11b(Mac-1)/Gr-1 double-positive cells caused the observed impairment of CD8+ T cell function upon direct cell-to-cell contact. The inhibitory cells were positive for some markers associated with Ag presenting cells, like F4/80, but were negative for markers associated with fully mature DC like DEC205, B7.2, and MHC class II. We have previously reported that a similar or identical population of inhibitory “immature” APC was elicited after immunization with powerful recombinant immunogens. We show here that these inhibitory cells can be elicited by the administration of recombinant GM-CSF alone, and, furthermore, that they can be differentiated ex vivo into “mature” APC by the addition of IL-4 and GM-CSF. Thus, tumors may be able to escape from immune detection by producing “unopposed” GM-CSF, thereby disrupting the balance of cytokines needed for the maturation of fully functional DC. Further, CD11b/Gr-1 double-positive cells may function as “inhibitory” APC under the influence of GM-CSF alone. PMID:10229805

  20. Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites

    National Research Council Canada - National Science Library

    Wang, Ruobing; Richie, Thomas L; Baraceros, Maria F; Rahardjo, Nancy; Gay, Tanya; Banania, Jo-Glenna; Charoenvit, Yupin; Epstein, Judith E; Luke, Thomas; Freilich, Daniel A; Norman, Jon; Hoffman, Stephen L

    2004-01-01

    A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF...

  1. Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697).

    Science.gov (United States)

    Lawson, David H; Lee, Sandra; Zhao, Fengmin; Tarhini, Ahmad A; Margolin, Kim A; Ernstoff, Marc S; Atkins, Michael B; Cohen, Gary I; Whiteside, Theresa L; Butterfield, Lisa H; Kirkwood, John M

    2015-12-01

    We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma. Patients with completely resected stage IV or high-risk stage III melanoma were grouped by human leukocyte antigen (HLA) -A2 status. HLA-A2-positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2-negative patients, GM-CSF or placebo. Treatment lasted for 1 year or until recurrence. Efficacy analyses were conducted in the intent-to-treat population. A total of 815 patients were enrolled. There were no significant improvements in OS (stratified log-rank P = .528; hazard ratio, 0.94; 95% repeated CI, 0.77 to 1.15) or RFS (P = .131; hazard ratio, 0.88; 95% CI, 0.74 to 1.04) in the patients assigned to GM-CSF (n = 408) versus those assigned to placebo (n = 407). The median OS times with GM-CSF versus placebo treatments were 69.6 months (95% CI, 53.4 to 83.5 months) versus 59.3 months (95% CI, 44.4 to 77.3 months); the 5-year OS probability rates were 52.3% (95% CI, 47.3% to 57.1%) versus 49.4% (95% CI, 44.3% to 54.3%), respectively. The median RFS times with GM-CSF versus placebo were 11.4 months (95% CI, 9.4 to 14.8 months) versus 8.8 months (95% CI, 7.5 to 11.2 months); the 5-year RFS probability rates were 31.2% (95% CI, 26.7% to 35.9%) versus 27.0% (95% CI, 22.7% to 31.5%), respectively. Exploratory analyses showed a trend toward improved OS in GM-CSF-treated patients with resected visceral metastases. When survival in HLA-A2-positive patients who received PV versus placebo was compared, RFS and OS were not significantly different. Treatment-related grade 3 or greater adverse events were similar between GM-CSF and placebo groups. Neither adjuvant GM-CSF nor PV significantly improved RFS or OS in patients with high-risk resected melanoma. Exploratory analyses suggest

  2. Rapid transient expression of human granulocyte-macrophage colony-stimulating factor in two industrial cultivars of tobacco (Nicotiana tabacum L. by agroinfiltration

    Directory of Open Access Journals (Sweden)

    Lea Vojta

    2015-09-01

    Full Text Available We report the production of hGM-CSF cytokine in leaves of industrial tobacco cultivars DH-17 and DH-27 by using Agrobacterium-mediated transient expression. We prove the concept that very high biomass industrial tobacco plants are suitable platforms for rapid, low cost production of foreign proteins. Successful transient expression of the GM-CSF was achieved in less than three months, opening the possibility for future applications of this approach in rapid response production of various proteins of non-plant origin in industrial tobacco.

  3. Rapid transient expression of human granulocyte-macrophage colony-stimulating factor in two industrial cultivars of tobacco (Nicotiana tabacum L.) by agroinfiltration

    OpenAIRE

    Vojta, Lea; Ljuma-Skupnjak, Lana; Budimir, Ankica; Vukičević, Slobodan; Fulgosi, Hrvoje

    2015-01-01

    We report the production of hGM-CSF cytokine in leaves of industrial tobacco cultivars DH-17 and DH-27 by using Agrobacterium-mediated transient expression. We prove the concept that very high biomass industrial tobacco plants are suitable platforms for rapid, low cost production of foreign proteins. Successful transient expression of the GM-CSF was achieved in less than three months, opening the possibility for future applications of this approach in rapid response production of various prot...

  4. Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

    NARCIS (Netherlands)

    Withoff, S; Glazenburg, KL; van Veen, ML; Kraak, MMJ; Hospers, GAP; Storkel, S; de Vries, EGE; Wischut, J; Daemen, T

    2001-01-01

    This paper describes the production of recombinant Semliki Forest virus encoding murine or human granulocyte-macrophage colony-stimulating factor (GM-CSF) and the capacity of these vectors to transduce murine and human tumor cells ex vivo. High-titer stocks (up to 3 x 10(9) particles/ml) of

  5. Granulocyte-macrophage colony-stimulating factor does not increase the potency or efficacy of a foot-and-mouth disease virus subunit vaccine Fator estimulante de colônias de granu-lócitos e macrófagos (GM-CSF não aumenta a eficácia ou potência da vacina de subunidades da febre aftosa em suínos

    Directory of Open Access Journals (Sweden)

    Luizinho Caron

    2005-09-01

    Full Text Available Foot-and-mouth disease (FMD is one of the most feared diseases of livestock worldwide. Vaccination has been a very effective weapon in controlling the disease, however a number of concerns with the current vaccine including the inability of approved diagnostic tests to reliably distinguish vaccinated from infected animals and the need for high containment facilities for vaccine production, have limited its use during outbreaks in countries previously free of the disease. A number of FMD vaccine candidates have been tested and a replication-defective human adenovirus type 5 (Ad5 vector containing the FMDV capsid (P1-2A and 3C protease coding regions has been shown to completely protect pigs against challenge with the homologous virus (FMDV A12 and A24. An Ad5-P1-2A+3C vaccine for FMDV O1 Campos (Ad5-O1C, however, only induced a low FMDV-specific neutralizing antibody response in swine potency tests. Granulocyte-macrophage colony-stimulating factor (GM-CSF has been successfully used to stimulate the immune response in vaccine formulations against a number of diseases, including HIV, hepatitis C and B. To attempt to improve the FMDV-specific immune response induced by Ad5-O1C, we inoculated swine with Ad5-O1C and an Ad5 vector containing the gene for porcine GM-CSF (pGM-CSF. However, in the conditions used in this trial, pGM-CSF did not improve the immune response to Ad5-O1C and adversely affected the level of protection of swine challenged with homologous FMDV.A febre aftosa é uma das doenças mais temidas nos rebanhos em todo o mundo. A vacinação tem sido uma arma eficiente no controle da doença, no entanto há preocupações com as vacinas atualmente utilizadas incluindo a necessidade de instalações de alta segurança para a produção dessas vacinas e a falta de um teste de diagnóstico aprovado que faça distinção precisa entre animais vacinados dos infectados. Várias vacinas têm sido testadas contra a febre aftosa e uma dessas

  6. Effect of recombinant and purified hematopoietic growth factors on human megakaryocyte colony formation.

    Science.gov (United States)

    Bruno, E; Briddell, R; Hoffman, R

    1988-06-01

    The effect of a number of purified or recombinant hematopoietic growth factors, including recombinant erythropoietin (rEpo), thrombocytopoiesis stimulating factor (TSF), recombinant interleukin 1 alpha (rIL-1 alpha), recombinant granulocyte colony-stimulating factor (rG-CSF), macrophage colony-stimulating factor (CSF-1), recombinant interleukin 3 (rIL-3), and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on megakaryocyte (MK) colony formation by normal human marrow cells in a serum-depleted assay system was determined. Neither rEpo, TSF, CSF-1, rIL-1 alpha, nor rG-CSF alone augmented MK colony formation. Both rGM-CSF and rIL-3 at optimal doses increased MK colony formation eightfold and tenfold, respectively, above baseline values. Addition of increasing amounts of either rGM-CSF or rIL-3 led to progressively greater numbers of MK colonies formed until plateau levels were reached. Both rGM-CSF and rIL-3 also led to a dose-related increase in the number of cells per MK colony formed in culture. These molecules were equivalent stimulators of MK colony formation when their effects at optimal concentrations were compared. The effects of rGM-CSF and rIL-3 were additive at suboptimal concentrations of rIL-3 in that colony formation by a combination of the two growth factors approximated the sum of colony formation by each growth factor alone. These data suggest that rGM-CSF and rIL-3 alone and in combination are important regulators of in vitro megakaryocytopoiesis at the progenitor cell level.

  7. Effects of hematopoietic growth factors on in vitro colony formation by human megakaryocyte progenitor cells.

    Science.gov (United States)

    Lu, L; Bruno, E; Briddell, R A; Graham, C D; Brandt, J E; Hoffman, R

    1988-08-01

    In order to study the effects of recombinant and purified hematopoietic growth factors on megakaryocyte (MK) progenitor cells (CFU-MK), enriched populations of human CFU-MK were isolated utilizing fluorescence activated cell sorting after labelling of cells with monoclonal antibodies exhibiting specificity to the My10 (HPCA-1) antigen and the major histocompatibility (MHC) class II (HLA-DR) locus. The CFU-MK cloning efficiency (CE) was 1.1 +/- 0.5% for cells expressing both high densities of My10 and low densities of HLA-DR (My10 DR+). This procedure resulted in an 18 fold increase in CE over NALT- cells. The effects of natural or recombinant human hematopoietic growth factors including erythropoietin (Epo), thrombocytopoiesis stimulating factor (TSF), interleukin 1 alpha (IL-1 alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (CSF-1), and interleukin 3 (IL-3) on MK colony formation by My10 DR+ cells were determined utilizing a defined medium assay system. Neither Epo, TSF, CSF-1, IL-1 alpha nor G-CSF alone augmented MK colony formation above baseline (2.5 +/- 0.8 per 5 x 10(3) My10 DR+ cells plated). By contrast, the addition of GM-CSF and IL-3 each increased CFU-MK colony formation with maximal stimulation occurring following the addition of 200 units/ml of IL-3 and 100 units/ml of GM-CSF. At maximal concentration, IL-3 had a greater ability to promote megakaryocyte colony formation than GM-CSF.

  8. In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

    Science.gov (United States)

    Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

    2017-12-01

    The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10-9 to 10-7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony-stimulating factor

  9. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

    OpenAIRE

    Constantinescu, Cris S.; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P.; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E.; Sprenger, Till; Radue, Ernst W.

    2015-01-01

    Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infu...

  10. Effects of Granulocyte-Macrophage Colony-Stimulating Factor in Burn Patients

    Science.gov (United States)

    1991-01-01

    obtained from the bacterial fer- The values obtained when DBA was used as a probe corresponded to mentation of a strain of Escherichia coli bearing a...patients with leukopenia ing units was associated with a higher incidence of fatal secondary to aplastic anemia,’ acquired immunodeficiency septicemia

  11. Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells.

    OpenAIRE

    McNally, A. K.; Anderson, J. M.

    1995-01-01

    Interleukin-4 induced the formation of foreign body-type giant multinucleated cells from human monocyte-derived macrophages, an effect that was optimized with either granulocyte-macrophage colony-stimulating factor or interleukin-3, dependent on the concentration of interleukin-4, and specifically prevented by anti-interleukin-4. Very large foreign body giant cells and, predominantly, giant cell syncytia with randomly arranged nuclei and extensive cytoplasmic spreading (285 +/- 121 nuclei and...

  12. Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain.

    Science.gov (United States)

    Coughlan, Alice M; Harmon, Cathal; Whelan, Sarah; O'Brien, Eóin C; O'Reilly, Vincent P; Crotty, Paul; Kelly, Pamela; Ryan, Michelle; Hickey, Fionnuala B; O'Farrelly, Cliona; Little, Mark A

    2016-04-01

    Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rγc(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.

  13. Effect of recombinant and purified human haematopoietic growth factors on in vitro colony formation by enriched populations of human megakaryocyte progenitor cells.

    Science.gov (United States)

    Lu, L; Briddell, R A; Graham, C D; Brandt, J E; Bruno, E; Hoffman, R

    1988-10-01

    Nonadherent low density T-lymphocyte depleted (NALT-) marrow cells from normal donors were sorted on a Coulter Epics 753 Dye Laser System using Texas Red labelled My10 and phycoerythrin conjugated anti HLA-DR monoclonal antibodies in order to obtain enriched populations of colony forming unit-megakaryocyte (CFU-MK). The CFU-MK cloning efficiency (CE) was 1.1 +/- 0.5% for cells expressing both high densities of My10 and low densities of HLA-DR (My10 DR+). This procedure resulted in an 18-fold increase in CE over NALT- cells. The effect of purified or recombinant human haematopoietic growth factors including erythropoietin (Epo), thrombocytopoiesis stimulating factor (TSF), interleukin 1 alpha (IL-1 alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF or CSF-1) and interleukin MK colony formation by My10 DR+ cells was determined utilizing a serum depleted assay system. Neither Epo, TSF, CSF-1, IL-1 alpha nor G-CSF alone augmented MK colony formation above baseline (2.5 +/- 0.8/5 x 10(3) My10 DR+ cells plated). In contrast, the addition of GM-CSF and IL-3 each increased both CFU-MK colony formation and the size of colonies with maximal stimulation occurring following the addition of 200 units/ml of IL-3 and 25 units/ml of GM-CSF. At maximal concentration, IL-3 had a greater ability to promote megakaryocyte colony formation than GM-CSF. The stimulatory effects of GM-CSF and IL-3 were also additive in that the effects of a combination of the two factors approximated the sum of colony formation in the presence of each factor alone. The CFU-MK appears, therefore, to express HPCA-1 and HLA-DR antigens. These studies also indicate that GM-CSF and IL-3 are important in vitro regulators of megakaryocytopoiesis, and that these growth factors are not dependent on the presence of large numbers of macrophages or T cells for their activity since the My10 DR+ cells are largely

  14. Induction of Colony-Stimulating Factor Expression following Staphylococcus or Salmonella Interaction with Mouse or Human Osteoblasts

    Science.gov (United States)

    Bost, Kenneth L.; Bento, Jennifer L.; Ellington, John K.; Marriott, Ian; Hudson, Michael C.

    2000-01-01

    Staphylococcus aureus and Salmonella spp. are common causes of bone diseases; however, the immune response during such infections is not well understood. Colony-stimulating factors (CSF) have a profound influence on osteoclastogenesis, as well as the development of immune responses following infection. Therefore, we questioned whether interaction of osteoblasts with two very different bacterial pathogens could affect CSF expression by these cells. Cultured mouse and human osteoblasts were exposed to various numbers of S. aureus or Salmonella dublin bacteria, and a comprehensive analysis of granulocyte-macrophage (GM)-CSF, granulocyte (G)-CSF, macrophage (M)-CSF, and interleukin-3 (IL-3) mRNA expression and cytokine secretion was performed. Expression of M-CSF and IL-3 mRNAs by mouse osteoblasts was constitutive and did not increase significantly following bacterial exposure. In contrast, GM-CSF and G-CSF mRNA expression by mouse osteoblasts was dramatically upregulated following interaction with either viable S. aureus or Salmonella. This increased mRNA expression also translated into high levels of GM-CSF and G-CSF secretion by mouse and human osteoblasts following bacterial exposure. Viable S. aureus and Salmonella induced maximal levels of CSF mRNA expression and cytokine secretion compared to UV-killed bacteria. Furthermore, GM-CSF and G-CSF mRNA expression could be induced in unexposed osteoblasts separated by a permeable Transwell membrane from bacterially exposed osteoblasts. M-CSF secretion was increased in cultures of exposed human osteoblasts but not in exposed mouse osteoblast cultures. Together, these studies are the first to define CSF expression and suggest that, following bacterial exposure, osteoblasts may influence osteoclastogenesis, as well as the development of an immune response, via the production of these cytokines. PMID:10948128

  15. CXCR3 expression on CD34(+) hemopoietic progenitors induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Anting, L; Jacobi, H H

    2001-01-01

    CXCR3, known to have four ligands (IFN-gamma inducible protein 10 (gamma IP-10), monokine induced by IFN-gamma (Mig), I-TAC, and 6Ckine), is predominantly expressed on memory/activated T lymphocytes. We recently reported that GM-CSF induces CXCR3 expression on CD34(+) hemopoietic progenitors......, in which gamma IP-10 and Mig induce chemotaxis and adhesion. Here we further report that stimulation with GM-CSF causes phosphorylation of Syk protein kinase, but neither Casitas B-lineage lymphoma (Cbl) nor Cbl-b in CD34(+) hemopoietic progenitors can be blocked by anti-CD116 mAb. Specific Syk blocking...... generated by PNA antisense completely inhibits GM-CSF-induced CXCR3 expression in CD34(+) progenitors at both mRNA and protein as well as at functional levels (chemotaxis and adhesion). Cbl and Cbl-b blocking have no such effects. Thus, GM-CSF binds to its receptor CD116, and consequently activates Syk...

  16. The immunomodulatory effect of inhaled granulocyte-macrophage colony-stimulating factor in cystic fibrosis. A new treatment paradigm

    DEFF Research Database (Denmark)

    Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

    2012-01-01

    Patients with cystic fibrosis (CF) experience recurrent infections and develop chronically infected lungs, which initiates an altered immunological alveolar environment. End-stage pulmonary dysfunction is a result of a long sequence of complex events in CF, progressing to alveolar macrophage...

  17. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF) activity

    NARCIS (Netherlands)

    Isik, Gözde; van Montfort, Thijs; Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

    2013-01-01

    HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env

  18. Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow.

    OpenAIRE

    Brandt, J.; Srour, E F; van Besien, K.; Briddell, R A; Hoffman, R.

    1990-01-01

    Human marrow cells positive for the CD34 antigen but not expressing HLA-DR, CD15, or CD71 antigens were isolated. In a liquid culture system supplemented with 48-hourly additions of recombinant interleukins IL-1 alpha, IL-3, IL-6, or granulocyte/macrophage colony-stimulating factor (GM-CSF), these cells were capable of sustaining in vitro hematopoiesis for up to eight weeks. The establishment of an adherent cell layer was never observed. Cultures containing no exogenous cytokine produced clon...

  19. UCLA1 aptamer inhibition of human immunodeficiency virus type 1 subtype C primary isolates in macrophages and selection of resistance

    CSIR Research Space (South Africa)

    Mufhandu, Hazel T

    2016-09-01

    Full Text Available HIV-seronegative blood donors using the Ficoll-Hypaque method [10] and re-suspended in Lonza X-VIVO-10 culture media (Whitehead Scientific, S.A), supplemented with 10% fetal bovine serum (FBS, Gibco Invitrogen, South Africa). Cells were incubated...-suspended monocytes were cultured in Rosewell Park Memorial Institute (RPMI) medium supplemented with 10% FBS (10% RPMI growth media) and 5 ng/ml human granulocyte macrophage colony stimulating factor (hGM- 5 CSF) (Roche Diagnostics, Mannheim, Germany) for 5...

  20. Enhancement of Umbilical Cord Blood Cell Hematopoiesis by Maitake Beta-Glucan Is Mediated by Granulocyte Colony-Stimulating Factor Production▿

    Science.gov (United States)

    Lin, Hong; Cheung, Sandy W. Y.; Nesin, Mirjana; Cassileth, Barrie R.; Cunningham-Rundles, Susanna

    2007-01-01

    Maitake beta-glucan (MBG) is an extract from the fruit body of the Grifola frondosa mushroom that is being widely used to treat cancer in Asia. We have previously reported that MBG enhances mouse bone marrow cell (BMC) hematopoiesis in vitro and protects BMC from doxorubicin (DOX) toxicity. In the current study, we investigated the ability of MBG to enhance hematopoiesis and to reduce the toxic effects of DOX on fresh human umbilical cord blood (CB) cells. MBG treatment significantly enhanced the colony formation unit (CFU) response of granulocytes-macrophages (CFU-GM response) over the whole dose range of 12.5 to 100 μg/ml (P < 0.05). The addition of MBG to DOX-treated CB cells significantly protected granulocyte-macrophage colony formation from the toxicity of DOX, which otherwise produced strong hematopoietic repression. MBG also partially replaced recombinant human granulocyte colony-stimulating factor (rhG-CSF), as shown by a significant augmentation of the CFU-GM response in the absence of rhG-CSF. We found that MBG induces granulocyte colony-stimulating factor (G-CSF) production in CB CD33+ monocytes, as detected by intracellular cytokine flow cytometric assessment. In contrast, we found that adult peripheral blood monocytes did not produce a significant G-CSF response to MBG, whereas both adult and CB monocytes produced G-CSF in response to lipopolysaccharide. These studies provide the first evidence that MBG induces hematopoietic stem cell proliferation and differentiation of CFU-GM in umbilical CB cells and acts directly to induce G-CSF. PMID:17093103

  1. Characterization of the human burst-forming unit-megakaryocyte.

    Science.gov (United States)

    Briddell, R A; Brandt, J E; Straneva, J E; Srour, E F; Hoffman, R

    1989-07-01

    Two classes of human marrow megakaryocyte progenitor cells are described. Colony-forming unit-megakaryocyte (CFU-MK)-derived colonies appeared in vitro after 12-day incubation; burst-forming unit-megakaryocyte (BFU-MK)-derived colonies appeared after 21 days. CFU-MK-derived colonies were primarily unifocal and composed of 11.6 +/- 1.2 cells/colony; BFU-MK-derived colonies were composed of 2.3 +/- 0.4 foci and 108.6 +/- 4.4 cells/colony. CFU-MK and BFU-MK were separable by counterflow centrifugal elutriation. CFU-MK colony formation was diminished by exposure to 5-fluorouracil (5-FU); BFU-MK colony formation was unaffected. CFU-MK and BFU-MK were immunologically phenotyped. CFU-MK expressed the human progenitor cell antigen-1 (HPCA-1, CD34, clone My10) and a major histocompatibility class II locus, HLA-DR, and BFU-MK expressed only detectable amounts of CD34. BFU-MK colony formation was entirely dependent on addition of exogenous hematopoietic growth factors. Recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) possessed such colony-stimulating activity, whereas recombinant erythropoietin (Epo), G-CSF, IL-1 alpha, IL-4, and purified thrombocytopoiesis-stimulating factor did not. These studies indicate the existence of a human megakaryocyte progenitor cell, the BFU-MK, which has unique properties allowing it to be distinguished from the CFU-MK.

  2. Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells.

    Science.gov (United States)

    McNally, A K; Anderson, J M

    1995-11-01

    Interleukin-4 induced the formation of foreign body-type giant multinucleated cells from human monocyte-derived macrophages, an effect that was optimized with either granulocyte-macrophage colony-stimulating factor or interleukin-3, dependent on the concentration of interleukin-4, and specifically prevented by anti-interleukin-4. Very large foreign body giant cells and, predominantly, giant cell syncytia with randomly arranged nuclei and extensive cytoplasmic spreading (285 +/- 121 nuclei and 1.151 +/- 0.303 mm2 per syncytium) were consistently obtained. Under otherwise identical culture conditions, relatively much smaller Langhans-type giant cells with circularly arranged nuclei were induced with a previously described combination of interferon-gamma plus granulocyte-macrophage colony-stimulating factor or interleukin-3 (16 +/- 6 nuclei and 0.033 +/- 0.013 mm2 per giant cell); their formation was prevented by anti-interferon-gamma but not by anti-interleukin-4. Similar rates of macrophage fusion were obtained in both culture systems (72 +/- 5% and 74 +/- 6%, respectively), but these two morphological variants did not occur simultaneously or form from one another within the 10-day culture period. These findings demonstrate that interleukin-4 is a potent human macrophage fusion factor and that differential regulation of macrophage fusion by interleukin-4 and interferon-gamma may lead to morphological variants of multinucleated giant cells.

  3. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage.

    Science.gov (United States)

    Ushach, Irina; Zlotnik, Albert

    2016-09-01

    M-CSF and GM-CSF are 2 important cytokines that regulate macrophage numbers and function. Here, we review their known effects on cells of the macrophage-monocyte lineage. Important clues to their function come from their expression patterns. M-CSF exhibits a mostly homeostatic expression pattern, whereas GM-CSF is a product of cells activated during inflammatory or pathologic conditions. Accordingly, M-CSF regulates the numbers of various tissue macrophage and monocyte populations without altering their "activation" status. Conversely, GM-CSF induces activation of monocytes/macrophages and also mediates differentiation to other states that participate in immune responses [i.e., dendritic cells (DCs)]. Further insights into their function have come from analyses of mice deficient in either cytokine. M-CSF signals through its receptor (CSF-1R). Interestingly, mice deficient in CSF-1R expression exhibit a more significant phenotype than mice deficient in M-CSF. This observation was explained by the discovery of a novel cytokine (IL-34) that represents a second ligand of CSF-1R. Information about the function of these ligands/receptor system is still developing, but its complexity is intriguing and strongly suggests that more interesting biology remains to be elucidated. Based on our current knowledge, several therapeutic molecules targeting either the M-CSF or the GM-CSF pathways have been developed and are currently being tested in clinical trials targeting either autoimmune diseases or cancer. It is intriguing to consider how evolution has directed these pathways to develop; their complexity likely mirrors the multiple functions in which cells of the monocyte/macrophage system are involved. © Society for Leukocyte Biology.

  4. In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells.

    Science.gov (United States)

    Andrews, R G; Briddell, R A; Knitter, G H; Opie, T; Bronsden, M; Myerson, D; Appelbaum, F R; McNiece, I K

    1994-08-01

    Recombinant human stem cell factor (rhSCF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) are synergistic in vitro in stimulating the proliferation of hematopoietic progenitor cells and their precursors. We examined the in vivo synergy of rhSCF with rhG-CSF for stimulating hematopoiesis in vivo in baboons. Administration of low-dose (LD) rhSCF (25 micrograms/kg) alone did not stimulate changes in circulating WBCs. In comparison, administration of LD rhSCF in combination with rhG-CSF at 10 micrograms/kg or 100 micrograms/kg stimulated increases in circulating WBCs of multiple types up to twofold higher than was stimulated by administration of the same dose of rhG-CSF alone. When the dose of rhG-CSF is increased to 250 micrograms/kg, the administration of LD rhSCF does not further increase the circulating WBC counts. Administration of LD rhSCF in combination with rhG-CSF also stimulated increased circulation of hematopoietic progenitors. LD rhSCF alone stimulated less of an increase in circulating progenitors, per milliliter of blood, than did administration of rhG-CSF alone at 100 micrograms/kg. Baboons administered LD rhSCF together with rhG-CSF at 10, 100, or 250 micrograms/kg had 3.5- to 16-fold higher numbers per milliliter of blood of progenitors cells of multiple types, including colony-forming units granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming and burst-forming units-megakaryocyte (CFU-MK and BFU-MK) compared with animals given the same dose of rhG-CSF without rhSCF, regardless of the rhG-CSF dose. The increased circulation of progenitor cells stimulated by the combination of rhSCF plus rhG-CSF was not necessarily directly related to the increase in WBCs, as this effect on peripheral blood progenitors was observed even at an rhG-CSF dose of 250 micrograms/kg, where coadministration of LD rhSCF did not further increase WBC counts. Administration of very-low-dose rhSCF (2.5 micrograms/kg) with

  5. Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts

    NARCIS (Netherlands)

    Maier, Andrea B.; Maier, Ilko L.; Van Heemst, Diana; Westendorp, Rudi G.J.

    2008-01-01

    Replicative senescence of human fibroblasts in vitro has been used as a model for in vivo aging. The onset of replicative senescence varies between several months to years. A colony formation assay, critically dependent on growth speed, can be performed within weeks, and has been reported being an

  6. Influence of bronchial allergen challenge on histamine release by human basophils

    NARCIS (Netherlands)

    Lie, W. J.; van der Veen, M. J.; Knol, E. F.; Mul, F. P.; Jansen, H. M.; Roos, D.; van der Zee, J. S.

    2000-01-01

    Basophils can be primed by cytokines such as interleukin (IL) -3, IL-5 or granulocyte macrophage-colony stimulating factor (GM-CSF). It has been described that the concentrations of these cytokines are enhanced at sites of allergic inflammation as well as systemic in allergic asthma. To investigate

  7. GM-CSF promotes migration of human monocytes across the blood brain barrier

    NARCIS (Netherlands)

    Vogel, D.Y.S.; Kooij, G.; Heijnen, P.D.A.M.; Breur, M.; Peferoen, L.A.N.; van der Valk, P.; de Vries, H.E.; Amor, S.; Dijkstra, C.D.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte-macrophages colony-stimulating factor (GM-CSF) may play an

  8. Keratinocyte growth factor administration attenuates murine pulmonary mycobacterium tuberculosis infection through granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophage activation and phagolysosome fusion.

    Science.gov (United States)

    Pasula, Rajamouli; Azad, Abul K; Gardner, Jason C; Schlesinger, Larry S; McCormack, Francis X

    2015-03-13

    Augmentation of innate immune defenses is an appealing adjunctive strategy for treatment of pulmonary Mycobacterium tuberculosis infections, especially those caused by drug-resistant strains. The effect of intranasal administration of keratinocyte growth factor (KGF), an epithelial mitogen and differentiation factor, on M. tuberculosis infection in mice was tested in prophylaxis, treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis resulted in inoculum size-dependent weight loss and mortality. A single dose of KGF given 1 day prior to infection with 10(5) M. tuberculosis bacilli prevented weight loss and enhanced pulmonary mycobacterial clearance (compared with saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was delivered intranasally every third day for 15 days, but weight loss and bacillary growth resumed when KGF was withdrawn. For mice with a well established M. tuberculosis infection, KGF given every 3 days beginning on day 15 postinoculation was associated with reversal of weight loss and an increase in M. tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through mechanisms that included promotion of phagolysosome fusion and induction of nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide evidence that administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis infection. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Keratinocyte Growth Factor Administration Attenuates Murine Pulmonary Mycobacterium tuberculosis Infection through Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF)-dependent Macrophage Activation and Phagolysosome Fusion*

    Science.gov (United States)

    Pasula, Rajamouli; Azad, Abul K.; Gardner, Jason C.; Schlesinger, Larry S.; McCormack, Francis X.

    2015-01-01

    Augmentation of innate immune defenses is an appealing adjunctive strategy for treatment of pulmonary Mycobacterium tuberculosis infections, especially those caused by drug-resistant strains. The effect of intranasal administration of keratinocyte growth factor (KGF), an epithelial mitogen and differentiation factor, on M. tuberculosis infection in mice was tested in prophylaxis, treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis resulted in inoculum size-dependent weight loss and mortality. A single dose of KGF given 1 day prior to infection with 105 M. tuberculosis bacilli prevented weight loss and enhanced pulmonary mycobacterial clearance (compared with saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was delivered intranasally every third day for 15 days, but weight loss and bacillary growth resumed when KGF was withdrawn. For mice with a well established M. tuberculosis infection, KGF given every 3 days beginning on day 15 postinoculation was associated with reversal of weight loss and an increase in M. tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through mechanisms that included promotion of phagolysosome fusion and induction of nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide evidence that administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis infection. PMID:25605711

  10. A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8{sup +} T cell responses to rabies virus

    Energy Technology Data Exchange (ETDEWEB)

    Wanjalla, Celestine N.; Goldstein, Elizabeth F.; Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2012-05-10

    Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8{sup +} T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8{sup +} T cell response was significantly lower. This was partly likely due to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8{sup +} T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8{sup +} T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.

  11. Granulocyte-macrophage colony-stimulating factor (GM-CSF) targets myeloid leukocytes in the uterus during the post-mating inflammatory response in mice.

    Science.gov (United States)

    Robertson, S A; O'Connell, A C; Hudson, S N; Seamark, R F

    2000-03-01

    Factors in seminal plasma elicit a surge of GM-CSF expression in uterine epithelial cells after mating in mice. This study investigates the nature of the endometrial cell populations targeted by epithelial GM-CSF. In quantitative RT-PCR studies, expression of the alpha-subunit of the GM-CSF receptor (GM-CSF-R) parallelled GM-CSF expression, being maximal during the 48 h period after mating and declining thereafter. Expression of mRNA encoding beta-common chain (AIC2B) also increased after mating and remained high until the time of embryo implantation on day 4 of pregnancy. Cells expressing GM-CSF receptors were identified in sections of uterus on the day after mating using 125I-GM-CSF, and were located predominantly in the endometrial stroma subjacent to the luminal epithelium, co-localising with abundant populations of myeloid leukocytes. Cells expressing GM-CSF receptor were identified as macrophages, granulocytes and putative dendritic cells by flow cytometric analysis using lineage and receptor subunit specific antibodies. Recombinant GM-CSF injected into the uterine lumen of ovariectomised mice was found to elicit a dose-dependant accumulation of macrophages and granulocytes in the endometrium, in a pattern of distribution comparable to that seen in uteri after natural mating. Together, these data indicate a role for epithelial cell-derived GM-CSF in mediating the recruitment and potentially in modifying the behaviour of uterine leukocytes during the post-mating inflammatory response in mice.

  12. Relative contributions of human types 1 and 2 T-helper cell-derived eosinophilotrophic cytokines to development of eosinophilia

    NARCIS (Netherlands)

    Wierenga, E. A.; Backx, B.; Snoek, M.; Koenderman, L.; Kapsenberg, M. L.

    1993-01-01

    The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-derived interleukin (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were studied in the regulation of sequential events in the development of eosinophilia. Using eosinophils from normal donors and

  13. The helminth Trichuris suis suppresses TLR4-induced inflammatory responses in human macrophages

    DEFF Research Database (Denmark)

    Ottow, M. K.; Klaver, E. J.; van der Pouw Kraan, T. C. T. M.

    2014-01-01

    include innate immune cells that propagate inflammation in these diseases, like pro-inflammatory macrophages. We here investigated the effects of the helminth Trichuris suis soluble products (SPs) on the phenotype and function of human inflammatory (granulocyte-macrophage colony-stimulating factor (GM......-CSF)-differentiated) macrophages. Interestingly, we here show that T. suis SPs potently skew inflammatory macrophages into a more anti-inflammatory state in a Toll-like receptor 4 (TLR4)-dependent manner, and less effects are seen when stimulating macrophages with TLR2 or -3 ligands. Gene microarray analysis of GM......-CSF-differentiated macrophages further revealed that many TLR4-induced inflammatory mediators, including interleukin (IL)-12B, CCL1 and CXCL9, are downregulated by T. suis SPs. In particular, we observed a strong reduction in the expression and function of P2RX7, a purinergic receptor involved in macrophage inflammation...

  14. Water extraction on Mars for an expanding human colony.

    Science.gov (United States)

    Ralphs, M; Franz, B; Baker, T; Howe, S

    2015-11-01

    In-situ water extraction is necessary for an extended human presence on Mars. This study looks at the water requirements of an expanding human colony on Mars and the general systems needed to supply that water from the martian atmosphere and regolith. The proposed combination of systems in order to supply the necessary water includes a system similar to Honeybee Robotics' Mobile In-Situ Water Extractor (MISWE) that uses convection, a system similar to MISWE but that directs microwave energy down a borehole, a greenhouse or hothouse type system, and a system similar to the Mars Atmospheric Resource Recovery System (MARRS). It is demonstrated that a large water extraction system that can take advantage of large deposits of water ice at site specific locations is necessary to keep up with the demands of a growing colony. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  15. Immature dendritic cells selectively replicate macrophagetropic (M-tropic) human immunodeficiency virus type 1, while mature cells efficiently transmit both M- and T-tropic virus to T cells

    NARCIS (Netherlands)

    Granelli-Piperno, A.; Delgado, E.; Finkel, V.; Paxton, W.; Steinman, R. M.

    1998-01-01

    Dendritic cells (DCs) can develop from CD14+ peripheral blood monocytes cultured in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). By 6 days in culture, the cells have the characteristics of immature DCs and can be further induced to mature by inflammatory

  16. Long-term generation and expansion of human primitive hematopoietic progenitor cells in vitro.

    Science.gov (United States)

    Srour, E F; Brandt, J E; Briddell, R A; Grigsby, S; Leemhuis, T; Hoffman, R

    1993-02-01

    Although sustained production of committed human hematopoietic progenitor cells in long-term bone marrow cultures (LTBMC) is well documented, evidence for the generation and expansion of human primitive hematopoietic progenitor cells (PHPC) in such cultures is lacking. For that purpose, we attempted to determine if the human high proliferative potential colony-forming cell (HPP-CFC), a primitive hematopoietic marrow progenitor cell, is capable of generation and expansion in vitro. To that effect, stromal cell-free LTBMC were initiated with CD34+ HLA-DR-CD15- rhodamine 123dull bone marrow cells and were maintained with repeated addition of c-kit ligand and a synthetic interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein. By day 21 of LTBMC, a greater than twofold increase in the number of assayable HPP-CFC was detected. Furthermore, the production of HPP-CFC in LTBMC continued for up to 4 weeks, resulting in a 5.5-fold increase in HPP-CFC numbers. Weekly phenotypic analyses of cells harvested from LTBMC showed that the number of CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 x 10(4) by day 21. To examine further the nature of the in vitro HPP-CFC expansion, individual HPP-CFC colonies were serially cloned. Secondary cloning of individual, day 28 primary HPP-CFC indicated that 46% of these colonies formed an average of nine secondary colony-forming unit--granulocyte-macrophage (CFU-GM)--derived colonies, whereas 43% of primary HPP-CFC gave rise to between one and six secondary HPP-CFC colonies and 6 to 26 CFU-GM. These data show that CD34+ HLA-DR- CD15- rhodamine 123dull cells represent a fraction of human bone marrow highly enriched for HPP-CFC and that based on their regeneration and proliferative capacities, a hierarchy of HPP-CFC exists. Furthermore, these studies indicate that in the presence of appropriate cytokine stimulation, it is possible to expand the number of PHPC

  17. Colony forming cell (CFC) assay for human hematopoietic cells.

    Science.gov (United States)

    Sarma, Nayan J; Takeda, Akiko; Yaseen, Nabeel R

    2010-12-18

    Human hematopoietic stem/progenitor cells are usually obtained from bone marrow, cord blood, or peripheral blood and are used to study hematopoiesis and leukemogenesis. They have the capacity to differentiate into lymphoid and myeloid lineages. The colony forming cell (CFC) assay is used to study the proliferation and differentiation pattern of hematopoietic progenitors by their ability to form colonies in a semisolid medium. The number and the morphology of the colonies formed by a fixed number of input cells provide preliminary information about the ability of progenitors to differentiate and proliferate. Cells can be harvested from individual colonies or from the whole plate to further assess their numbers and differentiation states using flow cytometry and morphologic evaluation of Giemsa-stained slides. This assay is useful for assessing myeloid but not lymphoid differentiation. The term myeloid in this context is used in its wider sense to encompass granulocytic, monocytic, erythroid, and megakaryocytic lineages. We have used this assay to assess the effects of oncogenes on the differentiation of primary human CD34+ cells derived from peripheral blood. For this purpose cells are transduced with either control retroviral construct or a construct expressing the oncogene of interest, in this case NUP98-HOXA9. We employ a commonly used retroviral vector, MSCV-IRES-GFP, that expresses a bicistronic mRNA that produces the gene of interest and a GFP marker. Cells are pre-activated by growing in the presence of cytokines for two days prior to retroviral transduction. After another two days, GFP+ cells are isolated by fluorescence-activated cell sorting (FACS) and mixed with a methylcellulose-containing semisolid medium supplemented with cytokines and incubated till colonies appear on the surface, typically 14 days. The number and morphology of the colonies are documented. Cells are then removed from the plates, washed, counted, and subjected to flow cytometry and

  18. Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells.

    Science.gov (United States)

    Na, Yi Rang; Hong, Ji Hye; Lee, Min Yong; Jung, Jae Hun; Jung, Daun; Kim, Young Won; Son, Dain; Choi, Murim; Kim, Kwang Pyo; Seok, Seung Hyeok

    2015-10-01

    Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Further examination of the effects of recombinant cytokines on the proliferation of human megakaryocyte progenitor cells.

    Science.gov (United States)

    Bruno, E; Cooper, R J; Briddell, R A; Hoffman, R

    1991-06-01

    The effect of several recombinant cytokines, including interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1 alpha, on megakaryocyte (MK) colony formation by a normal human bone marrow subpopulation (CD34+ DR+), enriched for the MK colony-forming unit (CFU-MK), was studied using a serum-depleted, fibrin clot culture system. IL-3 and GM-CSF, but not IL-6 or IL-1 alpha, stimulated MK colony formation by CD34+ DR+ cells. However, the addition of IL-1 alpha to CD34+ DR+ cultures containing IL-6 resulted in the appearance of CFU-MK-derived colonies, suggesting that IL-6 requires the presence of IL-1 alpha to exhibit its MK colony-stimulating activity (MK-CSA). Addition of neutralizing antibodies to IL-3 and GM-CSF, but not to IL-6 and IL-1 alpha, specifically inhibited the MK-CSA of IL-3 and GM-CSF, respectively. The addition of either anti-IL-6, anti-IL-1 alpha, or anti-IL-3 antisera to cultures containing both IL-6 and IL-1 alpha totally abolished the MK-CSA of the IL-6/IL-1 alpha combination. However, neither anti-IL-3 nor anti-GM-CSF antisera could totally neutralize the additive effect of the combination of IL-3 and GM-CSF on MK colony formation, indicating that these two cytokines act by affecting distinct effector pathways. These results suggest that while IL-3 and GM-CSF can directly affect CFU-MK-derived colony formation, IL-1 alpha and IL-6 act in concert to promote de novo elaboration of IL-3 and thereby promote CFU-MK proliferative capacity.

  20. Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor.

    Science.gov (United States)

    Yan, X Q; Briddell, R; Hartley, C; Stoney, G; Samal, B; McNiece, I

    1994-08-01

    In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor-derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG-CSF. Furthermore, an increased number of cells with short-term and long-term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

  1. In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Berenyi, Erika [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Benko, Ilona [Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Vamosi, Gyoergy [Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Geresi, Krisztina [Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Tarkanyi, Ilona [3rd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Szegedi, Istvan [Department of Pediatrics, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Lukacs, Levente [Coordinating Department of Surgical Techniques, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Juhasz, Istvan [Department of Dermatology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Kiss, Csongor [Department of Pediatrics, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Fesues, Laszlo [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary); and others

    2011-07-08

    Highlights: {yields} s{sup 4}UMP a naturally occurring thiolated nucleotide, effectively inhibited the proliferation of JY cells in vitro and in vivo. {yields} s{sup 4}UMP decreased the cell number and colony forming activity of leukemia cells in SCID mice. {yields} The effect of s{sup 4}UMP was undetectable on the bone marrow of healthy mice. {yields} The biochemical changes of the treated cells suggested that s{sup 4}UMP induced apoptosis. -- Abstract: We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s{sup 4}UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s{sup 4}UMP on JY cells. Treatment of JY cells with s{sup 4}UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte-macrophage progenitor cells were 14-fold less sensitive to the nucleotide. In vivo effectiveness of s{sup 4}UMP was determined using xenograft SCID mouse model. s{sup 4}UMP decreased the cell number and colony forming activity of the total cell content of the femur of SCID mice transplanted with JY cells without affecting the bone marrow of healthy mice. These results suggest that s{sup 4}UMP alone or in combination with other clinically approved anti-leukemic remedies should be further explored as a potential novel therapeutic agent.

  2. Cytokine expression in human osteoblasts after antiseptic treatment: a comparative study between polyhexanide and chlorhexidine.

    Science.gov (United States)

    Röhner, Eric; Hoff, Paula; Gaber, Timo; Lang, Annemarie; Vörös, Pauline; Buttgereit, Frank; Perka, Carsten; Windisch, Christoph; Matziolis, Georg

    2015-02-01

    Chlorhexidine and polyhexanide are frequently used antiseptics in clinical practice and have a broad antimicrobial range. Both antiseptics are helpful medical agents for septic wound treatment with a high potential for defeating joint infections. Their effect on human osteoblasts has, so far, not been sufficiently evaluated. The aim of this study was to investigate the activating potential of polyhexanide and chlorhexidine on inflammatory cytokines/chemokines in human osteoblasts in vitro. Human osteoblasts were isolated and cultivated in vitro and then treated separately with 0.1% and 2% chlorhexidine and 0.04% polyhexanide as commonly applied concentrations in clinical practice. Detection of cell structure and cell morphology was performed by light microscopic inspection. Cytokine and chemokine secretion was determined by using a multiplex suspension array. Cell shrinking, defective cell membrane, and the loss of cell adhesion indicated cell damage of human osteoblasts after treatment with both antiseptics was evaluated by using light microscopy. Polyhexanide, but not chlorhexidine, caused human osteoblasts to secrete various interleukins (1β, 6, and 7), interferon γ, tumor necrosis factor α, vascular endothelial growth factor, eotaxin, fibroblast growth factor basic, and granulocyte macrophage colony-stimulating factor as quantified by multiplex suspension array. Both antiseptics induced morphological cell damage at an optimum exposure between 1 and 10 min. But only polyhexanide mediated a pronounced secretion of inflammatory cytokines and chemokines in human osteoblasts. Therefore, we recommend a preferred usage of chlorhexidine in septic surgery to avoid the induction of an inflammatory reaction.

  3. Cytokine regulation of the human burst-forming unit-megakaryocyte.

    Science.gov (United States)

    Briddell, R A; Hoffman, R

    1990-08-01

    The human burst-forming unit-megakaryocyte (BFU-MK) is a primitive megakaryocytic progenitor cell. A marrow cell population enriched for BFU-MK (CD34+ DR-) was obtained by monoclonal antibody labeling and fluorescence-activated cell sorting. CD34+DR- cells were assayed in a serum-depleted, fibrin clot culture system. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant interleukin-3 (rIL-3), and megakaryocyte colony-stimulating factor (MK-CSF), partially purified from human plasma, were each individually capable of promoting BFU-MK-derived colony formation. Recombinant erythropoietin, rG-CSF, rIL-4, rIL-6, and thrombocytopiesis stimulating factor, partially purified from human embryonic kidney cell conditioned media, had no stimulatory effect on BFU-MK-derived colony formation when added alone or in various combinations with either GM-CSF, IL-3, or MK-CSF, GM-CSF and IL-3, GM-CSF and MK-CSF, but not IL-3 and MK-CSF had additive actions in promoting BFU-MK-derived colony formation, rIL-1 alpha had no influence alone on BFU-MK cloning efficiency, but had a dose-dependent, synergistic effect with IL-3, but not with GM-CSF or MK-CSF. The synergistic relationship between IL-1 alpha and IL-3 was abrogated by addition of an IL-1 alpha neutralizing antibody but not by a GM-CSF neutralizing antiserum, suggesting that IL-1 alpha acts directly on the BFU-MK and not by stimulating marrow auxiliary cells to secondarily release additional cytokines. Information presented here indicates that the regulatory influence, acting on the different stages of megakaryocyte development, are stage-specific and accomplished by multiple cytokines.

  4. Effect of c-kit ligand on in vitro human megakaryocytopoiesis.

    Science.gov (United States)

    Briddell, R A; Bruno, E; Cooper, R J; Brandt, J E; Hoffman, R

    1991-12-01

    An evaluation of the effects of a recombinant, soluble form of the c-kit ligand alone and in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) on the regulation of human megakaryocytopoiesis was performed using a serum-depleted clonal assay system and a long-term bone marrow culture system. The effects of the c-kit ligand on the primitive megakaryocyte (MK) progenitor cell, the burst-forming unit-megakaryocyte (BFU-MK), and the more differentiated colony-forming unit-megakaryocyte (CFU-MK) were determined. The c-kit ligand alone had no megakaryocyte colony-stimulating activity (MK-CSA) but was capable of augmenting the MK-CSA of both GM-CSF and IL-3. The range of synergistic interactions of c-kit ligand varied with the class of MK progenitor cell assayed. In the case of the BFU-MK, the c-kit ligand synergistically augmented the numbers of colonies formed in the presence of IL-3, but not GM-CSF, but increased the size of BFU-MK-derived colonies cloned in the presence of both of these cytokines. However, at the level of the CFU-MK, c-kit ligand synergized with both GM-CSF and IL-3 by increasing both colony numbers and size. Although the c-kit ligand alone exhibited limited potential in sustaining long-term megakaryocytopoiesis in vitro, it synergistically augmented the ability of IL-3, but not GM-CSF, to promote long-term megakaryocytopoiesis. These data indicate that multiple cytokines are necessary to optimally stimulate the proliferation of both classes of MK progenitor cells and that the c-kit ligand plays a significant role in this process by amplifying the MK-CSA of both GM-CSF and IL-3.

  5. Humans in Biogeophysical Models: Colonial Period Human-Environment Interactions in the Northeastern United States

    Science.gov (United States)

    Parolari, A.; Greco, F.; Green, M.; Lally, M.; Hermans, C.

    2008-12-01

    Earth system models increasingly require representation of human activities and the important role they play in the environment. At the most fundamental level, human decisions are driven by the need to acquire basic resources - nutrients, energy, water, and space - each derived from the biogeophysical setting. Modern theories in Ecological Economics place these basic resources at the base of a consumption hierarchy (from subsistence to luxury resources) on which societies and economies are built. Human decisions at all levels of this hierarchy are driven by dynamic environmental, social, and economic factors. Therefore, models merging socio-economic and biogeophysical dynamics are required to predict the evolving relationship between humans and the hydrologic cycle. To provide an example, our study focuses on changes to the hydrologic cycle during the United States colonial period (1600 to 1800). Both direct, intentional, human water use (e.g. water supply, irrigation, or hydropower) and indirect, unintentional effects resulting from the use of other resources (e.g. deforestation or beaver trapping) are considered. We argue that water was not the limiting resource to either the Native or Colonist population growth. However, food and tobacco production and harvesting of beaver pelts led to indirect interventions and consequent changes in the hydrologic cycle. The analysis presented here suggests the importance of incorporating human decision- making dynamics with existing geophysical models to fully understand trajectories of human-environment interactions. Predictive tools of this type are critical to characterizing the long-term signature of humans on the landscape and hydrologic cycle.

  6. Pattern-recognition receptors in human eosinophils.

    Science.gov (United States)

    Kvarnhammar, Anne Månsson; Cardell, Lars Olaf

    2012-05-01

    The pattern-recognition receptor (PRR) family includes Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and the receptor for advanced glycation end products (RAGE). They recognize various microbial signatures or host-derived danger signals and trigger an immune response. Eosinophils are multifunctional leucocytes involved in the pathogenesis of several inflammatory processes, including parasitic helminth infection, allergic diseases, tissue injury and tumour immunity. Human eosinophils express several PRRs, including TLR1-5, TLR7, TLR9, NOD1, NOD2, Dectin-1 and RAGE. Receptor stimulation induces survival, oxidative burst, activation of the adhesion system and release of cytokines (interleukin-1β, interleukin-6, tumour necrosis factor-α and granulocyte-macrophage colony-stimulating factor), chemokines (interleukin-8 and growth-related oncogene-α) and cytotoxic granule proteins (eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase and major basic protein). It is also evident that eosinophils play an immunomodulatory role by interacting with surrounding cells. The presence of a broad range of PRRs in eosinophils indicates that they are not only involved in defence against parasitic helminths, but also against bacteria, viruses and fungi. From a clinical perspective, eosinophilic PRRs seem to be involved in both allergic and malignant diseases by causing exacerbations and affecting tumour growth, respectively. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  7. GM-CSF promotes migration of human monocytes across the blood brain barrier.

    Science.gov (United States)

    Vogel, Daphne Y S; Kooij, Gijs; Heijnen, Priscilla D A M; Breur, Marjolein; Peferoen, Laura A N; van der Valk, Paul; de Vries, Helga E; Amor, Sandra; Dijkstra, Christine D

    2015-06-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte-macrophages colony-stimulating factor (GM-CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood-brain barrier. This study describes the effect of GM-CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM-CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM-CSF enhances monocyte migration across human blood-brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM-CSF is highly expressed by microglia and macrophages in MS lesions. The GM-CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM-CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM-CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow.

    Science.gov (United States)

    Brandt, J; Srour, E F; van Besien, K; Briddell, R A; Hoffman, R

    1990-09-01

    Human marrow cells positive for the CD34 antigen but not expressing HLA-DR, CD15, or CD71 antigens were isolated. In a liquid culture system supplemented with 48-hourly additions of recombinant interleukins IL-1 alpha, IL-3, IL-6, or granulocyte/macrophage colony-stimulating factor (GM-CSF), these cells were capable of sustaining in vitro hematopoiesis for up to eight weeks. The establishment of an adherent cell layer was never observed. Cultures containing no exogenous cytokine produced clonogenic cells for only 1 wk. IL-1 alpha and IL-6 were alone able to support hematopoiesis for 2 or 3 wk. Cells maintained with GM-CSF proliferated and contained assayable colony-forming cells for 3 or 4 wk, while maximal cellular expansion and generation of assayable progenitor cells occurred in the presence of IL-3 for 4-5 wk. When IL-3 was combined with IL-1 alpha or IL-6, hematopoiesis was sustained for 8 wks. Basophil numbers were markedly increased in the presence of IL-3. These studies indicate that marrow subpopulations can sustain hematopoiesis in vitro in the presence of repeated additions of cytokines. We conclude that a major function of marrow adherent cells in long-term cultures is that of providing cytokines which promote the proliferation and differentiation of primitive hematopoietic cells.

  9. Multi-nucleated giant cell formation from human cord blood monocytes in vitro, in comparison with adult peripheral blood monocytes.

    Science.gov (United States)

    Kondo, Y; Yasui, K; Yashiro, M; Tsuge, M; Kotani, N; Morishima, T

    2009-10-01

    Multi-nucleated giant cells (MGCs; Langhans-type cell), formed from macrophage fusion, are recognized as a hallmark histological feature in chronic inflammation. However, their precise pathological role is still poorly understood, especially for microorganism pathogens in the neonatal immune system, which are capable of surviving intracellularly in phagocytes. To conduct a partial evaluation of the monocyte function of neonates, we investigated the ability of human cord blood monocytes to form MGCs in vitro by stimulating various cytokines and comparing them with adult peripheral blood monocytes. Monocytes from cord blood and adult peripheral blood were isolated and cultured for 14 days with cytokines known to induce MGC in vitro. The fusion index in experiments with a combination of interleukin (IL)-4 and macrophage colony-stimulating factor (M-CSF) and a combination of IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly lower in cord blood than in adult blood monocytes (P = 0.0018 and P = 0.0141, respectively). The number of nuclei per MGC was significantly lower in cord blood than in adult blood monocytes in experiments with IL-4 alone, the combination of IL-4 and M-CSF, and the combination of IL-4 and GM-CSF (P < 0.0001). These results suggest the possibility that the susceptibility of newborns to mycobacterium infection is due partly to impaired MGC formation.

  10. Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis.

    OpenAIRE

    Rhoades, K L; Hetherington, C.J.; Rowley, J. D.; Hiebert, S W; Nucifora, G; Tenen, D G; Zhang, D E

    1996-01-01

    AML1 is involved in the (8;21) translocation, associated with acute myelogenous leukemia (AML)-type M2, which results in the production of the AML1-ETO fusion protein: the amino-terminal 177 amino acids of AML1 and the carboxyl-terminal 575 amino acids of ETO. The mechanism by which AML1-ETO accomplishes leukemic transformation is unknown; however, AML1-ETO interferes with AML1 transactivation of such AML1 targets as the T-cell receptor beta enhancer and the granulocyte-macrophage colony-stim...

  11. Innate Response Activator (IRA B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Directory of Open Access Journals (Sweden)

    Nico Chiappini

    Full Text Available Innate response activator (IRA B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  12. Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Science.gov (United States)

    Chiappini, Nico; Cantisani, Rocco; Pancotto, Laura; Ruggiero, Paolo; Rosa, Domenico; Manetti, Andrea; Romano, Antonio; Montagnani, Francesca; Bertholet, Sylvie; Castellino, Flora; Del Giudice, Giuseppe

    2015-01-01

    Innate response activator (IRA) B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA) B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  13. Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer

    NARCIS (Netherlands)

    de Gast, G. C.; Vyth-Dreese, F. A.; Nooijen, W.; van den Bogaard, C. J. C.; Sein, J.; Holtkamp, M. M. J.; Linthorst, G. A. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

    2002-01-01

    PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune

  14. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

    OpenAIRE

    Harrington KJ; Andtbacka RHI; Collichio F; Downey G; Chen L; Szabo Z; Kaufman HL

    2016-01-01

    Kevin J Harrington,1 Robert HI Andtbacka,2 Frances Collichio,3 Gerald Downey,4 Lisa Chen,5 Zsolt Szabo,6 Howard L Kaufman7 1The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre, London, UK; 2Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; 3Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Amgen Ltd, Cambridge, UK; 5Amgen Inc, Thousand Oaks, CA, USA; 6Amgen GmbH, Zug, Swit...

  15. Proangiogenic cell colonies grown in vitro from human peripheral blood mononuclear cells.

    Science.gov (United States)

    Mavromatis, Kreton; Sutcliffe, Diane J; Joseph, Giji; Alexander, R Wayne; Waller, Edmund K; Quyyumi, Arshed A; Taylor, W Robert

    2012-10-01

    Although multiple culture assays have been designed to identify endothelial progenitor cells (EPCs), the phenotype of cells grown in culture often remains undefined. We sought to define and characterize the proangiogenic cell population within human peripheral blood mononuclear cells. Mononuclear cells were isolated from peripheral blood and grown under angiogenic conditions for 7 days. Formed colonies (CFU-As) were identified and analyzed for proliferation, mRNA and surface antigen expression, tube-forming ability, and chromosomal content. Colonies were composed of a heterogeneous group of cells expressing the leukocyte antigens CD45, CD14, and CD3, as well as the endothelial proteins vascular endothelial (VE) cadherin, von Willebrand's factor (vWF), CD31, and endothelial nitric oxide synthase (eNOS). Colony cells expressed increased levels of proangiogenic growth factors, and they formed tubes in Matrigel. In comparison with colonies from the CFU-Hill assay, our assay resulted in a greater number of colonies (19 ± 9 vs. 13 ± 7; p < 0.0001) with a substantial number of cells expressing an endothelial phenotype (20.2% ± 7.4% vs. 2.2% ± 1.2% expressing eNOS, p = 0.0006). Chromosomal analysis indicated the colony cells were bone marrow derived. We, therefore, describe a colony-forming unit assay that measures bone marrow-derived circulating mononuclear cells with the capacity to proliferate and mature into proangiogenic leukocytic and endothelial-like cells. This assay, therefore, reflects circulating, bone marrow-derived proangiogenic activity.

  16. Gclust Server: 106731 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) ; no annotation 1 1.00e-99...colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) ; no annotation Number

  17. A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion

    Directory of Open Access Journals (Sweden)

    Elisa Närvä

    2017-07-01

    Full Text Available Cell-type-specific functions and identity are tightly regulated by interactions between the cell cytoskeleton and the extracellular matrix (ECM. Human pluripotent stem cells (hPSCs have ultimate differentiation capacity and exceptionally low-strength ECM contact, yet the organization and function of adhesion sites and associated actin cytoskeleton remain poorly defined. We imaged hPSCs at the cell-ECM interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers. The actin fence encircling the colony was found to exert extensive Rho-ROCK-myosin-dependent mechanical stress to enforce colony morphology, compaction, and pluripotency and to define mitotic spindle orientation. Remarkably, differentiation altered adhesion organization and signaling characterized by a switch from ventral to dorsal stress fibers, reduced mechanical stress, and increased integrin activity and cell-ECM adhesion strength. Thus, pluripotency appears to be linked to unique colony organization and adhesion structure.

  18. [Endomorphine-1 inhibits maturation and functions of human peripheral blood-derived dendritic cells].

    Science.gov (United States)

    Yang, Lijuan; Wang, Ya; Pan, Zhiyu; Chen, Yong; Xia, Hui; Li, Zhenghong

    2016-04-01

    To investigate the effects of endomorphine-1 (EM-1) on the functional features of lipopolysaccharide (LPS)-stimulated peripheral blood-derived dendritic cells (PBDCs), including PBDC phenotypes, cytokine profile and its capability of promoting T cell proliferation. PBDCs were isolated from peripheral blood and differentiated in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4). Then the cells were further activated by LPS or EM-1. Several surface markers were detected by flow cytometry including CD80, CD86, CD83, HLA-DR and CCR7. ELISA was used to detect cytokine levels of IL-10, IL-12, IFN-γ in the supernatants of the cultured PBDCs. Using co-culture of T lymphocytes and PBDCs stimulated by EM-1, the proliferation of T cells induced by PBDCs was determined by 5, 6-carboxyfluorescein succinimidyl ester (CFSE) staining. EM-1 down-regulated the expressions of CD80, CD86, CD83, HLA-DR and CCR7 on the activated PBDCs. Moreover, EM-1 decreased the secretion of IL-12 and IL-10 in these PBDCs. In co-culture of T lymphocytes and EM-1-treated PBDCs, T cell proliferation was impaired, and less IL-12 and IFN-γ were produced in the culture supernatant. EM-1 could inhibit the maturation and immune functions of PBDCs.

  19. Effects of thrombocytopoiesis-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes.

    Science.gov (United States)

    Straneva, J E; Briddell, R A; McDonald, T P; Yang, H H; Hoffman, R

    1989-12-01

    Aplastic anemia serum (AAS) contains humoral factors that alter both proliferation and maturation of human megakaryocytes (MK). The ability of AAS to augment MK colony formation (colony-forming unit, CFU-MK) was neutralized by an antiserum against MK colony-stimulating factor (MK-CSF), a glycoprotein isolated from AAS. The adsorbed AAS still retained the ability to accelerate cytoplasmic maturation of recognizable MK. Similar experiments were done with thrombocytopoiesis-stimulating factor (TSF) and an anti-TSF antiserum to further define the activity in AAS responsible for accelerating cytoplasmic maturation. Bone marrow fractions enriched for recognizable human MK, but devoid of CFU-MK, were obtained by centrifugal elutriation and placed in short-term liquid cultures. MK progressed through identifiable maturation stages (1-4) more quickly in the presence of either TSF or AAS. TSF slightly enhanced the cloning efficiencies of CFU-MK, but did not alter the number of MK in individual colonies derived from non-adherent, low-density, T-cell-depleted bone marrow. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and crude AAS substantially augmented both MK colony formation and cells per colony. TSF also doubled the percent 35S incorporation into platelets of immunothrombocythemic mice, but stimulation was completely abolished by anti-TSF. Anti-TSF antiserum was then used to analyze the promotion of MK colony formation by cytokines. Cloning efficiencies of CFU-MK were reduced to baseline values when TSF was pretreated with anti-TSF; however, the MK colony-stimulating activity (MK-CSA) of GM-CSF, IL-3, or AAS was not altered by adsorption with anti-TSF. In contrast, the cytoplasmic maturation of recognizable MK was slower, and fewer mature stage-4 cells were present at days 1-3 in AAS adsorbed with anti-TSF than MK cultured in AAS treated with normal rabbit serum or untreated AAS. Therefore, TSF appears to be a major factor in

  20. B-cell maturation antigen (BCMA) activation exerts specific proinflammatory effects in normal human keratinocytes and is preferentially expressed in inflammatory skin pathologies.

    Science.gov (United States)

    Alexaki, Vassilia-Ismini; Pelekanou, Vassiliki; Notas, George; Venihaki, Maria; Kampa, Marilena; Dessirier, Valérie; Sabour-Alaoui, Sanaa; Stathopoulos, Efstathios N; Tsapis, Andreas; Castanas, Elias

    2012-02-01

    TNFα is known to be expressed in human skin, regulating immune-related responses. Here we report that human normal skin keratinocytes express the members of the TNF superfamily members A proliferation-inducing ligand (APRIL; TNFSF13), B cell-activating factor (BAFF; TNFSF13B), and their receptors, B cell maturation antigen (BCMA; TNFRSF17) and transmembrane activator, calcium-modulator, and cyclophilin ligand interactor (TACI; TNFRSF13B), in a distinct spatial pattern. Our data show a differential expression of these molecules within epidermal layers and skin appendages, whereas the BAFF-specific receptor BAFFR (TNFRSF13C) is absent. Importantly, APRIL and BCMA but not BAFF or TACI are up-regulated in inflammatory skin lesions of psoriasis and squamous cell carcinomas. To explore the functional significance of this system in the skin, we assayed these receptors and ligands in cultured primary keratinocytes and HaCaT cells. We show that both cell types express BAFF, APRIL, BCMA, and TACI. Furthermore, APRIL and/or BAFF trigger nuclear factor-κB activation and IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) expression through functional BCMA receptors, an activation inhibited by anti-BCMA short hairpin RNA. However, BAFF and/or APRIL do not induce IL-8 or TNFα production. Our data advance BCMA as an inflammation-related TNFSFR member in keratinocytes, of potential importance in the management of inflammatory skin conditions.

  1. TGF-β Affects the Differentiation of Human GM-CSF+ CD4+ T Cells in an Activation- and Sodium-Dependent Manner.

    Science.gov (United States)

    Éliás, Szabolcs; Schmidt, Angelika; Kannan, Venkateshan; Andersson, John; Tegnér, Jesper

    2016-01-01

    The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the pathogenesis of chronic inflammatory diseases such as multiple sclerosis. However, the environmental cues promoting differentiation of GM-CSF producing T cells are unclear. Herein, we performed a broad experimental screening of cytokines and data-driven analysis assessing their ability to induce human GM-CSF+ CD4+ T cells and their subpopulations. TGF-β was discovered to induce GM-CSF production independently of proliferation and IL-2 signaling including STAT5. In contrast, IL-6 and IL-23 decreased GM-CSF production. On the population level, GM-CSF induction was highly correlated with expression of FOXP3 across cytokine stimulations but not with that of IL-17. However, on single-cell level GM-CSF and IFN-γ expression were most correlated, independently of the cytokine environment. Importantly, under low sodium conditions in the medium or upon stimulation with plate-bound instead of bead-bound anti-CD3 and anti-CD28 antibodies, the effects of TGF-β on GM-CSF, but not on FOXP3, were reversed. Our analysis indicates a novel role for TGF-β in generating GM-CSF+ subsets of human CD4+ T cells. These results are important for understanding of autoimmune disease and therapeutic considerations.

  2. Parametric analysis of colony morphology of non-labelled live human pluripotent stem cells for cell quality control.

    Science.gov (United States)

    Kato, Ryuji; Matsumoto, Megumi; Sasaki, Hiroto; Joto, Risako; Okada, Mai; Ikeda, Yurika; Kanie, Kei; Suga, Mika; Kinehara, Masaki; Yanagihara, Kana; Liu, Yujung; Uchio-Yamada, Kozue; Fukuda, Takayuki; Kii, Hiroaki; Uozumi, Takayuki; Honda, Hiroyuki; Kiyota, Yasujiro; Furue, Miho K

    2016-09-26

    Given the difficulties inherent in maintaining human pluripotent stem cells (hPSCs) in a healthy state, hPSCs should be routinely characterized using several established standard criteria during expansion for research or therapeutic purposes. hPSC colony morphology is typically considered an important criterion, but it is not evaluated quantitatively. Thus, we designed an unbiased method to evaluate hPSC colony morphology. This method involves a combination of automated non-labelled live-cell imaging and the implementation of morphological colony analysis algorithms with multiple parameters. To validate the utility of the quantitative evaluation method, a parent cell line exhibiting typical embryonic stem cell (ESC)-like morphology and an aberrant hPSC subclone demonstrating unusual colony morphology were used as models. According to statistical colony classification based on morphological parameters, colonies containing readily discernible areas of differentiation constituted a major classification cluster and were distinguishable from typical ESC-like colonies; similar results were obtained via classification based on global gene expression profiles. Thus, the morphological features of hPSC colonies are closely associated with cellular characteristics. Our quantitative evaluation method provides a biological definition of 'hPSC colony morphology', permits the non-invasive monitoring of hPSC conditions and is particularly useful for detecting variations in hPSC heterogeneity.

  3. A novel and simple method for generation of human dendritic cells from unfractionated peripheral blood mononuclear cells within 2 days: its application for induction of HIV-1-reactive CD4(+) T cells in the hu-PBL SCID mice.

    Science.gov (United States)

    Kodama, Akira; Tanaka, Reiko; Saito, Mineki; Ansari, Aftab A; Tanaka, Yuetsu

    2013-01-01

    Because dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. Generally, monocyte-derived DCs (MDDCs) were generated from purified monocytes by multiple steps of time-consuming physical manipulations for an extended period cultivation. In this study, we developed a novel, simple and rapid method for the generation of type-1 helper T cell (Th1)-stimulating human DCs directly from bulk peripheral blood mononuclear cells (PBMCs). PBMCs were cultivated in the presence of 20 ng/ml of granulocyte-macrophage colony-stimulating factor, 20 ng/ml of interleukin-4 (IL-4) and 1,000 U/ml of interferon-β for 24 h followed by 24 h maturation with a cytokine cocktail containing 10 ng/ml of tumor necrosis factor-α (TNF-α), 10 ng/ml of IL-1β and 1 μg/ml of prostaglandin E2. The phenotype and biological activity of these new DCs for induction of allogeneic T cell proliferation and cytokine production were comparable to those of the MDDCs. Importantly, these new DCs pulsed with inactivated HIV-1 could generated HIV-1-reactive CD4(+) T cell responses in humanized mice reconstituted with autologous PBMCs from HIV-1-negative donors. This simple and quick method for generation of functional DCs will be useful for future studies on DC-mediated immunotherapies.

  4. Error-Correcting Output Codes in Classification of Human Induced Pluripotent Stem Cell Colony Images

    Directory of Open Access Journals (Sweden)

    Henry Joutsijoki

    2016-01-01

    Full Text Available The purpose of this paper is to examine how well the human induced pluripotent stem cell (hiPSC colony images can be classified using error-correcting output codes (ECOC. Our image dataset includes hiPSC colony images from three classes (bad, semigood, and good which makes our classification task a multiclass problem. ECOC is a general framework to model multiclass classification problems. We focus on four different coding designs of ECOC and apply to each one of them k-Nearest Neighbor (k-NN searching, naïve Bayes, classification tree, and discriminant analysis variants classifiers. We use Scaled Invariant Feature Transformation (SIFT based features in classification. The best accuracy (62.4% is obtained with ternary complete ECOC coding design and k-NN classifier (standardized Euclidean distance measure and inverse weighting. The best result is comparable with our earlier research. The quality identification of hiPSC colony images is an essential problem to be solved before hiPSCs can be used in practice in large-scale. ECOC methods examined are promising techniques for solving this challenging problem.

  5. Error-Correcting Output Codes in Classification of Human Induced Pluripotent Stem Cell Colony Images.

    Science.gov (United States)

    Joutsijoki, Henry; Haponen, Markus; Rasku, Jyrki; Aalto-Setälä, Katriina; Juhola, Martti

    2016-01-01

    The purpose of this paper is to examine how well the human induced pluripotent stem cell (hiPSC) colony images can be classified using error-correcting output codes (ECOC). Our image dataset includes hiPSC colony images from three classes (bad, semigood, and good) which makes our classification task a multiclass problem. ECOC is a general framework to model multiclass classification problems. We focus on four different coding designs of ECOC and apply to each one of them k-Nearest Neighbor (k-NN) searching, naïve Bayes, classification tree, and discriminant analysis variants classifiers. We use Scaled Invariant Feature Transformation (SIFT) based features in classification. The best accuracy (62.4%) is obtained with ternary complete ECOC coding design and k-NN classifier (standardized Euclidean distance measure and inverse weighting). The best result is comparable with our earlier research. The quality identification of hiPSC colony images is an essential problem to be solved before hiPSCs can be used in practice in large-scale. ECOC methods examined are promising techniques for solving this challenging problem.

  6. Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images

    OpenAIRE

    Henry Joutsijoki; Markus Haponen; Jyrki Rasku; Katriina Aalto-Setälä; Martti Juhola

    2016-01-01

    The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient’s cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can b...

  7. A framework for analysis of abortive colony size distributions using a model of branching processes in irradiated normal human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tetsuya Sakashita

    Full Text Available BACKGROUND: Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation, but an abortive colony that fails to continue to grow remains poorly characterized. It was recently reported that the fraction of abortive colonies increases with increasing dose. Thus, we set out to investigate the production kinetics of abortive colonies using a model of branching processes. METHODOLOGY/PRINCIPAL FINDINGS: We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-linear or log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD over several generations following irradiation. To verify the estimated probability of RCD, abortive colony size distribution (≤ 15 cells and the surviving fraction were simulated by the Monte Carlo computational approach for colony expansion. Parameters estimated from the log-log fit demonstrated the good performance in both simulations than those from the log-linear fit. Radiation-induced RCD, i.e. excess probability, lasted over 16 generations and mainly consisted of two components in the early (<3 generations and late phases. Intriguingly, the survival curve was sensitive to the excess probability over 5 generations, whereas abortive colony size distribution was robust against it. These results suggest that, whereas short-term RCD is critical to the abortive colony size distribution, long-lasting RCD is important for the dose response of the surviving fraction. CONCLUSIONS/SIGNIFICANCE: Our present model provides a single framework for understanding the behavior of primary cell colonies in culture following irradiation.

  8. Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells

    Science.gov (United States)

    Zhang, Hao; Tao, Yanling; Ren, Saisai; Liu, Haihui; Zhou, Hui; Hu, Jiangwei; Tang, Yongyong; Zhang, Bin; Chen, Hu

    2017-01-01

    Endothelial colony-forming cells (ECFCs) are a population of endothelial progenitor cells (EPCs) that display robust proliferative potential and vessel-forming capability. Previous studies have demonstrated that a limited number of ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord (UC) blood. The present study describes an effective method for isolating ECFCs from human UC. The ECFCs derived from human UC displayed the full properties of EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of the isolated human UC-ECFCs indicated that the cells demonstrated properties of stem cells, including relative stability and rapid proliferation in vitro. Gene expression of Fms related tyrosine kinase 1, kinase insert domain receptor, vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal growth factor homology domains-2, von Willebrand factor and endothelial nitric oxide synthase was assessed by reverse transcription-polymerase chain reaction. The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen-antigen D related protein according to flow cytometry. 1,1′-dioctadecyl-3,3,3′,3′-tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify the identity of the UC-ECFCs. Matrigel was used to investigate tube formation capability. The results demonstrated that the reported technique is a valuable method for isolating human UC-ECFCs, which have potential for use in vascular regeneration. PMID:29067104

  9. Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells.

    Science.gov (United States)

    Zhang, Hao; Tao, Yanling; Ren, Saisai; Liu, Haihui; Zhou, Hui; Hu, Jiangwei; Tang, Yongyong; Zhang, Bin; Chen, Hu

    2017-11-01

    Endothelial colony-forming cells (ECFCs) are a population of endothelial progenitor cells (EPCs) that display robust proliferative potential and vessel-forming capability. Previous studies have demonstrated that a limited number of ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord (UC) blood. The present study describes an effective method for isolating ECFCs from human UC. The ECFCs derived from human UC displayed the full properties of EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of the isolated human UC-ECFCs indicated that the cells demonstrated properties of stem cells, including relative stability and rapid proliferation in vitro. Gene expression of Fms related tyrosine kinase 1, kinase insert domain receptor, vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal growth factor homology domains-2, von Willebrand factor and endothelial nitric oxide synthase was assessed by reverse transcription-polymerase chain reaction. The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen-antigen D related protein according to flow cytometry. 1,1'-dioctadecyl-3,3,3',3'-tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify the identity of the UC-ECFCs. Matrigel was used to investigate tube formation capability. The results demonstrated that the reported technique is a valuable method for isolating human UC-ECFCs, which have potential for use in vascular regeneration.

  10. Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors.

    Science.gov (United States)

    Kawamura, Kazuhiro; Chen, Yuan; Shu, Yimin; Cheng, Yuan; Qiao, Jie; Behr, Barry; Pera, Renee A Reijo; Hsueh, Aaron J W

    2012-01-01

    Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility

  11. Recombinant GM-CSF/IL-3 fusion protein: its effect on in vitro human megakaryocytopoiesis.

    Science.gov (United States)

    Bruno, E; Briddell, R A; Cooper, R J; Brandt, J E; Hoffman, R

    1992-05-01

    An evaluation of the effectiveness of a genetically engineered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3) fusion protein (FP) as a means of delivering cytokine combinations to megakaryocyte (MK) progenitor cells was performed, utilizing a serum-depleted clonal assay system and a long-term bone marrow culture system. The effects of the FP, alone and in combination with a variety of other cytokines, on the primitive MK progenitor cell, the megakaryocyte burst-forming unit (BFU-MK), and the more differentiated megakaryocyte colony-forming unit (CFU-MK) were assessed. Subpopulations of bone marrow cells (CD34+ DR- for BFU-MK and CD34+ DR+ for CFU-MK) served as sources of these two classes of MK progenitor cells. The FP was equivalent to a combination of optimal concentrations of GM-CSF and IL-3 in promoting both the number and size of BFU-MK-derived colonies. The GM-CSF/IL-3 combination, however, promoted the formation of far greater CFU-MK-derived colonies than did the FP alone. The size of MK colonies formed in the presence of the FP or GM-CSF/IL-3 was similar. The ability of the FP to stimulate BFU-MK- but not CFU-MK-derived colony formation was also further augmented by the addition of interleukin 1 alpha (IL-1 alpha). The addition of c-kit ligand (KL) increased both FP-stimulated CFU-MK- and BFU-MK-derived colony numbers but only BFU-MK-derived colony size. In addition, the FP alone sustained long-term megakaryocytopoiesis in vitro to a level equivalent to that of the GM-CSF/IL-3 combination and was superior in this regard to either GM-CSF or IL-3 alone. These data indicate that FP is capable of supporting various stages of human megakaryocytopoiesis. We conclude that such genetically engineered molecules as the FP may prove to be effective means of pharmacologically delivering the biological effects of specific cytokine combinations.

  12. Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images.

    Science.gov (United States)

    Joutsijoki, Henry; Haponen, Markus; Rasku, Jyrki; Aalto-Setälä, Katriina; Juhola, Martti

    2016-01-01

    The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient's cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using a k-NN classifier showing improved accuracy compared to earlier studies.

  13. Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images

    Directory of Open Access Journals (Sweden)

    Henry Joutsijoki

    2016-01-01

    Full Text Available The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC colony images. iPS cell technology is a contemporary method by which the patient’s cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4% for classification was obtained by using a k-NN classifier showing improved accuracy compared to earlier studies.

  14. Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts.

    Science.gov (United States)

    Bengtsson, Torbjörn; Khalaf, Atika; Khalaf, Hazem

    2015-09-01

    Periodontal pathogens, including Porphyromonas gingivalis, can form biofilms in dental pockets and cause inflammation, which is one of the underlying mechanisms involved in the development of periodontal disease, ultimately leading to tooth loss. Although P. gingivalis is protected in the biofilm, it can still cause damage and modulate inflammatory responses from the host, through secretion of microvesicles containing proteinases. The aim of this study was to evaluate the role of cysteine proteinases in P. gingivalis colony growth and development, and subsequent immunomodulatory effects on human gingival fibroblast. By comparing the wild type W50 with its gingipain deficient strains we show that cysteine proteinases are required by P. gingivalis to form morphologically normal colonies. The lysine-specific proteinase (Kgp), but not arginine-specific proteinases (Rgps), was associated with immunomodulation. P. gingivalis with Kgp affected the viability of gingival fibroblasts and modulated host inflammatory responses, including induction of TGF-β1 and suppression of CXCL8 and IL-6 accumulation. These results suggest that secreted products from P. gingivalis, including proteinases, are able to cause damage and significantly modulate the levels of inflammatory mediators, independent of a physical host-bacterial interaction. This study provides new insight of the pathogenesis of P. gingivalis and suggests gingipains as targets for diagnosis and treatment of periodontitis. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. What's Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings.

    Science.gov (United States)

    Ruiz, Lorena; Espinosa-Martos, Irene; García-Carral, Cristina; Manzano, Susana; McGuire, Michelle K; Meehan, Courtney L; McGuire, Mark A; Williams, Janet E; Foster, James; Sellen, Daniel W; Kamau-Mbuthia, Elizabeth W; Kamundia, Egidioh W; Mbugua, Samwel; Moore, Sophie E; Kvist, Linda J; Otoo, Gloria E; Lackey, Kimberly A; Flores, Katherine; Pareja, Rossina G; Bode, Lars; Rodríguez, Juan M

    2017-01-01

    Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278.

  16. Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts.

    Science.gov (United States)

    van Laar, E S; Izbicka, E; Weitman, S; Medina-Gundrum, L; Macdonald, J R; Waters, S J

    2004-01-01

    The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 micro g /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.

  17. Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.

    Science.gov (United States)

    Tsai, Pei-Chin; Zhang, Zheng; Florek, Charles; Michniak-Kohn, Bozena B

    2016-01-01

    The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool.

  18. Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies.

    Science.gov (United States)

    Bhadriraju, Kiran; Halter, Michael; Amelot, Julien; Bajcsy, Peter; Chalfoun, Joe; Vandecreme, Antoine; Mallon, Barbara S; Park, Kye-Yoon; Sista, Subhash; Elliott, John T; Plant, Anne L

    2016-07-01

    Identification and quantification of the characteristics of stem cell preparations is critical for understanding stem cell biology and for the development and manufacturing of stem cell based therapies. We have developed image analysis and visualization software that allows effective use of time-lapse microscopy to provide spatial and dynamic information from large numbers of human embryonic stem cell colonies. To achieve statistically relevant sampling, we examined >680 colonies from 3 different preparations of cells over 5days each, generating a total experimental dataset of 0.9 terabyte (TB). The 0.5 Giga-pixel images at each time point were represented by multi-resolution pyramids and visualized using the Deep Zoom Javascript library extended to support viewing Giga-pixel images over time and extracting data on individual colonies. We present a methodology that enables quantification of variations in nominally-identical preparations and between colonies, correlation of colony characteristics with Oct4 expression, and identification of rare events. Copyright © 2016. Published by Elsevier B.V.

  19. Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies

    Directory of Open Access Journals (Sweden)

    Kiran Bhadriraju

    2016-07-01

    Full Text Available Identification and quantification of the characteristics of stem cell preparations is critical for understanding stem cell biology and for the development and manufacturing of stem cell based therapies. We have developed image analysis and visualization software that allows effective use of time-lapse microscopy to provide spatial and dynamic information from large numbers of human embryonic stem cell colonies. To achieve statistically relevant sampling, we examined >680 colonies from 3 different preparations of cells over 5 days each, generating a total experimental dataset of 0.9 terabyte (TB. The 0.5 Giga-pixel images at each time point were represented by multi-resolution pyramids and visualized using the Deep Zoom Javascript library extended to support viewing Giga-pixel images over time and extracting data on individual colonies. We present a methodology that enables quantification of variations in nominally-identical preparations and between colonies, correlation of colony characteristics with Oct4 expression, and identification of rare events.

  20. Human granulocyte colony stimulating factor (hG-CSF: cloning, overexpression, purification and characterization

    Directory of Open Access Journals (Sweden)

    Vanz Ana LS

    2008-04-01

    Full Text Available Abstract Background Biopharmaceutical drugs are mainly recombinant proteins produced by biotechnological tools. The patents of many biopharmaceuticals have expired, and biosimilars are thus currently being developed. Human granulocyte colony stimulating factor (hG-CSF is a hematopoietic cytokine that acts on cells of the neutrophil lineage causing proliferation and differentiation of committed precursor cells and activation of mature neutrophils. Recombinant hG-CSF has been produced in genetically engineered Escherichia coli (Filgrastim and successfully used to treat cancer patients suffering from chemotherapy-induced neutropenia. Filgrastim is a 175 amino acid protein, containing an extra N-terminal methionine, which is needed for expression in E. coli. Here we describe a simple and low-cost process that is amenable to scaling-up for the production and purification of homogeneous and active recombinant hG-CSF expressed in E. coli cells. Results Here we describe cloning of the human granulocyte colony-stimulating factor coding DNA sequence, protein expression in E. coli BL21(DE3 host cells in the absence of isopropyl-β-D-thiogalactopyranoside (IPTG induction, efficient isolation and solubilization of inclusion bodies by a multi-step washing procedure, and a purification protocol using a single cationic exchange column. Characterization of homogeneous rhG-CSF by size exclusion and reverse phase chromatography showed similar yields to the standard. The immunoassay and N-terminal sequencing confirmed the identity of rhG-CSF. The biological activity assay, in vivo, showed an equivalent biological effect (109.4% to the standard reference rhG-CSF. The homogeneous rhG-CSF protein yield was 3.2 mg of bioactive protein per liter of cell culture. Conclusion The recombinant protein expression in the absence of IPTG induction is advantageous since cost is reduced, and the protein purification protocol using a single chromatographic step should reduce cost

  1. Studies on Colony Stimulating Factor Receptor-1 and Ligands Colony Stimulating Factor-1 and Interleukin-34 in Alzheimer's Disease Brains and Human Microglia.

    Science.gov (United States)

    Walker, Douglas G; Tang, Tiffany M; Lue, Lih-Fen

    2017-01-01

    Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115) for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1) and the more recently identified interleukin-34 (IL-34). Studies of IL-34 activation of rodent microglia and human macrophages have suggested it has different properties to CSF-1, resulting in an anti-inflammatory reparative phenotype. The goal of this study was to identify if the responses of human postmortem brain microglia to IL-34 differed from their responses to CSF-1 with the aim of identifying different phenotypes of microglia as a result of their responses. To approach this question, we also sought to identify differences between IL-34, CSF-1, and CSF-1R expression in human brain samples to establish whether there was an imbalance in Alzheimer's disease (AD). Using human brain samples [inferior temporal gyrus (ITG) and middle temporal gyrus (MTG)] from distinct cohorts of AD, control and high pathology, or mild cognitive impairment cases, we showed that there was increased expression of CSF-1R and CSF-1 mRNAs in both series of AD cases, and reduced expression of IL-34 mRNA in AD ITG samples. There was no change in expression of these genes in RNA from cerebellum of AD, Parkinson's disease (PD), or control cases. The results suggested an imbalance in CSF-1R signaling in AD. Using RNA sequencing to compare gene expression responses of CSF-1 and IL-34 stimulated human microglia, a profile of responses to CSF-1 and IL-34 was identified. Contrary to earlier work with rodent microglia, IL-34 induced primarily a classical activation response similar to that of CSF-1. It was not possible to identify any genes expressed significantly different by IL-34-stimulated microglia compared to CSF-1-stimulated microglia, but both cytokines did induce certain

  2. Studies on Colony Stimulating Factor Receptor-1 and Ligands Colony Stimulating Factor-1 and Interleukin-34 in Alzheimer's Disease Brains and Human Microglia

    Directory of Open Access Journals (Sweden)

    Douglas G. Walker

    2017-08-01

    Full Text Available Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115 for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1 and the more recently identified interleukin-34 (IL-34. Studies of IL-34 activation of rodent microglia and human macrophages have suggested it has different properties to CSF-1, resulting in an anti-inflammatory reparative phenotype. The goal of this study was to identify if the responses of human postmortem brain microglia to IL-34 differed from their responses to CSF-1 with the aim of identifying different phenotypes of microglia as a result of their responses. To approach this question, we also sought to identify differences between IL-34, CSF-1, and CSF-1R expression in human brain samples to establish whether there was an imbalance in Alzheimer's disease (AD. Using human brain samples [inferior temporal gyrus (ITG and middle temporal gyrus (MTG] from distinct cohorts of AD, control and high pathology, or mild cognitive impairment cases, we showed that there was increased expression of CSF-1R and CSF-1 mRNAs in both series of AD cases, and reduced expression of IL-34 mRNA in AD ITG samples. There was no change in expression of these genes in RNA from cerebellum of AD, Parkinson's disease (PD, or control cases. The results suggested an imbalance in CSF-1R signaling in AD. Using RNA sequencing to compare gene expression responses of CSF-1 and IL-34 stimulated human microglia, a profile of responses to CSF-1 and IL-34 was identified. Contrary to earlier work with rodent microglia, IL-34 induced primarily a classical activation response similar to that of CSF-1. It was not possible to identify any genes expressed significantly different by IL-34-stimulated microglia compared to CSF-1-stimulated microglia, but both cytokines did induce

  3. Sarcoptes scabiei mites modulate gene expression in human skin equivalents.

    Directory of Open Access Journals (Sweden)

    Marjorie S Morgan

    Full Text Available The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin's protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host's protective response allowing these mites to survive in the skin.

  4. [Airborne fine particle decreases the cell viability and induces inflammation in human bronchial epithelial cells].

    Science.gov (United States)

    Hong, Zhicong; Luo, Xianyang; Cai, Chengfu; Xu, Jian; Zhuang, Guoshun

    2017-09-28

    To investigate the effects of airborne fine particle on cell viability and inflammation in human bronchial epithelial cells.
 Methods: Atmospheric PM2.5 samples were collected by PM2.5 sampler. PM2.5 morphology was observed by scanning electron microscope (SEM). Human bronchial epithelial cells (BEAS-2B) were treated with PM2.5 at different concentrations (0, 50, 100, 200, 400, 800 μg/mL) for 12, 24 or 48 hours, and the cell activity were evaluated by cell counting kit-8 (CCK-8). The mRNA expression levels of (granulocyte-macrophage colony stimulating factor,GM-CSF) and TNF-α were detected by quantitative real-time PCR (qRT-PCR). Western blot was used to detect the protein expressions of GM-CSF and TNF-α.
 Results: According to SEM, the shape of PM2.5 varied, and the diameter was different and mostly equal to or less than 2.5 μm. CCK-8 assay showed that different concentrations of PM2.5 exposure for 12 hours, 24 hours and 48 hours resulted in loss of cell viability of BEAS-2B cells (P<0.05). Different concentrations of PM2.5 increased the mRNA and protein expression of GM-CSF and TNF-α, and the higher concentration of PM2.5 induced higher expression, which have statistical significant difference between the groups (P<0.05).
 Conclusion: Atmospheric PM2.5 can cause inflammatory response in human bronchial epithelial cells. They can reduce cell viability, which may be related to the PM2.5 trigger and aggravation of bronchopulmonary inflammatory diseases.

  5. Human myelopoiesis in culture of liquid medium lacking colony stimulating factors: therapeutic implications for cancer patients with leukopenia.

    Science.gov (United States)

    Diamandopoulos, G T

    1994-01-01

    Patients with cancer often develop leukopenia caused by chemotherapy. Since their treatment with human colony stimulating factors (CSFs) has limitations, it is imperative to determine if CSFs are essential in regulating human myelopoiesis. For this purpose, human primary precursor myeloid cells were cultured in media lacking exogenous human CSFs and stem cell factor (SCF), and supplemented with human sera, or with fetal bovine or other types of animal sera. Cells cultured in human sera survive well, proliferate actively, and differentiate toward granulocytes. Most cells cultured in fetal bovine serum die, few differentiate toward monocytes-macrophages. Cells cultured in other types of animal sera die rapidly. Antibodies neutralizing human serum's CSFs and SCF do not abolish its myeloregulatory activity. It is concluded that cell growth factors other than CSFs and SCF present in human serum regulate human myelopoiesis in vitro. These findings bear important therapeutic implication for patients with cancer having leukopenia.

  6. Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know?

    Science.gov (United States)

    Pessach, Ilias; Shimoni, Avichai; Nagler, Arnon

    2013-01-01

    BACKGROUND Hematopoietic growth factors (HGFs) are mostly used as supportive measures to reduce infectious complications associated with neutropenia. Over the past decade, the use of HGFs became a common method for mobilizing human CD34+ stem cells, either for autologous or allogeneic transplantation. However, since their introduction the long-term safety of the procedure has become a major focus of discussion and research. Most information refers to healthy normal donors and data concerning pregnant and lactating women are scarce. The clinical question, which is the core of this review, is whether stem cell donation, preceded by administration of granulocyte-colony stimulating factor (G-CSF) for mobilization, is a safe procedure for pregnant donors. METHODS Literature searches were performed in Pubmed for English language articles published before the end of May 2012, focusing on G-CSF administration during pregnancy, lactation and hematopoietic stem cell donation. Searches included animal and human studies. RESULTS Data from animals (n = 15 studies) and women (n = 46 studies) indicate that G-CSF crosses the placenta, stimulates fetal granulopoiesis, improves neonatal survival mostly for very immature infants, promotes trophoblast growth and placental metabolism and has an anti-abortive role. Granulocyte macrophage-CSF is a key cytokine in the maternal immune tolerance towards the implanted embryo and exerts protective long-term programming effects to preimplantation embryos. The available data suggest that probably CSFs should not be administered during the time of most active organogenesis (first trimester), except perhaps for the first week during which implantation takes place. Provided CSF is administered during the second and third trimesters, it appears to be safe, and pregnant women receiving the CSF treatment can become hematopoietic stem cell donors. There are also risks related to the anesthesia, which is required for the bone marrow aspiration. During

  7. Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells.

    Science.gov (United States)

    Boland, S; Bonvallot, V; Fournier, T; Baeza-Squiban, A; Aubier, M; Marano, F

    2000-01-01

    We have previously shown that exposure to diesel exhaust particles (DEPs) stimulates human airway epithelial cells to secrete the inflammatory cytokines interleukin-8, interleukin-1beta, and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in allergic diseases. In the present paper, we studied the mechanisms underlying the increase in GM-CSF release elicited by DEPs using the human bronchial epithelial cell line 16HBE14o-. RT-PCR analysis has shown an increase in GM-CSF mRNA levels after DEP treatments. Comparison of the effects of DEPs, extracted DEPs, or extracts of DEPs has shown that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and not to the metals present on the DEP surface because the metal chelator desferrioxamine had no inhibitory effect. Furthermore, radical scavengers inhibited the DEP-induced GM-CSF release, showing involvement of reactive oxygen species in this response. Moreover genistein, a tyrosine kinase inhibitor, abrogated the effects of DEPs on GM-CSF release, whereas protein kinase (PK) C, PKA, cyclooxygenase, or lipoxygenase inhibitors had no effect. PD-98059, an inhibitor of mitogen-activated protein kinase, diminished the effects of DEPs, whereas SB-203580, an inhibitor of p38 mitogen-activated protein kinase, had a lower effect, and DEPs did actually increase the active, phosphorylated form of the extracellular signal-regulated kinase as shown by Western blotting. In addition, cytochalasin D, which inhibits the phagocytosis of DEPs, reduced the increase in GM-CSF release after DEP treatment. Together, these data suggest that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and that the effect of native DEPs requires endocytosis of the particles. Reactive oxygen species and tyrosine kinase(s) may be involved in the DEP-triggered signaling of the GM-CSF response.

  8. Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells.

    Science.gov (United States)

    Mazzola, Maria Antonietta; Raheja, Radhika; Regev, Keren; Beynon, Vanessa; von Glehn, Felipe; Paul, Anu; Pierre, Isabelle; Kivisakk, Pia; Weiner, Howard L; Gandhi, Roopali

    2017-11-01

    Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. To investigate the role of MMF on human mDCs maturation and function. mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR. MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells. We report that MMF can modulate immune response by affecting human mDC function.

  9. An in vitro-differentiated human cell line as a model system to study the interaction of Neisseria gonorrhoeae with phagocytic cells.

    Science.gov (United States)

    Hauck, C R; Lorenzen, D; Saas, J; Meyer, T F

    1997-05-01

    The extreme host specificity of pathogenic neisseriae limits investigations aimed at the analysis of bacterial-host interactions almost completely to the use of in vitro models. Although permanent epithelial and endothelial cell lines are already indispensable tools with respect to initial infection processes, studies concerning the interaction of neisseriae with phagocytic cells have been confined to primary human blood cells. We investigated the use of human leukemia-derived monocytic and myelomonocytic cell lines that can be differentiated in vitro towards phagocytic cells by a panel of chemical and biological reagents including cytokines, vitamin analogs, and antileukemia drugs. Whereas tumor necrosis factor alpha, gamma interferon, bufalin, or granulocyte-macrophage colony-stimulating factor only marginally increased the ability of monocytic MonoMac-6 and myelomonocytic JOSK-M cells to interact with the bacteria, retinoic acid and vitamin D3 treatment for 2 to 4 days led to highly phagocytic cells that internalized gonococci in an Opa protein-specific manner. This is comparable to the phagocytosis by primary monocytes from human blood, where more than 80% of cells are infected with intracellular bacteria. The increased phagocytic activity of JOSK-M cells following in vitro differentiation was paralleled by enhanced oxidative burst capacity. Whereas undifferentiated cells responded to neither phorbol 12-myristate 13-acetate nor other known soluble and particulate stimuli, cells incubated with retinoic acid and bufalin showed the same pattern and the same intensity of oxidative burst activity in response to Neisseria gonorrhoeae as primary cells: Opa-expressing gonococci elicited an oxidative burst, whereas Opa- gonococci did not. The surface expression of major histocompatibility complex (MHC) class II molecules was only slightly changed after retinoic acid treatment. Also, phagocytosis of gonococci had no influence on MHC class II surface expression. Taken

  10. Clinical role of GM-CSF in neutrophil recovery in relation to health care parameters

    NARCIS (Netherlands)

    Hofstra, LS; DeVries, EGE; UylDeGroot, CA; Vellenga, E

    Recombinant human growth factors, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF), have been only available for a few years. Since their introduction they have affected the management of drug-induced neutropenia, the use of dose intensive chemotherapy regimens and in the

  11. A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

    DEFF Research Database (Denmark)

    Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune

    2015-01-01

    PURPOSE: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony...

  12. Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF, and IL12

    Energy Technology Data Exchange (ETDEWEB)

    Parney, I.F.; Farr-Jones, M.A. [Univ. of Alberta, Div. of Neurosurgery, Edmonton, Alberta (Canada); Kane, K.; Chang, L.-J. [Univ. of Alberta, Dept. of Surgery and Dept. of Medical Microbiology and Immunology, Edmonton, Alberta (Canada); Petruk, K.C. [Univ. of Alberta, Div. of Neurosurgery, Edmonton, Alberta (Canada)

    2002-08-01

    Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 ({sup 51}Cr) release assay. Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2,GM-CSF,and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of turnor subclones with limited antigenic spectra during retrovirus-mediated gene transfer. (author)

  13. Prevalence of Streptococcus mutans with different colonial morphologies in human plaque and saliva.

    Science.gov (United States)

    Emilson, C G

    1983-02-01

    Plaque and saliva samples were obtained twice from 58 children at an interval of 1 year and examined for the prevalence of Streptococcus mutans on Mitis salivarius (MS) and Mitis salivarius bacitracin (MSB) agar. Two types of S. mutans colonies with different colonial morphologies were seen on both media. They were serologically identified as serotypes c/e/f and d/g respectively. The first type, morphogroup c/e/f, had the typical "frosted-glass" appearance. It was the most prevalent and was found in 97% of the children. The second type, morphogroup d/g, had a creamy marzipan consistency with a dull, granular surface, gray to brown in color and often with some liquid around or on top of the colony. Group d/g was detected in 21 children (36%) and then together with colonies of group c/e/f. Children infected with single or multiple morphogroups of S. mutans generally harbored the same groups 1 year later. There was a significant positive correlation between the proportion of S. mutans in plaque and their numbers in saliva.

  14. Analysis of Mitochondrial Transfer in Direct Co-cultures of Human Monocyte-derived Macrophages (MDM) and Mesenchymal Stem Cells (MSC).

    Science.gov (United States)

    Jackson, Megan V; Krasnodembskaya, Anna D

    2017-05-05

    Mesenchymal stem/stromal cells (MSC) are adult stem cells which have been shown to improve survival, enhance bacterial clearance and alleviate inflammation in pre-clinical models of acute respiratory distress syndrome (ARDS) and sepsis. These diseases are characterised by uncontrolled inflammation often underpinned by bacterial infection. The mechanisms of MSC immunomodulatory effects are not fully understood yet. We sought to investigate MSC cell contact-dependent communication with alveolar macrophages (AM), professional phagocytes which play an important role in the lung inflammatory responses and anti-bacterial defence. With the use of a basic direct co-culture system, confocal microscopy and flow cytometry we visualised and effectively quantified MSC mitochondrial transfer to AM through tunnelling nanotubes (TNT). To model the human AM, primary monocytes were isolated from human donor blood and differentiated into macrophages (monocyte derived macrophages, MDM) in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF), thus allowing adaptation of an AM-like phenotype (de Almeida et al., 2000; Guilliams et al., 2013). Human bone-marrow derived MSC, were labelled with mitochondria-specific fluorescent stain, washed extensively, seeded into the tissue culture plate with MDMs at the ratio of 1:20 (MSC/MDM) and co-cultured for 24 h. TNT formation and mitochondrial transfer were visualised by confocal microscopy and semi-quantified by flow cytometry. By using the method we described here we established that MSC use TNTs as the means to transfer mitochondria to macrophages. Further studies demonstrated that mitochondrial transfer enhances macrophage oxidative phosphorylation and phagocytosis. When TNT formation was blocked by cytochalasin B, MSC effect on macrophage phagocytosis was completely abrogated. This is the first study to demonstrate TNT-mediated mitochondrial transfer from MSC to innate immune cells.

  15. Altered Proteome of Burkholderia pseudomallei Colony Variants Induced by Exposure to Human Lung Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Anis Rageh Al-Maleki

    Full Text Available Burkholderia pseudomallei primary diagnostic cultures demonstrate colony morphology variation associated with expression of virulence and adaptation proteins. This study aims to examine the ability of B. pseudomallei colony variants (wild type [WT] and small colony variant [SCV] to survive and replicate intracellularly in A549 cells and to identify the alterations in the protein expression of these variants, post-exposure to the A549 cells. Intracellular survival and cytotoxicity assays were performed followed by proteomics analysis using two-dimensional gel electrophoresis. B. pseudomallei SCV survive longer than the WT. During post-exposure, among 259 and 260 protein spots of SCV and WT, respectively, 19 were differentially expressed. Among SCV post-exposure up-regulated proteins, glyceraldehyde 3-phosphate dehydrogenase, fructose-bisphosphate aldolase (CbbA and betaine aldehyde dehydrogenase were associated with adhesion and virulence. Among the down-regulated proteins, enolase (Eno is implicated in adhesion and virulence. Additionally, post-exposure expression profiles of both variants were compared with pre-exposure. In WT pre- vs post-exposure, 36 proteins were differentially expressed. Of the up-regulated proteins, translocator protein, Eno, nucleoside diphosphate kinase (Ndk, ferritin Dps-family DNA binding protein and peptidyl-prolyl cis-trans isomerase B were implicated in invasion and virulence. In SCV pre- vs post-exposure, 27 proteins were differentially expressed. Among the up-regulated proteins, flagellin, Eno, CbbA, Ndk and phenylacetate-coenzyme A ligase have similarly been implicated in adhesion, invasion. Protein profiles differences post-exposure provide insights into association between morphotypic and phenotypic characteristics of colony variants, strengthening the role of B. pseudomallei morphotypes in pathogenesis of melioidosis.

  16. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis.

    Science.gov (United States)

    Constantinescu, Cris S; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E; Sprenger, Till; Radue, Ernst W

    2015-08-01

    To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.

  17. Molecular basis of in vitro affinity maturation and functional evolution of a neutralizing anti-human GM-CSF antibody.

    Science.gov (United States)

    Eylenstein, Roy; Weinfurtner, Daniel; Härtle, Stefan; Strohner, Ralf; Böttcher, Jark; Augustin, Martin; Ostendorp, Ralf; Steidl, Stefan

    2016-01-01

    X-ray structure analysis of 4 antibody Fab fragments, each in complex with human granulocyte macrophage colony stimulating factor (GM-CSF), was performed to investigate the changes at the protein-protein binding interface during the course of in vitro affinity maturation by phage display selection. The parental antibody MOR03929 was compared to its derivatives MOR04252 (CDR-H2 optimized), MOR04302 (CDR-L3 optimized) and MOR04357 (CDR-H2 and CDR-L3 optimized). All antibodies bind to a conformational epitope that can be divided into 3 sub-epitopes. Specifically, MOR04357 binds to a region close to the GM-CSF N-terminus (residues 11-24), a short second sub-epitope (residues 83-89) and a third at the C-terminus (residues 112-123). Modifications introduced during affinity maturation in CDR-H2 and CDR-L3 led to the establishment of additional hydrogen bonds and van der Waals contacts, respectively, providing a rationale for the observed improvement in binding affinity and neutralization potency. Once GM-CSF is complexed to the antibodies, modeling predicts a sterical clash with GM-CSF binding to GM-CSF receptor α and β chain. This predicted mutually exclusive binding was confirmed by a GM-CSF receptor α chain ligand binding inhibition assay. Finally, high throughput sequencing of clones obtained after affinity maturation phage display pannings revealed highly selected consensus sequences for CDR-H2 as well for CDR-L3, which are in accordance with the sequence of the highest affinity antibody MOR04357. The resolved crystal structures highlight the criticality of these strongly selected residues for high affinity interaction with GM-CSF.

  18. Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension

    Science.gov (United States)

    Sawada, Hirofumi; Saito, Toshie; Nickel, Nils P.; Alastalo, Tero-Pekka; Glotzbach, Jason P.; Chan, Roshelle; Haghighat, Leila; Fuchs, Gabriele; Januszyk, Michael; Cao, Aiqin; Lai, Ying-Ju; Perez, Vinicio de Jesus; Kim, Yu-Mee; Wang, Lingli; Chen, Pin-I; Spiekerkoetter, Edda; Mitani, Yoshihide; Gurtner, Geoffrey C.; Sarnow, Peter

    2014-01-01

    Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34–PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor α (GM-CSFRα)–positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH. PMID:24446489

  19. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

    Directory of Open Access Journals (Sweden)

    M.O. Diniz

    2011-05-01

    Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  20. Human umbilical cord blood plasma can replace fetal bovine serum for in vitro expansion of functional human endothelial colony-forming cells.

    Science.gov (United States)

    Huang, Lan; Critser, Paul J; Grimes, Brenda R; Yoder, Mervin C

    2011-07-01

    A hierarchy of endothelial colony-forming cells (ECFC) with different levels of proliferative potential has been identified in human circulating blood and blood vessels. ECFC has recently become an attractive target for new vascular regenerative therapies; however, in vitro expansion of ECFC typically depends on the presence of fetal bovine serum (FBS) or fetal calf serum (FCS) in the culture medium, which is not appropriate for its therapeutic application. To identify optimal conditions for in vitro expansion of ECFC, the effects of human endothelial serum-free medium (SFM) supplemented with six pro-angiogenic cytokines and human umbilical cord blood plasma (HCP) were investigated. The in vitro morphology, proliferation, surface antigen expression and in vivo vessel-forming ability were utilized for examining the effects of medium on ECFC. This novel formulation of endothelial cell culture medium allows us, for the first time, to isolate and expand human ECFC efficiently in vitro with a low concentration of HCP (1.5%) and without bovine serum additives. In this serum-reduced medium (SRM), human ECFC colony yields remained quantitatively similar to those cultured in a high concentration (10%) of bovine serum-supplemented medium. SRM-cultured ECFC displayed a robust clonal proliferative ability in vitro and human vessel-forming capacity in vivo. The present study provides a novel method for the expansion of human ECFC in vitro and will help to advance approaches for using the cells in human therapeutic trials.

  1. Primary cultured fibroblasts derived from patients with chronic wounds: a methodology to produce human cell lines and test putative growth factor therapy such as GMCSF

    Directory of Open Access Journals (Sweden)

    Coppock Donald L

    2008-12-01

    Full Text Available Abstract Background Multiple physiologic impairments are responsible for chronic wounds. A cell line grown which retains its phenotype from patient wounds would provide means of testing new therapies. Clinical information on patients from whom cells were grown can provide insights into mechanisms of specific disease such as diabetes or biological processes such as aging. The objective of this study was 1 To culture human cells derived from patients with chronic wounds and to test the effects of putative therapies, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF on these cells. 2 To describe a methodology to create fibroblast cell lines from patients with chronic wounds. Methods Patient biopsies were obtained from 3 distinct locations on venous ulcers. Fibroblasts derived from different wound locations were tested for their migration capacities without stimulators and in response to GM-CSF. Another portion of the patient biopsy was used to develop primary fibroblast cultures after rigorous passage and antimicrobial testing. Results Fibroblasts from the non-healing edge had almost no migration capacity, wound base fibroblasts were intermediate, and fibroblasts derived from the healing edge had a capacity to migrate similar to healthy, normal, primary dermal fibroblasts. Non-healing edge fibroblasts did not respond to GM-CSF. Six fibroblast cell lines are currently available at the National Institute on Aging (NIA Cell Repository. Conclusion We conclude that primary cells from chronic ulcers can be established in culture and that they maintain their in vivo phenotype. These cells can be utilized for evaluating the effects of wound healing stimulators in vitro.

  2. A novel and simple method for the generation of functional human dendritic cells from unfractionated peripheral blood mononuclear cells within 2 days: its application for induction of HIV-1-reactive CD4+ T cells in the hu-PBL SCID mice

    Directory of Open Access Journals (Sweden)

    Akira eKodama

    2013-09-01

    Full Text Available Because dendritic cells (DCs play a critical role in the regulation of adaptive immune responses, they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. Generally, monocyte-derived DCs (MDDCs were generated from purified monocytes by multiple steps of time-consuming physical manipulations for an extended period cultivation. In this study, we developed a novel, simple and rapid method for the generation of type-1 helper T cell (Th1-stimulating human DCs directly from bulk peripheral blood mononuclear cells (PBMCs. PBMCs were cultivated in the presence of 20 ng/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF, 20 ng/ml of interleukin-4 (IL-4 and 1,000 U/ml of interferon-β (IFN-β for 24 hours followed by 24 hour maturation with a cytokine cocktail containing 10 ng/ml of tumor necrosis factor-α (TNF-α, 10 ng/ml of IL-1β and 1 μg/ml of prostaglandin E2 (PGE2. The phenotype and biological activity of these new DCs for induction of allogeneic T cell proliferation and cytokine production were comparable to those of the MDDCs. Importantly, these new DCs pulsed with inactivated HIV-1 could generated HIV-1-reactive CD4+ T cell responses in humanized mice reconstituted with autologous PBMCs from HIV-1-negative donors. This simple and quick method for generation of functional DCs will be useful for future studies on DC-mediated immunotherapies.

  3. Diet and gender in the Tiwanaku colonies: Stable isotope analysis of human bone collagen and apatite from Moquegua, Peru.

    Science.gov (United States)

    Somerville, Andrew D; Goldstein, Paul S; Baitzel, Sarah I; Bruwelheide, Karin L; Dahlstedt, Allisen C; Yzurdiaga, Linda; Raubenheimer, Sarah; Knudson, Kelly J; Schoeninger, Margaret J

    2015-11-01

    Gender and other facets of social identity play important roles in the organization of complex societies. This study reconstructs dietary practices within the Middle Horizon (AD 500-1000) Tiwanaku colonies in southern Peru to increase our knowledge of gendered patterns of consumption within this early expansive state. We use stable isotope analysis of 43 human bone samples representing 14 females, 20 males, 8 juveniles, and 1 indeterminate individual recovered from burial excavations at the sites of Rio Muerto and Omo in the Moquegua Valley. Data are contextualized by comparisons with previously published Tiwanaku isotope data from the period. Our results find mean values of δ(13) Capatite = -7.3 ± 1.6% (N = 36, 1SD), δ(13) Ccollagen  = -12.3 ± 1.5% (N = 43, 1SD), and δ(15) Ncollagen  = 8.4 ± 1.6% (N = 43, 1SD). Between the sexes, Mann-Whitney U tests demonstrate significant differences in δ(13) Ccollagen (U = 74, P = 0.021), but no differences in δ(13) Capatite (U = 58, P = 0.095) or δ(15) Ncollagen (U = 116, P = 0.755) values. These data indicate relatively high C4 plant consumption among the Tiwanaku colonies, and support paleobotanical and archaeological evidence that maize (Zea mays) was the staple crop. Dietary values are similar overall between the sexes, but significantly higher δ(13) Ccollagen values in males is consistent with a model of gendered norms of consumption similar to that of the later Inca (AD 1438-1533), where males consumed more maize than females, often in the form of beer (chicha). Results provide new insights on social dynamics within the Tiwanaku colonies and suggest the increased importance maize consumption for males during the Tiwanaku expansion. © 2015 Wiley Periodicals, Inc.

  4. Uterine Vasculature Remodeling in Human Pregnancy Involves Functional Macrochimerism by Endothelial Colony Forming Cells of Fetal Origin

    Science.gov (United States)

    Sipos, Peter I; Rens, Willem; Schlecht, HÉlène; Fan, Xiaohu; Wareing, Mark; Hayward, Christina; Hubel, Carl A; Bourque, Stephane; Baker, Philip N; Davidge, Sandra T; Sibley, Colin P; Crocker, Ian P

    2013-01-01

    The potency of adult-derived circulating progenitor endothelial colony forming cells (ECFCs) is drastically surpassed by their fetal counterparts. Human pregnancy is associated with robust intensification of blood flow and vascular expansion in the uterus, crucial for placental perfusion and fetal supply. Here, we investigate whether fetal ECFCs transmigrate to maternal bloodstream and home to locations of maternal vasculogenesis, primarily the pregnant uterus. In the first instance, endothelial-like cells, originating from mouse fetuses expressing paternal eGFP, were identified within uterine endothelia. Subsequently, LacZ or enhanced green fluorescent protein (eGFP)-labeled human fetal ECFCs, transplanted into immunodeficient (NOD/SCID) fetuses on D15.5 pregnancy, showed similar integration into the mouse uterus by term. Mature endothelial controls (human umbilical vein endothelial cells), similarly introduced, were unequivocally absent. In humans, SRY was detected in 6 of 12 myometrial microvessels obtained from women delivering male babies. The copy number was calculated at 175 [IQR 149–471] fetal cells per millimeter square endothelium, constituting 12.5% of maternal vessel lumina. Cross-sections of similar human vessels, hybridized for Y-chromosome, positively identified endothelial-associated fetal cells. It appears that through ECFC donation, fetuses assist maternal uterine vascular expansion in pregnancy, potentiating placental perfusion and consequently their own fetal supply. In addition to fetal growth, this cellular mechanism holds implications for materno-fetal immune interactions and long-term maternal vascular health. PMID:23554274

  5. Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation.

    Science.gov (United States)

    Noble, Amanda R; Maitland, Norman J; Berney, Daniel M; Rumsby, Martin G

    2018-01-01

    Phospholipases D1 and D2 (PLD1/2) hydrolyse cell membrane glycerophospholipids to generate phosphatidic acid, a signalling lipid, which regulates cell growth and cancer progression through effects on mTOR and PKB/Akt. PLD expression and/or activity is raised in breast, colorectal, gastric, kidney and thyroid carcinomas but its role in prostate cancer (PCa), the major cancer of men in the western world, is unclear. PLD1 protein expression in cultured PNT2C2, PNT1A, P4E6, LNCaP, PC3, PC3M, VCaP, 22RV1 cell lines and patient-derived PCa cells was analysed by western blotting. PLD1 protein localisation in normal, benign prostatic hyperplasia (BPH), and castrate-resistant prostate cancer (CRPC) tissue sections and in a PCa tissue microarray (TMA) was examined by immunohistochemistry. PLD activity in PCa tissue was assayed using an Amplex Red method. The effect of PLD inhibitors on PCa cell viability was measured using MTS and colony forming assays. PLD1 protein expression was low in the luminal prostate cell lines (LNCaP, VCaP, 22RV1) compared with basal lines (PC3 and PC3M). PLD1 protein expression was elevated in BPH biopsy tissue relative to normal and PCa samples. In normal and BPH tissue, PLD1 was predominantly detected in basal cells as well in some stromal cells, rather than in luminal cells. In PCa tissue, luminal cells expressed PLD1. In a PCa TMA, the mean peroxidase intensity per DAB-stained Gleason 6 and 7 tissue section was significantly higher than in sections graded Gleason 9. In CRPC tissue, PLD1 was expressed prominently in the stromal compartment, in luminal cells in occasional glands and in an expanding population of cells that co-expressed chromogranin A and neurone-specific enolase. Levels of PLD activity in normal and PCa tissue samples were similar. A specific PLD1 inhibitor markedly reduced the survival of both prostate cell lines and patient-derived PCa cells compared with two dual PLD1/PLD2 inhibitors. Short-term exposure of PCa cells to the

  6. Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study.

    Science.gov (United States)

    Nefussy, Beatrice; Artamonov, Irena; Deutsch, Varda; Naparstek, Ela; Nagler, Arnon; Drory, Vivian E

    2010-01-01

    Granulocyte-colony stimulating factor (G-CSF) is used to mobilize CD34+ haematopoietic stem cells from the bone marrow to the peripheral blood. We proposed to use cell subsets induced by G-CSF to slow down disease progression in patients with amyotrophic lateral sclerosis (ALS). Patients with definite or probable ALS were assigned in a double-blind manner to receive G-CSF or placebo every three months for a year. The primary outcome measure was the functional decline, measured by the revised ALS Functional Rating Scale, Revised (ALSFRS-R) score. Secondary outcome measures included vital capacity, manual muscle strength, compound muscle action potential amplitudes, neurophysiological index, and McGill single item quality of life score (QoL). Thirty-nine patients were enrolled. Seventeen patients who received G-CSF and 18 who received placebo were evaluated. G-CSF was effective in mobilizing CD34+ to blood. The outcome measures used showed no statistically significant benefit, although there was a trend of slowing disease progression following two G-CSF treatments, as shown by lower slopes of ALSFRS-R and QoL in the first six treatment months. The treatment had no major side-effects. G-CSF administration in ALS patients caused successful mobilization of autologous bone marrow cells, but was not effective in slowing down disease deterioration.

  7. Use of colony-based bacterial strain typing for tracking the fate of Lactobacillus strains during human consumption

    Directory of Open Access Journals (Sweden)

    Drevinek Pavel

    2009-12-01

    Full Text Available Abstract Background The Lactic Acid Bacteria (LAB are important components of the healthy gut flora and have been used extensively as probiotics. Understanding the cultivable diversity of LAB before and after probiotic administration, and being able to track the fate of administered probiotic isolates during feeding are important parameters to consider in the design of clinical trials to assess probiotic efficacy. Several methods may be used to identify bacteria at the strain level, however, PCR-based methods such as Random Amplified Polymorphic DNA (RAPD are particularly suited to rapid analysis. We examined the cultivable diversity of LAB in the human gut before and after feeding with two Lactobacillus strains, and also tracked the fate of these two administered strains using a RAPD technique. Results A RAPD typing scheme was developed to genetically type LAB isolates from a wide range of species, and optimised for direct application to bacterial colony growth. A high-throughput strategy for fingerprinting the cultivable diversity of human faeces was developed and used to determine: (i the initial cultivable LAB strain diversity in the human gut, and (ii the fate of two Lactobacillus strains (Lactobacillus salivarius NCIMB 30211 and Lactobacillus acidophilus NCIMB 30156 contained within a capsule that was administered in a small-scale human feeding study. The L. salivarius strain was not cultivated from the faeces of any of the 12 volunteers prior to capsule administration, but appeared post-feeding in four. Strains matching the L. acidophilus NCIMB 30156 feeding strain were found in the faeces of three volunteers prior to consumption; after taking the Lactobacillus capsule, 10 of the 12 volunteers were culture positive for this strain. The appearance of both Lactobacillus strains during capsule consumption was statistically significant (p Conclusion We have shown that genetic strain typing of the cultivable human gut microbiota can be

  8. M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae

    Science.gov (United States)

    Buchacher, Tanja; Ohradanova-Repic, Anna; Stockinger, Hannes

    2015-01-01

    Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-γ and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72±5% of M2 vs. 48±7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence

  9. Effects of human distrubance on a red-faced cormorant colony 1/

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Presented at Fifth Annual Meeting of the Pacific Seabird Group, Asilomar, California, December 13-16, 1978. The effects of human disturbance on nesting Red-faced...

  10. The Antiproliferative and Colony-suppressive Activities of STAT3 Inhibitors in Human Cancer Cells Is Compromised Under Hypoxic Conditions.

    Science.gov (United States)

    Tian, Jilai; Xiao, Hui; Wu, Ruohan; Cao, Yang; Li, Chenglong; Xu, Ronald; Pierson, Christopher R; Finlay, Jonathan L; Yang, Fang; Gu, Ning; Lin, Jiayuh

    2017-02-01

    Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors. To examine this, two STAT3 inhibitors were tested to investigate their inhibitory efficacy in cancer cells grown under hypoxic conditions compared with those without hypoxia. Cell proliferation, colony formation and western blot assays were performed to examine the differences in the cell viability, proliferation and proteins in the STAT3 pathway. Under hypoxic conditions, the half-maximal inhibitory concentration values for both STAT3 inhibitors were increased compared to normoxic conditions in human pancreatic cancer, medulloblastoma and sarcoma cell lines. In addition, the ability of both STAT3 inhibitors to inhibit colony formation in pancreatic cancer, medulloblastoma and sarcoma cell lines was reduced under hypoxic conditions when compared to cells under normoxic conditions. Furthermore, there was an increase in phosphorylated STAT3 levels in cancer cells under hypoxic conditions, suggesting this may be one of the mechanisms of resistance. In summary, the results presented here provide a novel finding of STAT3 inhibitor activity under hypoxic conditions and indicate that under such low oxygen conditions, the anticancer efficacy of STAT3 inhibitors was indeed hampered. These results highlight the need to develop new therapeutic strategies to overcome the resistance of cancer cells to STAT3 inhibitors under hypoxic conditions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor.

    Science.gov (United States)

    Briddell, R A; Broudy, V C; Bruno, E; Brandt, J E; Srour, E F; Hoffman, R

    1992-06-15

    A mouse antihuman monoclonal IgG2a antibody, termed stem cell receptor-1 (SR-1), specific for a determinant of the c-kit ligand receptor (KR), was used as an immunologic probe to analyze KR expression by human bone marrow hematopoietic progenitor cells. Monoclonal antibodies to CD34 and HLA-DR were used in a multicolor staining protocol in conjunction with SR-1 to further define the phenotypes of various classes of hematopoietic progenitor cells. Expression of KR (SR-1+) on hematopoietic progenitor cells identified subpopulations of cells expressing CD34 (CD34+). While one-half of the CD34- and HLA-DR-expressing cells (CD34+ HLA-DR+) expressed the KR (SR-1+), one-third of the CD34+ cells that lacked HLA-DR expression (CD34+ HLA-DR-) were SR-1+. The CD34+ HLA-DR+ SR-1+ cell population contained the vast majority of the more differentiated progenitor cells, including the colony-forming unit (CFU) granulocyte-macrophage; burst-forming unit-erythrocyte; CFU-granulocyte, erythrocyte, macrophage, megakaryocyte; and the CFU-megakaryocyte. The overall progenitor cell cloning efficiency of this subpopulation was greater than 31%. By contrast, the CD34+ HLA-DR- SR-1+ cell population contained fewer of these more differentiated progenitor cells but exclusively contained the more primitive progenitor cells, the BFU-megakaryocyte, high proliferative potential-colony-forming cell, and long-term bone marrow culture-initiating cell. The overall progenitor cell cloning efficiency of this subpopulation was greater than 7%. Both the CD34+ HLA-DR- and CD34+ HLA-DR+ cell subpopulations lacking KR expression contained few assayable hematopoietic progenitor cells. Long-term bone marrow cultures initiated with CD34+ HLA-DR- SR-1+ but not CD34+ HLA-DR- SR-1- cells, which were repeatedly supplemented with c-kit ligand (KL) and interleukin-3, generated assayable progenitor cells of at least 2 lineages for 10 weeks. These experiments demonstrate the expression of the KR throughout the

  12. Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer : A feasibility study

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Beijnen, JH; Piersma, H; vanderGraaf, WTA; deVries, EGE; Boonstra, J.

    1997-01-01

    The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte

  13. Role of cytokines in sustaining long-term human megakaryocytopoiesis in vitro.

    Science.gov (United States)

    Briddell, R A; Brandt, J E; Leemhuis, T B; Hoffman, R

    1992-01-15

    An in vitro liquid suspension culture system was used to determine the role of cytokines in sustaining long-term human megakaryocytopoiesis. Bone marrow cells expressing CD34 but not HLA-DR (CD34+DR-) were used as the inoculum of cells to initiate long-term bone marrow cultures (LTBMC). CD34+DR- cells (5 x 10(3)/mL) initially contained 0.0 +/- 0.0 assayable colony-forming unit-megakaryocytes (CFU-MK), 6.2 +/- 0.4 assayable burst-forming unit-megakaryocytes (BFU-MK), and 0.0 +/- 0.0 megakaryocytes (MK). LTBMCs were recharged every 48 hours with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-3, and/or IL-6, alone or in combination. LTBMCs were demidepopulated weekly or biweekly, the number of cells and MK enumerated, and then assayed for CFU-MK and BFU-MK. LTBMCs receiving no cytokine(s) contained no assayable CFU-MK or BFU-MK and no observable MK. LTBMCs receiving GM-CSF, IL-1 alpha, and/or IL-3 contained assayable CFU-MK and MK but no BFU-MK for 10 weeks of culture. The effects of GM-CSF and IL-3, IL-1 alpha and IL-3, but not GM-CSF and IL-1 alpha were additive with regards to their ability to augment the numbers of assayable CFU-MK during LTBMC. LTBMCs supplemented with IL-6 contained modest numbers of assayable CFU-MK for only 4 weeks; this effect was not additive to that of GM-CSF, IL-1 alpha, or IL-3. The addition of GM-CSF, IL-1 alpha, and IL-3 alone or in combination each led to the appearance of significant numbers of MKs during LTBMC. By contrast, IL-6 supplemented cultures contained relatively few MK. These studies suggest that CD34+DR- cells are capable of initiating long-term megakaryocytopoiesis in vitro and that a hierarchy of cytokines exists capable of sustaining this process.

  14. Recombinant human granulocyte colony-stimulating factor increases circulating CD34-postive cells in patients with AIDS

    DEFF Research Database (Denmark)

    Nielsen, S D; Dam-Larsen, S; Nielsen, C

    1997-01-01

    .e., the circulating hematopoietic progenitor cells (CD34 cells) in patients with AIDS, using the recombinant human granulocyte colony-stimulating factor (G-CSF). Eight patients with AIDS were treated with G-CSF for neutropenia (... G-CSF for 3-5 consecutive days. Within 5 days of initiation of G-CSF therapy, an increase in the absolute neutrophil count (ANC) was seen in all patients. There was a median increase in ANC from 0.4 to 3.4 x 10(9)/l. In addition, G-CSF treatment significantly increased the absolute number of CD34...... cells. The median increase in CD34 cells was from 0.8 to 2.2 x 10(6)/l. Finally, using a highly sensitive HIV-1 RNA PCR, we found that treatment of AIDS patients with G-CSF did not lead to enhanced HIV replication. These observations indicate that G-CSF may be used to mobilize CD34 cells in patients...

  15. Phenotypic features of first-generation transgenic goats for human granulocyte-colony stimulation factor production in milk.

    Science.gov (United States)

    Batista, Ribrio I T P; Melo, Carlos H S; Souza-Fabjan, Joanna M G; Teixeira, Dárcio I A; Melo, Luciana M; Freitas, Vicente J F

    2014-11-01

    Human granulocyte-colony stimulating factor (hG-CSF) is a hematopoietic growth factor used in neutropenic patients. It is produced in transgenic bacteria or cultured mammalian cells. As an alternative, we now show that hG-CSF can be expressed in the mammary gland of first-generation (F1) transgenic goats during induced lactation. Despite lower milk production, transgenic females presented a similar milk composition (fat, protein and lactose) when compared to non-transgenic (p > 0.05) ones. The mean concentration (±SD) of recombinant hG-CSF in milk during lactation was 360 ± 178 µg ml(-1). All clinical parameters, as well as kidney and liver function, indicated that F1 transgenic goats were healthy. Additionally, no ectopic hG-CSF expression was detected in studied tissues of F1 transgenic males. Thus, F1 hG-CSF-transgenic goats can express the recombinant protein in milk at quantities compatible with their use as bioreactors in a commercial-scale protein-production program.

  16. Zn(II released from zinc oxide nano/micro particles suppresses vasculogenesis in human endothelial colony-forming cells

    Directory of Open Access Journals (Sweden)

    Saeko Tada-Oikawa

    2015-01-01

    Full Text Available Zinc oxide (ZnO nanoparticles have been widely used in industry, cosmetics, and biomedicine. Recent studies suggested that these nanoparticles could have a major impact on the cardiovascular system. Endothelial progenitor cells (EPCs contribute to postnatal endothelial repair and regeneration. The present study dissected the effects of ZnO nanoparticles on vasculogenesis using human endothelial colony forming cells (ECFCs, which participate in post-natal vasculogenesis. Two types of ZnO particles were used (nano and micro, in addition to zinc chloride solutions with zinc ion concentrations equal to those in ZnO nanoparticles. Twenty-four-hour exposure induced cytotoxicity in a dose-dependent manner and increased ECFCs apoptosis in all groups. The exposure also reduced the functional capacity of ECFCs on Matrix gel to form tubules, compared with the control cells. These effects were associated with downregulation of expression of vascular endothelial growth factor receptor, VEGFR2 and CXC chemokine receptor, CXCR4. The results suggest that ZnO nanoparticles suppress vasculogenesis from ECFCs through downregulation of the expression of receptors related to vasculogenesis. These effects are based the concentration of released Zn(II.

  17. Analytical characterization of in vitro refolding in the quality by design paradigm: Refolding of recombinant human granulocyte colony stimulating factor.

    Science.gov (United States)

    Pathak, Mili; Dixit, Shruti; Muthukumar, S; Rathore, Anurag S

    2016-07-15

    Protein based therapeutics dominate most pharmaceutical pipelines today. For a therapeutic product to be effective, it is important that it is in its native form as slight modifications have been known to result in significantly different performance in the clinic. When expressed in hosts such as Escherichia coli, formation of inactive insoluble aggregates of proteins popularly known as inclusion bodies occurs in most cases. This necessitates the need for in vitro refolding to generate the native (and active) form of the therapeutic protein. This paper aims to provide an approach to generate a deeper understanding of refolding of a therapeutic protein and then to use it for its optimal production commercially. Recombinant human granulocyte colony stimulating factor has been chosen as the model protein. Seven orthogonal analytical tools have been used to elucidate the refolding process. By strategically using these tools protein refolding has been segregated into a series of well-defined sequence of events, starting from the unfolded random coil and ending with the uniquely folded metastable state. The study also suggests the choice of tools that can be used to monitor each event. We believe that this paper successfully demonstrates an approach to generate deeper understanding of the protein refolding process as per the expectations laid out in the Quality by Design paradigm. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Simplified in vitro refolding and purification of recombinant human granulocyte colony stimulating factor using protein folding cation exchange chromatography.

    Science.gov (United States)

    Vemula, Sandeep; Dedaniya, Akshay; Thunuguntla, Rahul; Mallu, Maheswara Reddy; Parupudi, Pavani; Ronda, Srinivasa Reddy

    2015-01-30

    Protein folding-strong cation exchange chromatography (PF-SCX) has been employed for efficient refolding with simultaneous purification of recombinant human granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of renatured and purified rhG-CSF, various chromatographic conditions, including the mobile phase composition and pH was evaluated. Additionally, the effects of additives such as urea, amino acids, polyols, sugars, oxidizing agents and their amalgamations were also investigated. Under the optimal conditions, rhG-CSF was efficaciously solubilized, refolded and simultaneously purified by SCX in a single step. The experimental results using ribose (2.0M) and arginine (0.6M) combination were found to be satisfactory with mass yield, purity and specific activity of 71%, ≥99% and 2.6×10(8)IU/mg respectively. Through this investigation, we concluded that the SCX refolding method was more efficient than conventional methods which has immense potential for the large-scale production of purified rhG-CSF. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Electronegative L5-LDL induces the production of G-CSF and GM-CSF in human macrophages through LOX-1 involving NF-κB and ERK2 activation.

    Science.gov (United States)

    Yang, Tzu-Ching; Chang, Po-Yuan; Kuo, Tzu-Ling; Lu, Shao-Chun

    2017-12-01

    Circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are associated with the severity of acute myocardial infarction (AMI). However, what causes increases in G-CSF and GM-CSF is unclear. In this study, we investigated whether L5-low-density lipoprotein (LDL), a mildly oxidized LDL from AMI, can induce G-CSF and GM-CSF production in human macrophages. L1-LDL and L5-LDL were isolated through anion-exchange chromatography from AMI plasma. Human macrophages derived from THP-1 and peripheral blood mononuclear cells were treated with L1-LDL, L5-LDL, or copper-oxidized LDL (Cu-oxLDL) and G-CSF and GM-CSF protein levels in the medium were determined. In addition, the effects of L5-LDL on G-CSF and GM-CSF production were tested in lectin-type oxidized LDL receptor-1 (LOX-1), CD36, extracellular signal-regulated kinase (ERK) 1, and ERK2 knockdown THP-1 macrophages. L5-LDL but not L1-LDL or Cu-oxLDL significantly induced production of G-CSF and GM-CSF in macrophages. In vitro oxidation of L1-LDL and L5-LDL altered their ability to induce G-CSF and GM-CSF, suggesting that the degree of oxidation is critical for the effects. Knockdown and antibody neutralization experiments suggested that the effects were caused by LOX-1. In addition, nuclear factor (NF)-κB and ERK1/2 inhibition resulted in marked reductions of L5-LDL-induced G-CSF and GM-CSF production. Moreover, knockdown of ERK2, but not ERK1, hindered L5-LDL-induced G-CSF and GM-CSF production. The results indicate that L5-LDL, a naturally occurring mild oxidized LDL, induced G-CSF and GM-CSF production in human macrophages through LOX-1, ERK2, and NF-κB dependent pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Research and Development Strategies for the Current and Future Medical Treatment of Radiation Casualties

    Science.gov (United States)

    2014-09-01

    human granulocyte-macrophage colony stimulating factor (GM-CSF) produced in Saccharomyces cerevisiae (S. cerevisiae ). It is similar to filgrastim in...cell REMM Radiation Emergency Medical Management rHuIL-12 recombinant human interleukin-12 S. cerevisiae Saccharomyces cerevisiae sBLA supplemental...treatment of supportive care and leukocyte growth factors mitigate the hematopoietic (HP) ARS that occurs at lower levels of radiation exposure. Therefore

  1. Antitumor activity of MGI 114 (6-hydroxymethylacylfulvene, HMAF), a semisynthetic derivative of illudin S, against adult and pediatric human tumor colony-forming units.

    Science.gov (United States)

    Hidalgo, M; Izbicka, E; Eckhardt, S G; MacDonald, J R; Cerna, C; Gomez, L; Rowinsky, E K; Weitman, S D; Von Hoff, D D

    1999-10-01

    MGI 114 (6-hydroxymethylacylfulvene, HMAF) is a novel semisynthetic antitumor compound derived from the sesquiterpene mushroom toxin illudin S. Although illudins did not demonstrate significant activity as antiproliferative agents in tumor-bearing animals, several properties including its potent inhibition of DNA synthesis and a unique interaction with DNA led to a structure-activity-based synthetic effort to obtain analogs with improved therapeutic potential. MGI 114 was selected for further development based on its antitumor activity in numerous preclinical tests. MGI 114 was evaluated against adult and pediatric human tumors taken directly from cancer patients and cultured in a human tumor colony-forming assay (HTCFA) to assess the antitumor spectra, concentration-response relationship, schedule dependence and activity of this agent against tumors considered resistant to conventional anticancer drugs. Human tumor colony-forming units were treated with HMAF at concentrations of 0.001, 0.01, 0.1 and 1 microg/ml, both as a 1 h exposure and as a continuous 14 day exposure. A response was scored if there was 50% or less colony survival. In vitro response rates in the range of 50-80% were observed against tumor colony-forming units originating from carcinomas of the colon, kidney, breast, lung cancer, ovary and melanoma. MGI 114 also demonstrated antitumor activity against neuroblastoma colony-forming units. Antitumor activity was not influenced by exposure time as demonstrated by the similar responses rates obtained with the 1 h and continuous exposure at all concentrations tested. However, there was a significant positive concentration-response relationship to both exposure duration with responses increasing from below 10% at the lowest concentration to over 70% at the highest concentration, except for the pediatric tumors on the 1 h exposure for which this relationship was less apparent. At the higher concentration tested, MGI 114 displayed substantial

  2. Mycobacterium massiliense Type II genotype leads to higher level of colony forming units and TNF-α secretion from human monocytes than Type I genotype.

    Science.gov (United States)

    Kim, Byoung-Jun; Shim, Tae Sun; Yi, Su-Yeon; Kim, Ho-Cheol; Kim, Bo-Ram; Lee, So-Young; Kook, Yoon-Hoh; Kim, Bum-Joon

    2015-10-01

    Recently, we introduced a novel Mycobacterium massiliense Type II genotype from Korean patients, in which all isolates showed only a rough (R) colony morphotype. In this study, we sought to compare clinical factors and virulence potentials of two genotypes of M. massiliense, Type I and Type II. Patients infected with Type II tend to be younger at infection than those infected with Type I (56.7 vs 62.3, p = 0.051). Type II was more significantly related to R colony type than Type I (34.1% vs 94.1%, p < 0.001). The Type II strain showed significantly more colony forming units (CFUs) and higher levels of TNF-α secretion in infection of human monocytes than the Type I strain. The challenge of extracted glycopeptidolipid (GPL) into human monocytes indicated that the loss of GPL from the cell wall of the Type II genotype led to a higher level of TNF-α secretion in a toll-like receptor 2(TLR2)-dependent manner. Taken together, our data suggest that the M. massiliense Type II genotype shows higher virulence than Type I, which may be due to the induction of TNF-α via the loss of GPL from the Type II cell wall. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  3. In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

    Science.gov (United States)

    Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

    2013-11-01

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

  4. Subcutaneous administration of interleukin-2 triggers Fcgamma receptor I expression on human peripheral blood neutrophils in solid and hematologic malignancies.

    Science.gov (United States)

    Sconocchia, G; Cococcetta, N Y; Campagnano, L; Amadori, S; Iorio, B; Boffo, V; Ferdinandi, V; Del Principe, I; Adorno, D; Casciani, C U

    2001-01-01

    Freshly isolated human polymorphonuclear cells (PMNCs) constitutively express Fcgamma receptor (Fc-gammaR) II and FcgammaRIII on the cell surface but not FcgammaRI. Cytokines such as interferon-gamma (IFNgamma), granulocyte-macrophage colony-stimulating factor (CSF), and granulocyte-CSF trigger FcgammaRI expression on (PMNCs). Because PMNCs express interleukin (IL)-2 receptor, we investigated whether IL-2 can induce FcgammaRI expression on PMNCs isolated from IL-2-treated metastatic renal cell carcinoma (MRCC) and low-grade non-Hodgkin lymphoma (LGNHL) patients. Pretherapy flow cytometry analysis of Fcgamma receptors on PMNCs did not show FcgammaRI expression. Interestingly, 3 days after therapy, PMNCs displayed a detectable amount of FcgammaRI on the cell surface. Kinetic studies on the in vivo effects of IL-2 on MRCC patients showed that FcgammaRI was transiently expressed, starting within 3-6 days of therapy, remaining expressed for 10-15 days, and rapidly declining, whereas such expression remained stable for months in LGNHL patients. In contrast, Fc-gammaRII was not affected. In addition, FcgammaRI+ PMNCs coated in vitro with a bispecific antibody Fab anti-FcgammaRI x anti-HER-2/neu formed intercellular conjugates with a human HER-2/neu-transfected 3T3 cell line (HER-2/neu-3T3). Interleukin-2 treatment increased the number of FcgammaRIII low eosinophils, leading to a change in FcgammaRIII distribution among granulocyte cell subsets. In vitro IL-2 treatment of purified PMNCs failed to generate Fc-gammaRI expression, suggesting that IL-2 indirectly causes FcgammaRI expression. During the IL-2 administration, we did not observe significant changes in IFNgamma serum level. In conclusion, our observation may be used to potentiate the antitumor effects of IL-2 in novel immunotherapy regimens, perhaps by redirecting FcgammaRI+ PMNCs against cancer cells by heteroconjugate antibodies and monitoring the biologic activity of subcutaneous IL-2 in cancer patients.

  5. In vitro expansion of Lin{sup +} and Lin{sup −} mononuclear cells from human peripheral blood

    Energy Technology Data Exchange (ETDEWEB)

    Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul [School of Bioscience and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Selangor (Malaysia); Rohaya, M. A. W. [Department of Orthodontics, Faculty of Dentistry, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur (Malaysia)

    2013-11-27

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin{sup −}) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin{sup +}) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin{sup −} cell population. The ability of Lin{sup +} and Lin{sup −} to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin{sup +} and Lin{sup −} were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin{sup +} mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin{sup −} stem cells were not able to survive in proliferation medium however

  6. Effects of interferon-γ and granulocyte colony-stimulating factor on antifungal activity of human polymorphonuclear neutrophils against Candida albicans grown as biofilms or planktonic cells.

    Science.gov (United States)

    Katragkou, Alphaspasia; Simitsopoulou, Maria; Chatzimoschou, Athanasios; Georgiadou, Elpiniki; Walsh, Thomas J; Roilides, Emmanuel

    2011-09-01

    Candida albicans is a leading cause of biofilm-related infections. As Candida biofilms are recalcitrant to host defenses, we sought to determine the effects of interferon-γ and granulocyte colony-stimulating factor, two pro-inflammatory cytokines, on the antifungal activities of human polymorphonuclear neutrophils (PMNs) against C. albicans biofilms, using an in vitro biofilm model. Priming of PMNs by these cytokines augmented fungal damage of planktonic cells; however, priming of PMNs did not have the same effect against Candida biofilms. Biofilm phenotype appears to play an important role in protecting C. albicans from the innate immune system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis

    DEFF Research Database (Denmark)

    Nielsen, H

    1993-01-01

    After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease...... of neutrophil granulocytes (including immature forms) of 33.108 x 10(9) l-1 on day 12 after admission. The patient only had minor infectious complications during the neutropenic period. In conclusion, early treatment with filgrastim seems warranted in severe cases of clozapine-induced agranulocytosis. A dosage...

  8. Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura?

    Directory of Open Access Journals (Sweden)

    Every Alison L

    2011-02-01

    Full Text Available Abstract Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura. The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season, concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

  9. Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura)?

    Science.gov (United States)

    2011-01-01

    Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura). The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season), concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials. PMID:21314909

  10. Combination of roflumilast with a beta-2 adrenergic receptor agonist inhibits proinflammatory and profibrotic mediator release from human lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Tannheimer Stacey L

    2012-03-01

    Full Text Available Abstract Background Small airway narrowing is an important pathology which impacts lung function in chronic obstructive pulmonary disease (COPD. The accumulation of fibroblasts and myofibroblasts contribute to inflammation, remodeling and fibrosis by production and release of mediators such as cytokines, profibrotic factors and extracellular matrix proteins. This study investigated the effects of the phosphodiesterase 4 inhibitor roflumilast, combined with the long acting β2 adrenergic agonist indacaterol, both approved therapeutics for COPD, on fibroblast functions that contribute to inflammation and airway fibrosis. Methods The effects of roflumilast and indacaterol treatment were characterized on transforming growth factor β1 (TGFβ1-treated normal human lung fibroblasts (NHLF. NHLF were evaluated for expression of the profibrotic mediators endothelin-1 (ET-1 and connective tissue growth factor (CTGF, expression of the myofibroblast marker alpha smooth muscle actin, and fibronectin (FN secretion. Tumor necrosis factor-α (TNF-α was used to induce secretion of chemokine C-X-C motif ligand 10 (CXCL10, chemokine C-C motif ligand 5 (CCL5 and granulocyte macrophage colony-stimulating factor (GM-CSF from NHLF and drug inhibition was assessed. Results Evaluation of roflumilast (1-10 μM showed no significant inhibition alone on TGFβ1-induced ET-1 and CTGF mRNA transcripts, ET-1 and FN protein production, alpha smooth muscle expression, or TNF-α-induced secretion of CXCL10, CCL5 and GM-CSF. A concentration-dependent inhibition of ET-1 and CTGF was shown with indacaterol treatment, and a submaximal concentration was chosen for combination studies. When indacaterol (0.1 nM was added to roflumilast, significant inhibition was seen on all inflammatory and fibrotic mediators evaluated, which was superior to the inhibition seen with either drug alone. Roflumilast plus indacaterol combination treatment resulted in significantly elevated phosphorylation

  11. Synthesis of human prolactin in Chinese hamster ovary (CHO) cells; Sintese de prolactina humana em celulas de ovario de hamster chines (CHO)

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Carlos Roberto Jorge

    2000-07-01

    Three different eukaryotic expression vectors, based on the same selectable gene marker (dhfr), have been used for dhf- CHO cells transfection to rapidly isolate stable cell lines capable of secreting high levels of recombinant human prolactin (rec-hPRL). Two vectors, one codifying a human prolactin (p658-hPRL) and the other a tag-prolactin (p658-tagPRL), contain the complete hepatitis B virus-X (HBV-X) gene coding for a viral transactivator and a sequence derived from the granulocyte-macrophage colony-stimulating factor (GM-CSF) that mediates selective dhfr mRNA degradation. These vectors have the advantage of rapidly obtaining stable cell lines without methotrexate amplification. The highest secretion obtained by these vectors was of approximately 10 {mu}g hPRU10{sup 6} cells/day. The other vector (pEDdc-hPRL) is based on a dicistronic expression system, containing an internal ribosome entry site isolated from the encephalomyocarditis (EMC) virus. This vector before amplification provided secretion levels at least 10 fold lower than that obtained with the other two vectors. However, after three steps of methotrexate amplification, it provided some clones able to secrete up to 30 {mu}g hPRU10{sup 6} cells/day. This is the first report describing the production and purification of rec-hPRL from CHO cells, obtaining secretion levels with both vectors higher than those reported so far for this hormone in other eukaryotic systems. CHO-derived rec-hPRL contained approximately 10 % of the glycosylated form, a value that is consistent with results reported for hPRL purified from the pituitary or from transformed murine C-127 cells. CHO-derived rec-hPRL was purified with good yield, obtaining also a good resolution between non-glycosylated and glycosylated prolactin. The latter, when its potency was determined via an in vitro bioassay, presented a 47 % lower bioactivity. A qualitative and quantitative analysis of these forms was also possible thanks to the setting up of a

  12. Pepsin-pancreatin protein hydrolysates from extruded amaranth inhibit markers of atherosclerosis in LPS-induced THP-1 macrophages-like human cells by reducing expression of proteins in LOX-1 signaling pathway

    Science.gov (United States)

    2014-01-01

    Background Atherosclerosis is considered a progressive disease that affects arteries that bring blood to the heart, to the brain and to the lower end. It derives from endothelial dysfunction and inflammation, which play an important role in the thrombotic complications of atherosclerosis. Cardiovascular disease is the leading cause of death around the world and one factor that can contribute to its progression and prevention is diet. Our previous study found that amaranth hydrolysates inhibited LPS-induced inflammation in human and mouse macrophages by preventing activation of NF-κB signaling. Furthermore, extrusion improved the anti-inflammatory effect of amaranth protein hydrolysates in both cell lines, probably attributed to the production of bioactive peptides during processing. Therefore, the objective of this study was to compare the anti-atherosclerotic potential of pepsin-pancreatin hydrolysates from unprocessed and extruded amaranth in THP-1 lipopolysaccharide-induced human macrophages and suggest the mechanism of action. Results Unprocessed amaranth hydrolysate (UAH) and extruded amaranth hydrolysate (EAH) showed a significant reduction in the expression of interleukin-4 (IL-4) (69% and 100%, respectively), interleukin-6 (IL-6) (64% and 52%, respectively), interleukin-22 (IL-22) (55% and 70%, respectively). Likewise, UAH and EAH showed a reduction in the expression of monocyte-chemo attractant protein-1 (MCP-1) (35% and 42%, respectively), transferrin receptor-1 (TfR-1) (48% and 61%, respectively), granulocyte-macrophage colony-stimulating factor (GM-CSF) (59% and 63%, respectively), and tumor necrosis factor-α (TNF-α) (60% and 63%, respectively). Also, EAH reduced the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) (27%), intracellular adhesion molecule-1 (ICAM-1) (28%) and matrix metalloproteinase-9 (MMP-9) (19%), important molecular markers in the atherosclerosis pathway. EAH, led to a reduction of 58, 52 and 79% for

  13. The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel.

    Science.gov (United States)

    Guerreiro, Patrícia S; Corvacho, Eduardo; Costa, João G; Saraiva, Nuno; Fernandes, Ana S; Castro, Matilde; Miranda, Joana P; Oliveira, Nuno G

    2017-10-01

    The human apurinic/apyrimidinic endonuclease 1 (APE1) is an ubiquitous multifunctional DNA repair enzyme and a redox signalling protein. Our work addressed the inhibition of APE1 redox function using E3330, as single agent or in combination with docetaxel (DTX), in human breast cancer MDA-MB-231 cells. E3330 decreased the colony formation of DTX-treated cells. In addition, E3330 alone significantly reduced the collective cell migration as assessed by the wound-healing assay, whereas the combined treatment decreased chemoinvasion. These results suggest that the inhibition of APE1 redox function might have therapeutic potential by modulating cell migration and invasion in metastatic breast cancer. © 2017 John Wiley & Sons A/S.

  14. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  15. Evaluation of a biosimilar granulocyte colony-stimulating factor (filgrastim XM02 for peripheral blood stem cell mobilization and transplantation: a single center experience in Japan

    Directory of Open Access Journals (Sweden)

    Yoshimura H

    2017-01-01

    Full Text Available Hideaki Yoshimura, Masaaki Hotta, Takahisa Nakanishi, Shinya Fujita, Aya Nakaya, Atsushi Satake, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, Japan Background: Biosimilar granulocyte colony-stimulating factor (G-CSF has recently been introduced into clinical practice. G-CSFs are used to mobilize CD34+ cells and accelerate engraftment after transplantation. However, in Asia, particularly in Japan, data for peripheral blood stem cell (PBSC mobilization by this biosimilar G-CSF are currently lacking. Therefore, the clinical efficacy and safety of biosimilar G-CSF for hematopoietic stem cell transplantation needs to be evaluated in a Japanese context.Materials and methods: The subjects included two groups of patients with malignant lymphoma and multiple myeloma. All patients received chemotherapy priming for the mobilization of PBSCs. All patients were treated with chemotherapy followed by the administration of either the biosimilar G-CSF, filgrastim XM02 (FBNK, or the originators, filgrastim, or lenograstim.Results: There were no significant differences among FBNK, filgrastim, and lenograstim treatments in the numbers of CD34+ cells in harvested PBSCs, the scores for granulocyte/macrophage colony forming units, or for malignant lymphoma and multiple myeloma patients evaluated as separate or combined cohorts. In addition, there were no significant differences in safety, side effects, complications, or the time to engraftment after autologous hematopoietic stem cell transplantation.Conclusion: Biosimilar FBNK shows the same efficacy and safety as originator G-CSFs for facilitating bone marrow recovery in Japanese malignant lymphoma and multiple myeloma patients undergoing stem cell transplantation. In addition, it is less expensive than the originators, reducing hospitalization costs. Keywords: G-CSF, biosimilar, peripheral blood stem cell, hematological

  16. Effects of Benzo(epyrene on reactive oxygen/nitrogen species and inflammatory cytokines induction in human RPE cells and attenuation by mitochondrial-involved mechanism

    Directory of Open Access Journals (Sweden)

    M Fernanda Estrago-Franco

    2016-01-01

    Full Text Available Purpose: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS, complement and inflammatory cytokine levels induced by Benzo(epyrene [B(ep], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19 in vitro. Methods: ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(ep or DMSO (dimethyl sulfoxide-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III and ROS/RNS levels were measured with a fluorescent H 2 DCFDA assay. Multiplex bead arrays were used to measure levels of Interleukin-6 (IL-6, Interleukin-8 (IL-8, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, Transforming Growth Factor alpha (TGF-α and Vascular Endothelial Growth Factor (VEGF. IL-6 levels were also measured by an enzyme-linked immunosorbent assay. Real-time qPCR analyses were performed with primers for C3 (component 3, CFH (inhibits complement activation, CD59 (inhibitor of the complement membrane attack complex (MAC and CD55/DAF (accelerates decay of target complement target proteins. Results: The ARPE-19 cultures treated with B(ep showed significantly increased ROS/RNS levels (P < 0.001, which were then partially reversed by 6 μM Antimycin A (19%, P = 0.03, but not affected by the other ROS/RNS inhibitors. The B(ep treated cultures demonstrated increased levels of IL-6 (33%; P = 0.016 and GM-CSF (29%; P = 0.0001 compared to DMSO-equivalent controls, while the expression levels for components of the complement pathway (C3, CFH, CD59 and CD55/DAF were not changed. Conclusion: The cytotoxic effects of B(ep include elevated ROS/RNS levels along with pro-inflammatory IL-6 and GM-CSF proteins. Blocking the Qi site of cytochrome c reductase (complex III with Antimycin A led to

  17. Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human melanoma in vitro model: studying immunogenic cell death, dendritic cell maturation and interaction with cytotoxic T lymphocytes

    Directory of Open Access Journals (Sweden)

    Heinrich B

    2017-05-01

    Full Text Available B Heinrich,1 J Klein,1 M Delic,1 K Goepfert,1 V Engel,1 L Geberzahn,1 M Lusky,2 P Erbs,2 X Preville,3 M Moehler1 1First Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany; 2Transgene SA, Illkirch-Graffenstaden, 3Amoneta Diagnostics, Huningue, France Abstract: Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF or transforming 5-fluorocytosine (5-FC into 5-fluorouracil (5-FU. We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on human immune cells, specifically regarding the activation of dendritic cells (DCs and the interaction with the autologous cytotoxic T lymphocyte (CTL clone, was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone or in combination with 5-FC and 5-FU. The influence of viral infection on cell viability followed a time- and multiplicity of infection dependent manner. Combination of virus treatment with 5-FU resulted in stronger reduction of cell viability. TG6002 in combination with 5-FC did not significantly strengthen the reduction of cell viability in this setting. Expression of calreticulin and high mobility group 1 protein (HMGB1, markers of immunogenic cell death (ICD, could be detected after viral infection. Accordingly, DC maturation was noted after viral oncolysis. DCs presented stronger expression of activation and maturation markers. The autologous CTL clone IVSB expressed the activation marker CD69, but viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia viruses JX-GFP and TG6002 lyse

  18. Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing.

    Science.gov (United States)

    Cunyat, Francesc; Rainho, Jennifer N; West, Brian; Swainson, Louise; McCune, Joseph M; Stevenson, Mario

    2016-07-15

    Strategies aimed at eliminating persistent viral reservoirs from HIV-1-infected individuals have focused on CD4(+) T-cell reservoirs. However, very little attention has been given to approaches that could promote elimination of tissue macrophage reservoirs. HIV-1 infection of macrophages induces phosphorylation of colony-stimulating factor 1 receptor (CSF-1R), which confers resistance to apoptotic pathways driven by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thereby promoting viral persistence. In this study, we assessed whether CSF-1R antagonists (PLX647, PLX3397, and PLX5622) restored apoptotic sensitivity of HIV-1-infected macrophages in vitro PLX647, PLX3397, and PLX5622 at clinically relevant concentrations blocked the activation of CSF-1R and reduced the viability of infected macrophages, as well as the extent of viral replication. Our data show that strategies targeting monocyte colony-stimulating factor (MCSF) signaling could be used to promote elimination of HIV-1-infected myeloid cells and to contribute to the elimination of persistent viral reservoirs. As the HIV/AIDS research field explores approaches to eliminate HIV-1 in individuals on suppressive antiviral therapy, those approaches will need to eliminate both CD4(+) T-cell and myeloid cell reservoirs. Most of the attention has focused on CD4(+) T-cell reservoirs, and scant attention has been paid to myeloid cell reservoirs. The distinct nature of the infection in myeloid cells versus CD4(+) T cells will likely dictate different approaches in order to achieve their elimination. For CD4(+) T cells, most strategies focus on promoting virus reactivation to promote immune-mediated clearance and/or elimination by viral cytopathicity. Macrophages resist viral cytopathic effects and CD8(+) T-cell killing. Therefore, we have explored clearance strategies that render macrophages sensitive to viral cytopathicity. This research helps inform the design of strategies to promote

  19. Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates.

    Science.gov (United States)

    Andrews, R G; Briddell, R A; Knitter, G H; Rowley, S D; Appelbaum, F R; McNiece, I K

    1995-01-01

    We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG-CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of

  20. EFFECTIVENESS AND SAFETY OF RECOMBINANT HUMAN GRANULOCYTIC COLONY-STIMULATING FACTOR IN TREATMENT OF GRANULOCYTOPENIA DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2010-01-01

    Full Text Available Treatment of patients with severe clinical course of juvenile rheumatoid arthritis (JRA is difficult problem. During the last years genetically engineered biological drugs are used equally with traditional immunosuppressive agents in treatment of severe forms of juvenile arthritis. High effectiveness of these drugs can be accompanied with development of unfavorable effects, for example, febrile neutropenia. The article presents results of a study of effectiveness and safety of recombinant human granulocytic colony-stimulating factor — filgrastim (Leucostim — in treatment of granulocytopenia developed during immunosuppressive therapy in 16 patients with JRA. It was shown that administration of filgrastim arrests leucopenia in 100% of patients and granulocytopenia — in 93% of patients in 24 hours after first injection. High effectiveness of drug was combined with good tolerability and safety.Key words: children, treatment, granulocytopenia, filgrastim, juvenile rheumatoid arthritis.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:94-100

  1. In vitro effects on proliferation, apoptosis and colony inhibition in ER-dependent and ER-independent human breast cancer cells by selected mushroom species.

    Science.gov (United States)

    Gu, Yu-Huan; Leonard, Jessica

    2006-02-01

    Breast cancer is the most commonly diagnosed cancer among women in Western countries. Currently, there is no effective therapy for malignant estrogen-independent breast cancer. We have screened 38 species of edible mushroom on human estrogen-receptor positive (MCF-7) and estrogen-receptor negative (MDA-MB-231, BT-20) breast cancer cells to select potential agents with broad-spectrum antitumor activity against breast cancer cells. Water-based extracts of three mushroom species, Coprinellus sp., Coprinus comatus, Flammulina velutipes (CME, CCE and FVE, respectively), were identified as novel anti-breast cancer agents. The anti-tumor activities include: 1) marked growth inhibition of both ER+ and ER- breast cancer cells; 2) induction of rapid apoptosis on both ER+ and ER- cells; 3) significant inhibition of MCF-7 tumor colony formation in vitro. The antiproliferative and cytotoxic activities of the three mushroom extracts were dose-dependent, regardless of the hormone receptor status of the cancer cells. The degree of produced cytotoxicity on ER- breast cancer cells was very high, while the IC50 of mushroom extract CME was found to be as low as 40 microg/ml on MDA-MB-231 cells and the IC50 of mushroom extract FVE was only 30 microg/ml on BT-20 cells. More interestingly, mushroom extracts CME and FVE induced an exceptionally rapid apoptosis on MCF-7 and MDA-MB-231 detected by Annexin V-FITC within 2 h of treatment and DNA fragment end-labeling assay (TUNEL) in 5 h of treatment. Anchorage-independent growth assays indicated that the MCF-7 tumor colony formation rate was reduced by 60% in CCE- and CME-treated cells and nearly completely inhibited (99%) by FVE treatment. These results suggest that mushroom species Coprinus comatus, Coprinellus sp. and Flammulina velutipes contain potent antitumor compounds for breast cancer. Our finding is important due to the lack of chemotherapeutic and chemopreventive agents for ER- human breast cancer.

  2. On colonial grounds

    NARCIS (Netherlands)

    Dommelen, Peter Alexander René van

    1998-01-01

    As a study of the colonial situations of first millennium BC Sardinia, this book is as much an investigation into colonialism as a sociological category, as it explores the specific historical conditions of a particular region. Taking a fresh look at colonialism in Mediterranean archaeology from a

  3. Tinospora cordifolia induces colony stimulating activity in serum.

    Directory of Open Access Journals (Sweden)

    Thatte U

    1994-10-01

    Full Text Available Tinospora cordifolia (Tc is an Indian medicinal plant with proven immunomodulatory activity. This study was performed to elucidate its possible mechanism of action. We measured CFU-GM Cotony forming units of the granulocyte-macrophage series in serum of mice treated with Tc. We found that 10 days treatment with Tc (100 mg/ kg/d induced a significant (p < 0.01 increase in the number of CFU-GM (255 +/- 49.32 vs 38.51 +/- 9.98 This suggests that activation of macrophages by Tc leads to increase in GM-CSF which leads to leucocytosis and improved neutrophil function.

  4. High pH solubilization and chromatography-based renaturation and purification of recombinant human granulocyte colony-stimulating factor from inclusion bodies.

    Science.gov (United States)

    Li, Ming; Fan, Hua; Liu, Jiahua; Wang, Minhong; Wang, Lili; Wang, Chaozhan

    2012-03-01

    Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a very efficient therapeutic protein drug which has been widely used in human clinics to treat cancer patients suffering from chemotherapy-induced neutropenia. In this study, rhG-CSF was solubilized from inclusion bodies by using a high-pH solution containing low concentration of urea. It was found that solubilization of the rhG-CSF inclusion bodies greatly depended on the buffer pH employed; alkalic pH significantly favored the solubilization. In addition, when small amount of urea was added to the solution at high pH, the solubilization was further enhanced. After solubilization, the rhG-CSF was renatured with simultaneous purification by using weak anion exchange, strong anion exchange, and hydrophobic interaction chromatography, separately. The results indicated that the rhG-CSF solubilized by the high-pH solution containing low concentration of urea had much higher mass recovery than the one solubilized by 8 M urea when using anyone of the three refolding methods employed in this work. In the case of weak anion exchange chromatography, the high pH solubilized rhG-CSF could get a mass recovery of 73%. The strategy of combining solubilization of inclusion bodies at high pH with refolding of protein using liquid chromatography may become a routine method for protein production from inclusion bodies.

  5. Salmonella detection and aerobic colony count in deep-frozen carcasses of house sparrow (Passer domesticus and starling (Sturnus vulgaris intended for human consumption

    Directory of Open Access Journals (Sweden)

    Frédérique Pasquali

    2014-06-01

    Full Text Available Wild birds are potential vehicles of zoonotic pathogen transmission to humans. The zoonotic concern increases for small wild birds like house sparrows (Passer domesticus and starlings (Sturnus vulgaris which are hunted in developing countries and commercialised in Italy for human consumption. From June to October 2011, 330 house sparrows and 140 starlings were hunted and slaughtered. Deepfrozen carcasses were transported to Italy and stored for 6-8 months at -18°C. Aerobic colony count and Salmonella detection in carcasses were assessed following standard microbiological methods (ISO 4833:2003 and ISO 6579:2004, respectively. Carcasses of house sparrows showed higher levels of aerobic bacteria in comparison to starling carcasses (5.7 vs 3.2 log10 CFU/g. Moreover, 7 out of 11 lots of carcasses of house sparrows were positive for Salmonella. Among the 18 isolates of Salmonella, 14 were S. Typhimurium, 2 were S. Enteritidis, and 2 were not distinguishable. All of them were susceptible to antibiotics. All tested carcasses of starling were Salmonella negative. Deep-freezing was not efficient as a decontamination technique on carcasses of house sparrows.

  6. Military labour mobilisation in colonial Lesotho during World War II ...

    African Journals Online (AJOL)

    In 1940, Great Britain's wartime exploitation of the human and material resources of its colonial empire was extended to colonial Lesotho (then known as Basutoland). The aim of this article, therefore, is to trace the four-year military labour mobilisation process in that colony, with special attention to the timing, number and ...

  7. Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro.

    Science.gov (United States)

    Malashchenko, Vladimir Vladimirovich; Meniailo, Maxsim Evgenievich; Shmarov, Viacheslav Anatolievich; Gazatova, Natalia Dinislamovna; Melashchenko, Olga Borisovna; Goncharov, Andrei Gennadievich; Seledtsova, Galina Victorovna; Seledtsov, Victor Ivanovich

    2018-03-01

    We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3 + T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA + /CD197 + naive T cells, CD45RA - /CD197 + central memory T cells, CD45RA - /CD197 - effector memory T cells and CD45RA + /CD197 - terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114 + T cells in central memory CD4 + T cell compartment. A dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38 + T cells in CD4 + naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4 - central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

    Science.gov (United States)

    Doloff, Joshua C.; Veiseh, Omid; Vegas, Arturo J.; Tam, Hok Hei; Farah, Shady; Ma, Minglin; Li, Jie; Bader, Andrew; Chiu, Alan; Sadraei, Atieh; Aresta-Dasilva, Stephanie; Griffin, Marissa; Jhunjhunwala, Siddharth; Webber, Matthew; Siebert, Sean; Tang, Katherine; Chen, Michael; Langan, Erin; Dholokia, Nimit; Thakrar, Raj; Qi, Meirigeng; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2017-06-01

    Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

  9. Administration of recombinant human granulocyte-colony-stimulating factor does not induce long-lasting detectable epigenetic alterations in healthy donors.

    Science.gov (United States)

    Leitner, Gerda C; Faschingbauer, Martin; Wenda, Sabine; Weigel, Günter; Fischer, Gottfried

    2014-12-01

    The short-term safety profile of recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) in the allogeneic stem cell setting seems acceptable; only few data on long-term safety are available. To further study possible epigenetic alterations, we investigated prospectively the influence of rHuG-CSF on DNA methyltransferase (DNMT) activity and on changes in DNA methylation of candidate genes in peripheral blood cells of healthy unrelated stem cell donors within an observation period of 1 year. In this study, 20 stem cell donors (14 male/six female; median age, 40 years; range, 22-54 years) and 20 sex- and age-matched blood component donors (controls) were included. Sampling was performed before rHuG-CSF administration; at the time of donation; and on Days (+1), 7, 30, 100, 180, and 360 in both groups. Analysis of DNMT activity in nuclear extracts was performed using a modified radionuclide assay. We performed methylation-specific polymerase chain reaction to detect the methylation status of promoter CpG islands of the genes of the retinoic acid receptor beta (RAR-B) and the Ras association domain family 1A (RASSF1A). DNMT activity increased significantly on the day of donation and 1 day after (p healthy stem cell donors. © 2014 AABB.

  10. Study by X-ray diffraction and Infrared spectroscopy of human bones of the pre hispanic and colonial epoch; Estudio por Difraccion de rayos X y Espectroscopia infrarroja de huesos humanos de la epoca prehispanica y colonial

    Energy Technology Data Exchange (ETDEWEB)

    Canto, A.B.; Quintana, P.; Alvarado G, J. [Cinvestav-Unidad Merida, Carretera Antigua a Progreso km. 6, Apdo. Postal 73 Cordemex, 97310 Merida, Yucatan (Mexico); Tiesler, V. [Facultad de Ciencias Antropologicas, UADY, 97000 Merida, Yucatan (Mexico); Diaz F, L.L. [Cinvestav-Unidad Queretaro, Libramiento Norponiente No. 2000, Fracc. Real de Juriquilla, 76230 Queretaro (Mexico)

    2004-07-01

    This paper explores the structure of bony remains obtained from different Pre hispanic and colonial Mayan burial contexts and sites. This study was conducted using X-ray diffraction and infrared spectroscopy in order to identify the phases and impurities present in the archaeological bones and to measure the degree of hydroxyapatite crystallinity. With it, we aim at examining the potential structural influence that different burial spaces (chamber as opposed to filled burial space), and soil properties (karstic soil, marshland and cenote) had on the bone samples. The sites were chosen from two different time periods: Pre hispanic (before 1519 d.C.) and Colonial (after 1519 d.C.). Some samples were collected from Siho, Mayapan y Oxkintok in the Puuc area. Other come from Calakmul, in Campeche's southeast, from Xcambo on the north coast of the Peninsula, and from the city of Campeche. Additional remains were recovered from the site of Palenque, Chiapas, where the soil contains higher contents of clay mineral than the karstic substrates that characterize the Peninsula of Yucatan. (Author) 40 refs., 4 tabs., 6 figs.

  11. Proliferation-stimulating effect of colony stimulating factor 2 on porcine trophectoderm cells is mediated by activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Wooyoung Jeong

    Full Text Available Colony-stimulating factor 2 (CSF2, also known as granulocyte macrophage colony-stimulating factor, facilitates mammalian embryonic development and implantation. However, biological functions and regulatory mechanisms of action of porcine endometrial CSF2 in peri-implantation events have not been elucidated. The aim of present study was to determine changes in cellular activities induced by CSFs and to access CSF2-induced intracellular signaling in porcine primary trophectoderm (pTr cells. Differences in expression of CSF2 mRNA in endometrium from cyclic and pregnant gilts were evaluated. Endometrial CSF2 mRNA expression increases during the peri-implantation period, Days 10 to 14 of pregnancy, as compared to the estrous cycle. pTr cells obtained in Day 12 of pregnancy were cultured in the presence or absence of CSF2 (20 ng/ml and LY294002 (20 µM, U0126 (20 µM, rapamycin (20 nM, and SB203580 (20 µM. CSF2 in pTr cell culture medium at 20 ng/ml significantly induced phosphorylation of AKT1, ERK1/2, MTOR, p70RSK and RPS6 protein, but not STAT3 protein. Also, the PI3K specific inhibitor (LY294002 abolished CSF2-induced increases in p-ERK1/2 and p-MTOR proteins, as well as CSF2-induced phosphorylation of AKT1. Changes in proliferation and migration of pTr cells in response to CSF2 were examined in dose- and time-response experiments. CSF2 significantly stimulated pTr cell proliferation and, U0126, rapamycin and LY294002 blocked this CSF2-induced proliferation of pTr cells. Collectively, during the peri-implantation phase of pregnancy in pigs, endometrial CSF2 stimulates proliferation of trophectoderm cells by activation of the PI3K-and ERK1/2 MAPK-dependent MTOR signal transduction cascades.

  12. First-in-Human Study of AMG 820, a Monoclonal Anti-Colony-Stimulating Factor 1 Receptor Antibody, in Patients with Advanced Solid Tumors.

    Science.gov (United States)

    Papadopoulos, Kyriakos P; Gluck, Larry; Martin, Lainie P; Olszanski, Anthony J; Tolcher, Anthony W; Ngarmchamnanrith, Gataree; Rasmussen, Erik; Amore, Benny M; Nagorsen, Dirk; Hill, John S; Stephenson, Joe

    2017-10-01

    Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0.5 mg/kg once weekly or 1.5 to 20 mg/kg every 2 weeks until disease progression, adverse event (AE), or consent withdrawal.Results: Twenty-five patients received ≥1 dose of AMG 820. AMG 820 was tolerated up to 20 mg/kg; the MTD was not reached. One dose-limiting toxicity was observed (20 mg/kg; nonreversible grade 3 deafness). Most patients (76%) had treatment-related AEs; the most common were periorbital edema (44%), increased aspartate aminotransferase (AST; 28%), fatigue (24%), nausea (16%), increased blood alkaline phosphatase (12%), and blurred vision (12%). No patients had serious or fatal treatment-related AEs; 28% had grade ≥3 treatment-related AEs. Grade 3 AST elevations resolved when treatment was withheld. AMG 820 showed linear pharmacokinetics, with minimal accumulation (AMG 820 was tolerated with manageable toxicities up to 20 mg/kg every 2 weeks. Pharmacodynamic response was demonstrated, and limited antitumor activity was observed. Clin Cancer Res; 23(19); 5703-10. ©2017 AACR. ©2017 American Association for Cancer Research.

  13. Hematopoietic growth factors for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Hansen, P B; Penkowa, M; Johnsen, H E

    1998-01-01

    of leukemic myelopoiesis and subsequent progression into overt acute myeloid leukemia. In conclusion, combinations of hematopoietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and unpredictable clinical outcome there is a need for extended laboratory research......Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or rh interleukin-3 (rhIL-3) effectively stimulate and expand marrow myelopoiesis resulting in a dose-dependent increment of peripheral blood...

  14. Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants

    National Research Council Canada - National Science Library

    Ali, Omar A; Verbeke, Catia; Johnson, Chris; Sands, R Warren; Lewin, Sarah A; White, Des; Doherty, Edward; Dranoff, Glenn; Mooney, David J

    2014-01-01

    ...) subsets and cytokines critical to this efficacy. Three-dimensional, porous polymer matrices loaded with tumor lysates and presenting distinct combinations of granulocyte macrophage colony-stimulating factor (GM-CSF...

  15. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

    National Research Council Canada - National Science Library

    Andtbacka, Robert H I; Kaufman, Howard L; Collichio, Frances; Amatruda, Thomas; Senzer, Neil; Chesney, Jason; Delman, Keith A; Spitler, Lynn E; Puzanov, Igor; Agarwala, Sanjiv S; Milhem, Mohammed; Cranmer, Lee; Curti, Brendan; Lewis, Karl; Ross, Merrick; Guthrie, Troy; Linette, Gerald P; Daniels, Gregory A; Harrington, Kevin; Middleton, Mark R; Miller, Jr, Wilson H; Zager, Jonathan S; Ye, Yining; Yao, Bin; Li, Ai; Doleman, Susan; VanderWalde, Ari; Gansert, Jennifer; Coffin, Robert S

    2015-01-01

    Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF...

  16. ColonyArea: an ImageJ plugin to automatically quantify colony formation in clonogenic assays.

    Directory of Open Access Journals (Sweden)

    Camilo Guzmán

    Full Text Available The clonogenic or colony formation assay is a widely used method to study the number and size of cancer cell colonies that remain after irradiation or cytotoxic agent administration and serves as a measure for the anti-proliferative effect of these treatments. Alternatively, this assay is used to quantitate the transforming potential of cancer associated genes and chemical agents. Therefore, there is a need for a simplified and standardized analysis of colony formation assays for both routine laboratory use and for parallelized automated analysis. Here we describe the freely available ImageJ-plugin "ColonyArea", which is optimized for rapid and quantitative analysis of focus formation assays conducted in 6- to 24-well dishes. ColonyArea processes image data of multi-well dishes, by separating, concentrically cropping and background correcting well images individually, before colony formation is quantitated. Instead of counting the number of colonies, ColonyArea determines the percentage of area covered by crystal violet stained cell colonies, also taking the intensity of the staining and therefore cell density into account. We demonstrate that these parameters alone or in combination allow for robust quantification of IC50 values of the cytotoxic effect of two staurosporines, UCN-01 and staurosporine (STS on human glioblastoma cells (T98G. The relation between the potencies of the two compounds compared very well with that obtained from an absorbance based method to quantify colony growth and to published data. The ColonyArea ImageJ plugin provides a simple and efficient analysis routine to quantitate assay data of one of the most commonly used cellular assays. The bundle is freely available for download as supporting information. We expect that ColonyArea will be of broad utility for cancer biologists, as well as clinical radiation scientists.

  17. Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy.

    Science.gov (United States)

    Yamauchi, Tomohiro; Saito, Hisayasu; Ito, Masaki; Shichinohe, Hideo; Houkin, Kiyohiro; Kuroda, Satoshi

    2014-12-01

    Autologous human bone marrow stromal cells (hBMSCs) should be expanded in the animal serum-free condition within clinically relevant periods in order to secure safe and effective cell therapy for ischemic stroke. This study was aimed to assess whether the hBMSCs enhance their proliferation capacity and provide beneficial effect in the infarct brain when cultured with platelet lysate (PL) and granulocyte-colony stimulating factor (G-CSF). The hBMSCs were cultured in the fetal calf serum (FCS)-, PL-, or PL/G-CSF-containing medium. Cell growth kinetics was analyzed. The hBMSCs-PL, hBMSC-PL/G-CSF, or vehicle was stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion 7 days after the insult. Motor function was assessed for 8 weeks, and the fate of transplanted hBMSCs was examined using immunohistochemistry. As the results, the hBMSCs-PL/G-CSF showed more enhanced proliferation than the hBMSCs-FCS and hBMSCs-PL. Transplantation of hBMSCs expanded with the PL- or PL/G-CSF-containing medium equally promoted functional recovery compared with the vehicle group. Histological analysis revealed that there were no significant differences in their migration, survival, and neural differentiation in the infarct brain between the hBMSCs-PL and hBMSCs-PL/G-CSF. These findings strongly suggest that the combination of PL and G-CSF may accelerate hBMSC expansion and serve safe cell therapy for patients with ischemic stroke at clinically relevant timing.

  18. Relationship between native-state solubility and non-native aggregation of recombinant human granulocyte colony stimulating factor: practical implications for protein therapeutic development.

    Science.gov (United States)

    Banks, Douglas D; Zhang, Jun; Siska, Christine C

    2014-10-06

    Prescreening methods are needed in the biotechnology industry for rapid selection of protein therapeutic candidates and formulations of low aggregation propensity. In recent reports solubility measurements have shown promise as one such method, although the connection between protein solubility and non-native aggregation is not well understood. In the present investigation, recombinant human granulocyte colony stimulating factor (rhGCSF) was used to explore this relationship since it was previously shown to rapidly undergo non-native aggregation/precipitation under physiological conditions in a reaction attenuated by the addition of sucrose [Krishnan, S.; et al. Biochemistry 2002, 41, 6422-6431]. Strong correlations were found between rhGCSF non-native aggregation and both solubility and thermal stability as a function of sucrose concentration. We believe these results make sense in the context of an rhGCSF aggregation mechanism where loss of monomer to insoluble aggregate is limited by association to an observable dimer from a less soluble (and aggregation competent) intermediate species that exists in a temperature sensitive pre-equilibrium with the native monomer. Both solubility and measures of conformational stability report on the position of this equilibrium and therefore the concentration of reactive intermediate. Interestingly, aggregation also correlated with rhGCSF solubility as a function of salting-in concentrations of phosphate since both are dependent on the colloidal stability of the reactive intermediate but not with conformational stability. In lieu of a complete understanding of the aggregation processes that limit protein therapeutic shelf life, these results highlight the potential of using simple solubility measurements as an additional tool in the biotechnology prescreening repertoire.

  19. Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats.

    Science.gov (United States)

    Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

    2015-12-01

    TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

  20. Characterization of pathogenic human monoclonal autoantibodies against GM-CSF.

    Science.gov (United States)

    Wang, Yanni; Thomson, Christy A; Allan, Lenka L; Jackson, Linda M; Olson, Melanie; Hercus, Timothy R; Nero, Tracy L; Turner, Amanda; Parker, Michael W; Lopez, Angel L; Waddell, Thomas K; Anderson, Gary P; Hamilton, John A; Schrader, John W

    2013-05-07

    The origin of pathogenic autoantibodies remains unknown. Idiopathic pulmonary alveolar proteinosis is caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We generated 19 monoclonal autoantibodies against GM-CSF from six patients with idiopathic pulmonary alveolar proteinosis. The autoantibodies used multiple V genes, excluding preferred V-gene use as an etiology, and targeted at least four nonoverlapping epitopes on GM-CSF, suggesting that GM-CSF is driving the autoantibodies and not a B-cell epitope on a pathogen cross-reacting with GM-CSF. The number of somatic mutations in the autoantibodies suggests that the memory B cells have been helped by T cells and re-entered germinal centers. All autoantibodies neutralized GM-CSF bioactivity, with general correlations to affinity and off-rate. The binding of certain autoantibodies was changed by point mutations in GM-CSF that reduced binding to the GM-CSF receptor. Those monoclonal autoantibodies that potently neutralize GM-CSF may be useful in treating inflammatory disease, such as rheumatoid arthritis and multiple sclerosis, cancer, and pain.

  1. Specters of Colonialism

    DEFF Research Database (Denmark)

    Muhr, Sara Louise; Azad, Salam

    2013-01-01

    organization, we show how an overarching colonial discourse – although not acknowledged – shapes the experience that foreign employees have of work. This leaves foreign workers in an integration dilemma, as they are expected to suppress home-country values and identities in order to become accepted, while...... at the same time they always are bound to fail to become ‘Swedish’ because of the same foreign origins. Although Swedish culture – partly by distancing itself from having a colonial past – has successfully built up an image of openness, we argue that without acknowledging and confronting the role...... that European colonial history has played in the shaping of national identity, Swedish organizations (and organizations in other western countries not assumed to have a colonial history) will not be able to integrate their foreign employees successfully....

  2. Post-Colonial Theory and Action Research

    Directory of Open Access Journals (Sweden)

    Jim Parsons

    2011-02-01

    Full Text Available This essay explores connections between post-colonial theory and action research. Post-colonial theory is committed to addressing the plague of colonialism. Action research, at its core, promises to problematize uncontested ‘colonial’ hegemonies of any form. Both post-colonial theory and action research engage dialogic, critically reflective and collaborative values to offer a fuller range of human wisdom. The authors contend that post-colonialism theory calls for justice and seeks to speak to social and psychological suffering, exploitation, violence and enslavement done to the powerless victims of colonization around the world by challenging the superiority of dominant perspectives and seeking to re-position and empower the marginalized and subordinated. In similar ways, action research works to eradicate oppression, powerlessness and worthlessness by affirming solidarity with the oppressed, helping humans move from passive to active and by fundamentally reshaping power. Because both post-colonial theory and action research position the insider or oppressed in an ethic of efficacy, it values community, relationships, communication and equality, and is committed to reciprocity, reflexivity and reflection. Thus, both hold the potential to help reconstruct conditions for a more democratic and just society

  3. Post-Colonial Theory and Action Research

    Directory of Open Access Journals (Sweden)

    Jim B. Parsons

    2011-04-01

    Full Text Available This essay explores connections between post-colonial theory and action research. Post-colonial theory is committed to addressing the plague of colonialism. Action research, at its core, promises to problematize uncontested ‘colonial’ hegemonies of any form. Both post-colonial theory and action research engage dialogic, critically reflective and collaborative values to offer a fuller range of human wisdom. The authors contend that post-colonialism theory calls for justice and seeks to speak to social and psychological suffering, exploitation, violence and enslavement done to the powerless victims of colonization around the world by challenging the superiority of dominant perspectives and seeking to re-position and empower the marginalized and subordinated. In similar ways, action research works to eradicate oppression, powerlessness and worthlessness by affirming solidarity with the oppressed, helping humans move from passive to active and by fundamentally reshaping power. Because both post-colonial theory and action research position the insider or oppressed in an ethic of efficacy, it values community, relationships, communication and equality, and is committed to reciprocity, reflexivity and reflection. Thus, both hold the potential to help reconstruct conditions for a more democratic and just society.

  4. Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons

    DEFF Research Database (Denmark)

    Nielsen, Susanne Dam; Clark, D R; Hutchings, M

    1999-01-01

    An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and ...

  5. Optimization of the culturing conditions of human umbilical cord blood-derived endothelial colony-forming cells under xeno-free conditions applying a transcriptomic approach

    NARCIS (Netherlands)

    Zeisberger, Steffen M.; Zoller, Stefan; Riegel, Mariluce; Chen, Shuhua; Krenning, Guido; Harmsen, Martin C.; Sachinidis, Agapios; Zisch, Andreas H.

    Establishment of fetal bovine serum (FBS)-free cell culture conditions is essential for transplantation therapies. Blood-derived endothelial colony-forming cells (ECFCs) are potential candidates for regenerative medicine applications. ECFCs were isolated from term umbilical cord blood units and

  6. Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Traumatic brain injury (TBI is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of

  7. Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes

    Science.gov (United States)

    2011-01-01

    results identified several new targets of EGCG, including epithelial neutrophil activating peptide-78 (ENA-78), granulocyte macrophage colony stimulation factor (GM-CSF), growth- related oncogene (GRO), GRO-α, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MCP-3, macrophage inflammatory protein-1beta (MIP-1β), granulocyte chemotactic protein-2 (GCP-2), MIP-3alpha, interferon-gamma-inducible protein-10 (IP-10), nucleosome assembly protein-2 (NAP-2) and leukemia inhibitory factor (LIF). The inhibitory effects of EGCG were mainly mediated by inhibiting the activation of NF-κB and c-Jun N-terminal Kinase (JNK)-MAPK in human chondrocytes. Conclusions Our results suggest that the potential of EGCG in OA treatment/prevention may be related to its ability to globally suppress the inflammatory response in human chondrocytes. These results identify additional new targets of EGCG and advocate that EGCG may be a potent chondroprotective agent in OA. PMID:21682898

  8. Colony Collapse Disorder

    Science.gov (United States)

    In CCD, the majority of worker bees in a colony disappear and leave behind a queen, plenty of food and a few nurse bees to care for remaining immature bees and the queen. EPA and USDA are working to understand and resolve this problem.

  9. Physiology of Continuous Bone Marrow Culture Derived Permanent Granulocyte-Macrophage Progenitor Cells

    Science.gov (United States)

    1983-08-01

    continuous marrow cultures. As shown in the accompAnying figures, there was no effect of Lithium Chloride (Figure 2), Sodium Selenite (Figure 3...tosis, respiratory burst, superoxide generation, degranulation and bactericidal capacity. When injected at 107 cells per day over 5 days these cells

  10. Effects of heat treatment and concentration of fish serum on cell growth in adhesion culture of Chinese hamster ovary cells

    OpenAIRE

    Fujiwara, Masashi; Tsukada, Ryohei; Shioya, Itaru; Takagi, Mutsumi

    2009-01-01

    The effects of heat treatment and concentration of fish serum (FS) on cell growth and human granulocyte-macrophage colony-stimulating factor (hGM-CSF) production in an adhesion culture of recombinant Chinese hamster ovary (CHO) cells, DR1000L4N, were investigated. The addition of heat treated FS instead of non-heat-treated FS improved cell growth in terms of cell density, which reached 60% that in 10% fetal calf serum (FCS)-containing medium (FCS medium). A decrease in FS concentration from 1...

  11. Fetal calf serum-free culture of Chinese hamster ovary cells employing fish serum

    OpenAIRE

    Fujiwara, M.; Tsukada, R.; Tsujinaga, Y.; Takagi, M

    2007-01-01

    The effects of fish serum on cell growth and human granulocyte-macrophage colony-stimulating factor (hGM-CSF) production in an adhesion culture of Chinese hamster ovary (CHO) cells DR1000L4N were investigated and compared with those of fetal calf serum (FCS). Although fish serum did not stimulate the initial adhesion of CHO cells to culture dishes, it prompted cell growth after cell adhesion with FCS for 24 h. The cell density in the fish serum medium reached 75% that in the FCS medium. Fish ...

  12. Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice.

    OpenAIRE

    J. A. Huffman; Hull, W M; Dranoff, G; Mulligan, R C; Whitsett, J A

    1996-01-01

    Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by homologous recombination caused alveolar proteinosis in mice. To further discern the role of GM-CSF in surfactant homeostasis, the synthesis of GM-CSF was directed to the respiratory epithelium of GM-CSF-hull mutant mice (GM-/-) with a chimeric gene expressing GM-CSF under the control of the promoter from the human surfactant protein-C (SP-C) gene. Transgenic mice bearing the SP-C-GM-CSF construct (SP-C-GM+) wer...

  13. 21 CFR 866.2180 - Manual colony counter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual colony counter. 866.2180 Section 866.2180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2180 Manual colony counter...

  14. 21 CFR 866.2170 - Automated colony counter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated colony counter. 866.2170 Section 866.2170 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2170 Automated colony...

  15. 'Mill's Liberal Project and Defence of Colonialism from a Post ...

    African Journals Online (AJOL)

    It aims to show that Mill's views on colonial rule were largely informed by his principle of liberty which, in turn, was based on his qualitative utilitarianism. The driving force behind his colonialism, as with his work in general, was his unwavering belief in the importance of human progress and development. Mill never believed ...

  16. Recycling Colonial Cultural Heritage

    DEFF Research Database (Denmark)

    Johansson, Troels Degn

    2017-01-01

    Danish art collective Superflex’ project Porcelain Pirates for the Zeeuws Museum in Middelburg, the Netherlands, is a fascinating and complex example of how a museum collection of artefacts from a colonial past may gain critical new meaning by means of cultural production and curatorial strategy...... as a nationally Dutch and regionally Zeelandish dimension. The installation and the television series is based on peculiar historical construction based on the Zeeuws Museem’s collection of porcelain: The Dutch capture of the Portuguese vessel San Jago which set sail from Goa bound for Lisbon in 1601 with one....... This paper provides an analysis of Superflex’ project with special reference to the cultural recycling of artefacts tied up with a sensitive colonial context. The analysis focuses especially on the role of the artefact and the way the project contributes to and challenges regional and national postcolonial...

  17. Human conjunctival epithelial cell responses to platelet-activating factor (PAF): signal transduction and release of proinflammatory cytokines.

    Science.gov (United States)

    Sharif, Najam A; Xu, Shouxi; Hellberg, Peggy E; Pang, Iok-Hou; Gamache, Daniel A; Yanni, John M

    2009-06-06

    The aims of the study were to characterize the signal transduction responses to platelet-activating factor (PAF) and to monitor the downstream effects of PAF on the production of proinflammatory cytokines in human conjunctival epithelial cells (HCECs). The generation of inositol phosphates ([(3)H]IPs) from [(3)H]phosphoinositide (PI) hydrolysis and the mobilization of intracellular calcium ([Ca(2+)](i)) were evaluated using ion exchange chromatography and Fura-2 fluorescence techniques, respectively. The production of the cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and granulocyte macrophage colony-stimulating factor [GM-CSF]) from PAF-stimulated HCECs was quantified using specific ELISA assays. Specific PAF antagonists were used to study the pharmacological aspects of PAF actions in HCECs. PAF (100 nM) maximally stimulated PI turnover in HCECs by 2.3+/-0.02 fold (n=21) above basal levels and with a potency (EC(50)) of 5.9+/-1.7 nM (n=4). PAF or its stabilized analog, methyl carbamyl (mc)PAF (EC(50)=0.8 nM), rapidly mobilized [Ca(2+)](i), which peaked within 30-60 s and remained elevated for 3 min. PAF (10 nM-1 microM) stimulated the release of the proinflammatory cytokines, IL-6, IL-8, and GM-CSF, 1.4-3.5 fold above basal levels. The effects of PAF (100 nM) on PI turnover and [Ca(2+)](i) were potently antagonized by the PAF antagonists, 1-o-hexadecyl-2-o-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (IC(50)=0.69 microM; K(i)=38 nM), methyl 2-(phenylthio)ethyl-1,4-dihydro-2,4,6-trimethyl-pyridine-3,5-dicsrboxylate (PCA-42481; IC(50)=0.89 microM; K(i)=50 nM), rac-3-(N-octadecylcarbomoyl)-2-methoxy) propyl-(2-thiazolioethyl) phosphate (CV-3988; IC(50)=13 microM; K(i)=771 nM), and (+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl (SM-10661; IC(50)=14 microM; K(i)=789 nM [n=3 for each antagonist]). PAF-induced production of IL-6, IL-8, and GM-CSF from HCECs was also blocked by these PAF antagonists (IC(50)=4.6- 8.6 microM). HCECs respond

  18. HONEY BEE COLONY PHEROMONES

    Directory of Open Access Journals (Sweden)

    M Dražić

    2001-09-01

    Full Text Available ABSTRACT Pheromones are chemicals produced as liquids by specialised cells or glands and transmitted into the environment as liquids or gases. In contrary to hormones, which are excreted in organism and have effect exclusively on organism that produced them, pheromones are excreted outside organism and effect on different individuals of the same species. Pheromones mediate nearly all aspects of honeybee colony life including social defence, brood care, mating, orientation, foraging and reproduction. Pheromone investigation has high economic importance. With use of pheromones it is possible to manipulate with pest insects on crops or to direct honeybees during pollination on target plants.

  19. Food and Coloniality

    Directory of Open Access Journals (Sweden)

    Adolfo Albán Achinte

    2011-05-01

    Full Text Available The author tackles the alimentary dimension of life, as something that goes beyond the simple act of ingesting food to acquire nutrients, to concentrate on the cultural implications of eating. To eat is more than to feed oneself, for eating is never by itself a wholly innocent act; that is, eating is never completely stripped from the social relationships of those gathered around a table.From this perspective, the article examines coloniality in all its forms (of power, of knowledge and of being, and shows their function as mechanisms of both alimentary enunciation and classification, that are responsible of the gastronomic supplantation of produce and food from the New World with the goods and customs that were so dear to European settlers (not forgetting that the influx of products and seasonings went also in the other direction. The colonizing project included thus, besides its religious, political and administrative pretenses, a gastronomical element, to be found in the eagerness of the colonizers to reproduce the alimentary imprint of their homeland in the new found territories, at least as far as the circumstances and the climate allowed it. Among all the facets the production of knowledge can acquire, gastronomy has been poorly studied —not to say completely silenced— in its role as a token of cultural divides, in which a coloniality of flavors and palates has been carried out.

  20. Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1.

    Directory of Open Access Journals (Sweden)

    Kholoud Arafat

    Full Text Available A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, salinomycin (2.5-5 µM for 7 days significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify salinomycin as a promising novel therapeutic agent for lung cancer.

  1. Colony Dimorphism in Bradyrhizobium Strains

    Science.gov (United States)

    Sylvester-Bradley, Rosemary; Thornton, Philip; Jones, Peter

    1988-01-01

    Ten isolates of Bradyrhizobium spp. which form two colony types were studied; the isolates originated from a range of legume species. The two colony types differed in the amount of gum formed or size or both, depending on the strain. Whole 7-day-old colonies of each type were subcultured to determine the proportion of cells which had changed to the other type. An iterative computerized procedure was used to determine the rate of switching per generation between the two types and to predict proportions reached at equilibrium for each strain. The predicted proportions of the wetter (more gummy) or larger colony type at equilibrium differed significantly between strains, ranging from 0.9999 (strain CIAT 2383) to 0.0216 (strain CIAT 2469), because some strains switched faster from dry to wet (or small to large) and others switched faster from wet to dry (or large to small). Predicted equilibrium was reached after about 140 generations in strain USDA 76. In all but one strain (CIAT 3030) the growth rate of the wetter colony type was greater than or similar to that of the drier type. The mean difference in generation time between the two colony types was 0.37 h. Doubling times calculated for either colony type after 7 days of growth on the agar surface ranged from 6.0 to 7.3 h. The formation of two persistent colony types by one strain (clonal or colony dimorphism) may be a common phenomenon among Bradyrhizobium strains. Images PMID:16347599

  2. Colonial Bilingual Heritage and Post-Colonial Myths in Cameroon's ...

    African Journals Online (AJOL)

    This article examines Cameroon's bilingual heritage and describes post-colonial attitudes and tendencies towards language and language use in the country's educational system. The intent is to show that Cameroon's bilingual heritage - a colonial legacy - has led to an unnecessary and chaotic national competition among ...

  3. Simultaneous Measurement of Human Hematopoietic Stem and Progenitor Cells In Blood Using Multi-color Flow Cytometry

    Science.gov (United States)

    Cimato, Thomas R.; Furlage, Rosemary L.; Conway, Alexis; Wallace, Paul K.

    2016-01-01

    Hematopoietic stem cells are the source of all inflammatory cell types. Discovery of specific cell surface markers unique to human hematopoietic stem (HSC) and progenitor (HSPC) cell populations has facilitated studies of their development from stem cells to mature cells. The specific marker profiles of HSCs and HSPCs can be used to understand their role in human inflammatory diseases. The goal of this study is to simultaneously measure HSCs and HSPCs in normal human venous blood using multi-color flow cytometry. Our secondary aim is to determine how G-CSF mobilization alters the quantity of each HSC and HSPC population. Here we show that cells within the CD34+ fraction of human venous blood contains cells with the same cell surface markers found in human bone marrow samples. Mobilization with G-CSF significantly increases the quantity of total CD34+ cells, blood borne HSCs, multipotent progenitors, common myeloid progenitors, and megakaryocyte erythroid progenitors as a percentage of total MNCs analyzed. The increase in blood borne common lymphoid and granulocyte macrophage progenitors with G-CSF treatment did not reach significance. G-CSF treatment predominantly increased the numbers of HSCs and multipotent progenitors in the total CD34+ cell population; common myeloid progenitors and megakaryocyte erythroid progenitors were enriched relative to total MNCs analyzed, but not relative to total CD34+ cells. Our findings illustrate the utility of multi-color flow cytometry to quantify circulating HSCs and HSPCs in venous blood samples from human subjects. PMID:26663713

  4. Colonial state formation without integration

    NARCIS (Netherlands)

    Alexopoulou Giannakitsa, Kleoniki; Juif, Dácil

    2017-01-01

    Samir Amin (1972) divided the African continent into three "macro-regions of colonial influence" with distinct socio-economic systems and labour practices: Africa of the colonial trade or peasant economy, Africa of the concession-owning companies, and Africa of the labour reserves. We argue that

  5. INDIGENOUS SPACES IN COLONIAL DOCUMENTS

    Directory of Open Access Journals (Sweden)

    Bartira Ferraz Barbosa

    2004-12-01

    Full Text Available The indigenous spaces constituted at the beginning of the colonial period represented a threat to the plans of implantation and development of the Portuguese-Brazilian colonial economy. Although little studied, they were distributed along the coast and inland of the captaincy of Pernambuco as the documents selected for this study point out. It is a question of the analysis of sources about cultures, spaces and indigenous frontiers, subjects that did not receive in-depth interpretations when studying the growth of Portuguese or Dutch colonial space.

  6. Genetic diversity affects colony survivorship in commercial honey bee colonies

    Science.gov (United States)

    Tarpy, David R.; vanEngelsdorp, Dennis; Pettis, Jeffrey S.

    2013-08-01

    Honey bee ( Apis mellifera) queens mate with unusually high numbers of males (average of approximately 12 drones), although there is much variation among queens. One main consequence of such extreme polyandry is an increased diversity of worker genotypes within a colony, which has been shown empirically to confer significant adaptive advantages that result in higher colony productivity and survival. Moreover, honey bees are the primary insect pollinators used in modern commercial production agriculture, and their populations have been in decline worldwide. Here, we compare the mating frequencies of queens, and therefore, intracolony genetic diversity, in three commercial beekeeping operations to determine how they correlate with various measures of colony health and productivity, particularly the likelihood of queen supersedure and colony survival in functional, intensively managed beehives. We found the average effective paternity frequency ( m e ) of this population of honey bee queens to be 13.6 ± 6.76, which was not significantly different between colonies that superseded their queen and those that did not. However, colonies that were less genetically diverse (headed by queens with m e ≤ 7.0) were 2.86 times more likely to die by the end of the study when compared to colonies that were more genetically diverse (headed by queens with m e > 7.0). The stark contrast in colony survival based on increased genetic diversity suggests that there are important tangible benefits of increased queen mating number in managed honey bees, although the exact mechanism(s) that govern these benefits have not been fully elucidated.

  7. Colonial Figures: Memories of Street Traders in the Colonial and Early Post-colonial Periods

    Directory of Open Access Journals (Sweden)

    Sheri Lynn Gibbings

    2012-12-01

    Full Text Available This article explores post-colonial memories about street traders among individuals who lived in the former colony of the Dutch East Indies. It argues that these narratives romanticize the relationship between Europeans and indigenous peoples. Street vendors are also used to differentiate between periods within colonial and post-colonial history. The nostalgic representation of interracial contact between Europeans and traders is contrasted with representations of other figures such as the Japanese and the nationalist. A recurring feature of these representations is the ability of Europeans to speak with street traders and imagine what they wanted and needed. The traders are remembered as a social type that transgressed politics and represented the neutrality of the economic sphere as a place for shared communication. The article concludes that the figure of the street vendor contributes to the nostalgic reinvention of the colony but is also used in narratives to differentiate between and mark changes across the colonial and post-colonial periods.

  8. Language teaching and graphic colonial.

    OpenAIRE

    Sandra Yaneth Chaparro Cardozo

    2015-01-01

    In the present study a reflection of the colonial baroque ornamentation from education and graphic blocks; analyzing aspects such as creating maps of the Basilica Church Cathedral Santiago de Tunja. This research tests the interpretation of the drawing and construction of ornamental figures of the native nature of the region in the colonies of the city of Tunja, Boyacá churches. This study of the visual reconstruction of the routes that make a group of children on the reinterpretation of the ...

  9. Delivery of GM-CSF to Protect against Influenza Pneumonia.

    Directory of Open Access Journals (Sweden)

    Renuka Subramaniam

    Full Text Available Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza.Granulocyte-macrophage colony stimulating factor (GM-CSF contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM. In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV.We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

  10. Granulocyte colony-stimulating factor increases CD4+ T cell counts of human immunodeficiency virus-infected patients receiving stable, highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Aladdin, H; Ullum, H; Dam Nielsen, S.

    2000-01-01

    Thirty human immunodeficiency virus (HIV)-infected patients with CD4+ T cell counts factor (G-CSF; 0.3 mg/mL 3 times...... a week) for 12 weeks. Blood samples were collected at specified time points. G-CSF treatment enhanced the total lymphocyte count (P=.002) and increased CD3+ (P=.005), CD4+ (P=.03), and CD8+ (P=.004) T cell counts as well as numbers of CD3-CD16+CD56+ NK cells (P=.001). The increases in CD4+ and CD8+ cell...... counts resulted from increases in CD45RO+ memory T cells and cells expressing the CD38 activation marker. Lymphocyte proliferative responses to phytohemagglutinin and Candida antigen decreased, whereas NK cell activity and plasma HIV RNA did not change during G-CSF treatment. After 24 weeks, all immune...

  11. Colonial Voting Rights

    NARCIS (Netherlands)

    Besselink, L.F.M.

    2008-01-01

    This case note discusses recent cases on voting rights for the European Parliament in Gibraltar and the Dutch Carribean countries, as well as the case of (lack of) voting rights for Carribean Dutch citizens for the national parliament in the European Court of Human Rights. It highlights the manner

  12. 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.

    Science.gov (United States)

    Briddell, R A; Hartley, C A; Smith, K A; McNiece, I K

    1993-09-15

    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.

  13. A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes

    Energy Technology Data Exchange (ETDEWEB)

    Roussel, M.F. (Univ. of Tennessee, Memphis (USA)); Shurtleff, S.A.; Downing, J.R. (Saint Jude Children' s Research Hospital, Memphis, TN (USA)); Sherr, C.J. (Univ. of Tennessee College of Medicine, Memphis (USA) Saint Jude Children' s Research Hospital, Memphis, TN (USA))

    1990-09-01

    Substitution of phenylalanine for tyrosine-809 in the human colony-stimulating factor 1 receptor (CSF-1R) inhibited its ability to transduce ligand-dependent mitogenic signals in mouse NIH 3T3 cells. When combined with an activating mutation at codon 301 that induces constitutive CSF-1R tyrosine kinase activity, the codon 809 mutation suppressed ligand-independent cell transformation. Comparative mapping tryptic phosphopeptides from mutant and wild-type CSF-1R indicated that tyrosine-809 is a site of ligand-dependent receptor phosphorylation in vivo. The mutant receptor was active as a tyrosine kinase in vitro and in vivo, underwent CSF-1-dependent association with a phosphatidylinositol 3-kinase, and induced expression of the protooncogenes c-fos and junB, underscoring its ability to trigger some of the known cellular responses to CSF-1. The mutant receptor is likely to be impaired in its ability to interact with critical cellular effectors whose activity is required for mitogenesis.

  14. Seabird Colonies in Western Greenland

    DEFF Research Database (Denmark)

    Boertmann, D.; Mosbech, A.; Falk, K.

    colonies in Greenland is compiled in a database maintained by NERI-AE. This report presents data on distribution, population numbers and population trends of 19 species of breeding colonial seabirds in western Greenland. Distributions are depicted on maps in Fig. 18-39. It is apparent that the major...... and range on the basis of the present material, due to too few and incomparable surveys. Only the Brünnich's guillemot is adequately studied to make conclusions on population trends (Kampp et al. 1994). However, our impressions of trends are given in Tab. 5. Species with decreasing populations are common...... eider, Brünnich's guillemot and Arctic tern, while at least great cormorant and great black-backed gull have shown range expansions and probably also population increases in recent years. The most important areas to breeding colonial seabirds are indicated on Fig. 40. Fig. 41 shows coastlines where...

  15. Language teaching and graphic colonial.

    Directory of Open Access Journals (Sweden)

    Sandra Yaneth Chaparro Cardozo

    2015-03-01

    Full Text Available In the present study a reflection of the colonial baroque ornamentation from education and graphic blocks; analyzing aspects such as creating maps of the Basilica Church Cathedral Santiago de Tunja. This research tests the interpretation of the drawing and construction of ornamental figures of the native nature of the region in the colonies of the city of Tunja, Boyacá churches. This study of the visual reconstruction of the routes that make a group of children on the reinterpretation of the design in the construction of maps of colonial baroque in the creation and graphic composition. Given the importance of aesthetics in the visual language manuals maples ornaments of the cathedral with a look from the pedagogy and education in studies of iconography Erwin Panofsky in understanding the phenomenon of space. 

  16. Colonial Voting Rights

    OpenAIRE

    Besselink, L.F.M.

    2008-01-01

    This case note discusses recent cases on voting rights for the European Parliament in Gibraltar and the Dutch Carribean countries, as well as the case of (lack of) voting rights for Carribean Dutch citizens for the national parliament in the European Court of Human Rights. It highlights the manner in which the ECJ and ECtHR are at odds on the same issue (but in different context), and how this context is determined by the way these courts wish to conceive of constitutional relations between E...

  17. Colonialism: nexus for myriad religious contentions in post-colonial ...

    African Journals Online (AJOL)

    The contact between African Traditional Religion (ATR) and Christianity is inextricably linked to European economic activities that culminated into colonialism. The contact was in fact, between two opposing cultures –African and European. Christianity since its introduction is perceived as an embodiment of Western culture, ...

  18. Colonial and post-colonial aspects of Australian identity.

    Science.gov (United States)

    Tranter, Bruce; Donoghue, Jed

    2007-06-01

    Since the 1988 Bicentennial and the 2001 centenary of federation celebrations colonial images have flourished in Australia, highlighting the roles of convicts and free settlers during early colonization. Old sites, such as Port Arthur have been re-invigorated, and in 2004 Tasmanians celebrated the bicentenary of 'white' settlement. However, social scientists have given little attention to the role of colonial and post-colonial figures and myths as aspects of Australian national identity. We seek to address this issue by examining how convicts, free settlers, bushrangers and ANZACs are associated with contemporary identity in Australia. We examine evidence from the 2003 Australian Survey of Social Attitudes and find that historical figures such as the ANZACs and post-World War II immigrants comprise important aspects of national identity. A substantial majority of Australians judged ANZACs to be important, countering recent claims of the 'demise of the digger'. Sporting heroes are also at the core of Australian identity. Colonial figures appear to be far less important, although views on national identity vary according to social location. In particular, left-wing, university educated, younger, postmaterialist Australians view convicts and bushrangers as relatively important, indicating the salience of the larrikin in Australian identity.

  19. Consensus on the use of neutrophil-stimulating hematopoietic growth factors in clinical practice : An international viewpoint

    NARCIS (Netherlands)

    Rusthoven, JJ; deVries, EGE; Dale, DC; Piccart, M; Glaspy, J; Hamilton, A

    Hematopoietic growth factors (CSFs) are now available for use in patients with myelosuppression due to congenital, acquired and therapy-induced conditions. Variations in the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in

  20. Changing Views on Colonial Heritage

    NARCIS (Netherlands)

    Roosmalen, P.K.M. van

    2003-01-01

    Within the context of a rational study and in order to arrive at a balanced appreciation of nineteenth and twentieth century heritage worldwide, architecture and town planning realized under colonial rule requires special attention. This paper describes the strengths and need for a revised vision of

  1. Ant Colony Optimization for Control

    NARCIS (Netherlands)

    Van Ast, J.M.

    2010-01-01

    The very basis of this thesis is the collective behavior of ants in colonies. Ants are an excellent example of how rather simple behavior on a local level can lead to complex behavior on a global level that is beneficial for the individuals. The key in the self-organization of ants is communication

  2. Recent Honey Bee Colony Declines

    Science.gov (United States)

    2007-06-20

    thrips; ants; butterflies; moths; bats ; and hummingbirds and other birds. 2 Berenbaum, M.R., University of Illinois, Statement before the... vampire mite (Varroa destructor) and the tracheal mite (Acarapis woodi), and also colony declines due to the pathogen Paenibacillus larvae.12 Other reasons

  3. The Vine and Olive Colony.

    Science.gov (United States)

    Albinski, Nan Bowman

    1985-01-01

    Traces the historical sources of "Some Plant Olive Trees," a utopian novel by Emma Gelders Sterne, which offers a fictional account of the Vine and Olive colony, one of the most colorful yet least known utopian communities of the nineteenth century. (AYC)

  4. Colonial adventures in tropical agriculture

    NARCIS (Netherlands)

    Buelens, Frans; Frankema, Ewout

    2016-01-01

    How profitable were foreign investments in plantation agriculture in the Netherlands Indies during the late colonial era? We use a new dataset of monthly quoted stock prices and dividends of international companies at the Brussels stock exchange to estimate the returns to investment in tropical

  5. Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells from human monocytes.

    Science.gov (United States)

    Mizuno, K; Okamoto, H; Horio, T

    2001-09-01

    Muramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelioid cell granulomas. We examined its effects on multinucleated-giant-cell (MGC) formation from monocytes. Supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated MGCs from monocytes. MDP significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not affect total MGCs. N-Acetylmuramyl-L-alanyl-L-isoglutamine, an MDP analogue, had no effect on MGC formation. MGCs were produced by conditioned medium from CD14(++)/CD16(-) monocytes. MDP enhanced the LGC fusion index from CD14(++)/CD16(-) monocytes. MGCs were not produced from CD14(+)/CD16(+) monocytes or immature dendritic cells induced by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL) 4 and only weakly produced from macrophage (M)-CSF- or GM-CSF-induced macrophages. Added MDP did not generate MGCs from CD14(+)/CD16(+) monocytes or dendritic cells but enhanced LGC formation from macrophages. Because IFN-gamma, IL-3, and GM-CSF reportedly are important in LGC induction, we added anti-IFN-gamma, anti-IL-3, or anti-GM-CSF monoclonal antibody (mAb) concomitantly to the monocyte culture treated with conditioned medium alone or plus MDP. Anti-IFN-gamma mAb completely abrogated MGC generation, whereas anti-GM-CSF and anti-IL-3 mAbs significantly inhibited LGCs. These findings suggest that CD14(++)/CD16(-) monocytes are fused to form LGCs by MDP derived from granulomatous-disease-causing pathogens with inflammatory mediators such as IFN-gamma, IL-3, and GM-CSF.

  6. Purification of human recombinant granulocyte colony stimulating ...

    African Journals Online (AJOL)

    In Escherichia coli, recombinant proteins were produced either as three dimensionally folded forms or as unfolded forms, inclusion body (IB). The formation of IB was a frequent consequence of high-level protein production and inadequacy of folding agents namely chaperones in the cytoplasm. The structure of the protein in ...

  7. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4....... Furthermore, the fraction of naive CD4 cells increased. These findings have implications for the design of immunotherapy or gene therapy protocols....

  8. Volumetric Analysis of 3-D-Cultured Colonies in Wet Alginate Spots Using 384-Pillar Plate.

    Science.gov (United States)

    Lee, Dong Woo; Choi, Yea-Jun; Lee, Sang-Yun; Kim, Myoung-Hee; Doh, Il; Ryu, Gyu Ha; Choi, Soo-Mi

    2017-10-01

    The volumetric analysis of three-dimensional (3-D)-cultured colonies in alginate spots has been proposed to increase drug efficacy. In a previously developed pillar/well chip platform, colonies within spots are usually stained and dried for analysis of cell viability using two-dimensional (2-D) fluorescent images. Since the number of viable cells in colonies is directly related to colony volume, we proposed the 3-D analysis of colonies for high-accuracy cell viability calculation. The spots were immersed in buffer, and the 3-D volume of each colony was calculated from the 2-D stacking fluorescent images of the spot with different focal positions. In the experiments with human gastric carcinoma cells and anticancer drugs, we compared cell viability values calculated using the 2-D area and 3-D volume of colonies in the wet and dried alginate spots, respectively. The IC 50 value calculated using the 3-D volume of the colonies (9.5 μM) was less than that calculated in the 2-D area analysis (121.5 μM). We observed that the colony showed a more sensitive drug response regarding volume calculated from the 3-D image reconstructed using several confocal images than regarding colony area calculated in the 2-D analysis.

  9. Existential Thoughts in Fanon's Post-Colonialism Discourse

    Science.gov (United States)

    Yeh, Chuan-Rong

    2013-01-01

    Frantz Fanon, a pioneer of post-colonial theory, attempted to seek some unbeknown possibilities through a Sartrean existentialism thought toward ethnic liberation and the fighting against imperialism. This article tries to enter Fanon's short life that was full of humanism and existentialist thought and to explore the hidden theoretical context…

  10. Towards a Remediation of Africa's Image: the Colonial Novel and ...

    African Journals Online (AJOL)

    Colonialist literature and history are replete with lots of misrepresentation about Africa as a continent and Africans as a people. Understandably, the African experience of slavery during the era of the obnoxious trade in human trafficking as well as the later experience of colonialism gave reins to sentiments and beliefs held ...

  11. Queen promiscuity lowers disease within honeybee colonies.

    Science.gov (United States)

    Seeley, Thomas D; Tarpy, David R

    2007-01-07

    Most species of social insects have singly mated queens, but in some species each queen mates with numerous males to create a colony with a genetically diverse worker force. The adaptive significance of polyandry by social insect queens remains an evolutionary puzzle. Using the honeybee (Apis mellifera), we tested the hypothesis that polyandry improves a colony's resistance to disease. We established colonies headed by queens that had been artificially inseminated by either one or 10 drones. Later, we inoculated these colonies with spores of Paenibacillus larvae, the bacterium that causes a highly virulent disease of honeybee larvae (American foulbrood). We found that, on average, colonies headed by multiple-drone inseminated queens had markedly lower disease intensity and higher colony strength at the end of the summer relative to colonies headed by single-drone inseminated queens. These findings support the hypothesis that polyandry by social insect queens is an adaptation to counter disease within their colonies.

  12. Triclosan-Induced Aminoglycoside-Tolerant Listeria monocytogenes Isolates Can Appear as Small-Colony Variants

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Hein-Kristensen, Line; Gram, Lone

    2014-01-01

    Exposure of the human food-borne pathogen Listeria monocytogenes to sublethal concentrations of triclosan can cause resistance to several aminoglycosides. Aminoglycoside-resistant isolates exhibit two colony morphologies: normal-size and pinpoint colonies. The purposes of the present study were...

  13. Intercellular Genomics of Subsurface Microbial Colonies

    Energy Technology Data Exchange (ETDEWEB)

    Ortoleva, Peter [Indiana Univ., Bloomington, IN (United States); Tuncay, Kagan [Indiana Univ., Bloomington, IN (United States); Gannon, Dennis [Indiana Univ., Bloomington, IN (United States); Meile, Christof [Indiana Univ., Bloomington, IN (United States)

    2007-02-14

    This report summarizes progress in the second year of this project. The objective is to develop methods and software to predict the spatial configuration, properties and temporal evolution of microbial colonies in the subsurface. To accomplish this, we integrate models of intracellular processes, cell-host medium exchange and reaction-transport dynamics on the colony scale. At the conclusion of the project, we aim to have the foundations of a predictive mathematical model and software that captures the three scales of these systems – the intracellular, pore, and colony wide spatial scales. In the second year of the project, we refined our transcriptional regulatory network discovery (TRND) approach that utilizes gene expression data along with phylogenic similarity and gene ontology analyses and applied it successfully to E.coli, human B cells, and Geobacter sulfurreducens. We have developed a new Web interface, GeoGen, which is tailored to the reconstruction of microbial TRNs and solely focuses on Geobacter as one of DOE’s high priority microbes. Our developments are designed such that the frameworks for the TRND and GeoGen can readily be used for other microbes of interest to the DOE. In the context of modeling a single bacterium, we are actively pursuing both steady-state and kinetic approaches. The steady-state approach is based on a flux balance that uses maximizing biomass growth rate as its objective, subjected to various biochemical constraints, for the optimal values of reaction rates and uptake/release of metabolites. For the kinetic approach, we use Karyote, a rigorous cell model developed by us for an earlier DOE grant and the DARPA BioSPICE Project. We are also investigating the interplay between bacterial colonies and environment at both pore and macroscopic scales. The pore scale models use detailed representations for realistic porous media accounting for the distribution of grain size whereas the macroscopic models employ the Darcy-type flow

  14. African colonial boundaries and nation-building

    African Journals Online (AJOL)

    HDS 10

    Britain, France, Germany, Portugal and Belgium. The aim was to stop the issue from degenerating into open war (Afigbo. 1990:129). One major aspect of Africa's colonial heritage is colonial boundaries. Many colonial boundaries in Africa date back to the Berlin conference of 1884-1885, which climaxed the scramble and ...

  15. Colonial adventures in tropical agriculture

    OpenAIRE

    Buelens, Frans; Frankema, Ewout

    2016-01-01

    How profitable were foreign investments in plantation agriculture in the Netherlands Indies during the late colonial era? We use a new dataset of monthly quoted stock prices and dividends of international companies at the Brussels stock exchange to estimate the returns to investment in tropical agriculture (1919–1938). We adopt the Dimson–March–Staunton method to compute real geometric annual average rates of return and assess our estimates in an international comparative perspective. We find...

  16. Honeybee immunity and colony losses

    Directory of Open Access Journals (Sweden)

    F. Nazzi

    2014-10-01

    Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

  17. Indigenous Customs and Colonial Law

    Directory of Open Access Journals (Sweden)

    Manaf Kottakkunnummal

    2014-03-01

    Full Text Available This article looks at the contesting articulations of gender, family, and religion in colonial South India. The article discusses the encounter between matrilineal customs and the Anglo-Muhammadan law in the site of Mappila Muslim matrilineal practices in colonial Malabar, of the Madras Presidency during c. 1910-1928. Young male members of the joint family used the language that matriliny is un-Islamic, and passed laws in the Legislative Assembly to demand that joint family property requires to be inherited in the patrilineal line. Three legislations were passed during the period of 1910-1940 to bring Muslim families in accordance with the ideal notions of familial organization existed in that period. The ideal notions were set up by the precepts of the Anglo-Muhammadan law, the orientalist knowledge of Islam, ideologies of colonial modernity, and dreams of caste and religious reform movements among the people of Malabar, and other neighboring states, Cochin and Travancore. In response to that, there was a re-articulation of customs and familial practices by using legal provisions available in the Islamic law, and an effort for justifying the practices to avoid the ruin of matriliny. Subsequently, the matrilineal Mappilas of Malabar retained matrilineal customs rather intact, though the gender relations and religious practices were re-articulated in the idioms of patriarchy and textuality.

  18. Terra Nullius: Colonial Violence in Prynne’s Acrylic Tips

    Directory of Open Access Journals (Sweden)

    Matthew Hall

    2016-06-01

    Full Text Available Examining J.H. Prynne’s 'Acrylic Tips' through a series of analogous readings, this paper identifies the location, characters, and themes of the poem. By examining the poem and the contiguities with 'Her Weasel’s Wild Returning', 'Acrylic Tips' is positioned against the historical decree of terra nullius over the sovereign land of Australia. The poem is read against and situated in the colonial and linguistic history of Australia. Read as a pastoral elegy, the poem depicts a hierarchy of human dominance over nature, which finds its ends in the colonial shearing shed, as well as the genetic laboratory. These positions are ultimately argued to be socio-political by-products of the colonial dominance of Indigenous culture and nature.

  19. Multi-elemental analysis of colonial and post-colonial Nigerian coins ...

    African Journals Online (AJOL)

    Multi-elemental analysis of colonial and post-colonial Nigerian coins by Proton Induced X-ray Emission (PIXE) spectrometry. ... A non-destructive physical method of ion beam analysis; PIXE was employed to investigate elemental properties of colonial and post-colonial Nigerian coins. The weights of the coins varied ...

  20. Deadly competition between sibling bacterial colonies

    Science.gov (United States)

    Be'Er, Avraham

    2011-03-01

    As a result of stress due to nutrient limitation or antibiotics, competing individual bacteria within a single colony may lyse sibling cells to release nutrients (cannibalism) or DNA (fratricide). However, we have recently shown that competition is not limited to individuals, but can occur at the colony level [A. Be'er et al., PNAS 106, 428 (2009); A. Be'er et al., PNAS 107, 6258 (2010).] In response to the presence of an encroaching sibling colony, Paenibacillus dendritiformis bacteria secrete a lethal protein, lysing cells at the interface between the colonies. Analysis of the proteins secreted by these competing sibling colonies, combined with a mathematical model, shows how colonies maintain their growth by self-regulating the secretion of two proteins: subtilisin (a well-known growth promoter), and Slf (a previously unknown protein, which is lethal). The results also explain why a single colony is not inhibited by its own secretions.

  1. Action of granulopoiesis-stimulating cytokines rhG-CSF, rhGM-CSF, and rmGM-CSF on murine haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC).

    Science.gov (United States)

    Hofer, M; Vacek, A; Weiterová, L

    2005-01-01

    The aim of this study was to provide new data to the knowledge of mechanisms by which recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) enhance the numbers of colonies growing from hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) in the murine bone marrow. The in vitro technique for cultivating GM-CFC from normal bone marrow cells was used. For evaluation of stimulatory actions of the drugs studied, the factors themselves or sera of mice given these factors were added to the cultures. The factors or the sera were present in the cultures either as the only potentially stimulatory agents or acted jointly with a suboptimum concentration of recombinant murine interleukin-3 (rmIL-3). It was found that both rhG-CSF and rmGM-CSF stimulate the proliferation of GM-CFC by a combination of direct mechanisms (direct actions on the target cells) and indirect effects (effects mediated through the induction of other cytokines and/or growth factors in the murine organism). The rhGM-CSF exhibited somewhat weaker in vitro effects in comparison with the other two factors and only indirect effects were noted. Additional in vivo experiments documented that, in spite of differences in mechanisms of action of the individual drugs studied on murine bone marrow cells in vitro, equal in vivo doses of the factors induce quantitatively similar effects on the production of GM-CFC in vivo.

  2. Affective Politics and Colonial Heritage

    DEFF Research Database (Denmark)

    Knudsen, Britta Timm; Andersen, Casper

    2017-01-01

    The article analyses the spatial entanglement of colonial heritage struggles through a study of the Rhodes Must Fall student movement at the University of Cape Town and the University of Oxford. We explore affective politics and the role heritage can play in the landscape of body politics. We aim...... to shed light over why statues still matter and we argue that affective politics – defined as politics that engage bodies immediately – is due to site-specific actions capable of going viral but likewise to non-photogenic scenes with indexical power. The decolonizing activism of the RMF movement mobilizes...... what we call an affective politics using bodies as main tool....

  3. The logic of hypersocial colonies

    DEFF Research Database (Denmark)

    Pedersen, Jes Søe

    2012-01-01

    It is no wonder that we are transfixed with fascination when we stand in the midst of an ocean of flowing ants within a single extensive society of one of the invasive species. Normal terms do not fit anymore: this is not just a colony, but a “supercolony.” The iconic supercolonial species...... is the Argentine ant, infamous as a pest and now very well studied, all the way from having its genome sequenced to its global distribution mapped. As the Argentine ant can be the key to understanding other supercolonial and/or invasive ants, it is very timely that Moffett's review (2012) focuses on how we...

  4. Alternative Modernities for Colonial Korea

    Directory of Open Access Journals (Sweden)

    Steven Lee

    2016-06-01

    Full Text Available Sunyoung Park. The Proletarian Wave: Literature and Leftist Culture in Colonial Korea, 1910–1945. Cambridge, MA: Harvard University Asia Center, 2015. 348 pp. $50 (cloth. Vladimir Tikhonov. Modern Korea and Its Others: Perceptions of the Neighbouring Countries and Korean Modernity. London: Routledge, 2016. 218 pp. $160 (cloth. It has become a global scholarly undertaking: how to rethink modernity so as to decouple it from Westernization (Chakrabarty 2000. Strategies have included foregrounding the plurality of history to disrupt linear progress; positing non-Western centers of modernity in, say, Moscow or Shanghai; and tracing anticolonial circuits connecting Asia to Africa to Latin America. The two recent books under review here add colonial-era Korea to such far-reaching discussions by situating the country across national boundaries. Interestingly, one connecting thread here is the alternative world system provided by the interwar, Soviet-oriented Left. The result is an unsettling of binaries that subsequently became entrenched during the Cold War: for example, north-south, socialist-nationalist, and, for literature, realist-modernist. But more broadly, pervading both books is the sense that history could have turned out differently—that revisiting northeast Asia’s porous borders in the early twentieth century reveals the Korean peninsula’s lost, internationalist potential...

  5. `Boy!': The Hinge of Colonial Double Talk

    Directory of Open Access Journals (Sweden)

    Anne M. Menke

    1991-01-01

    Full Text Available The French colonial enterprise in Africa enforced racial segregation, yet encouraged Africans to assimilate the French language, culture, and religion. The essay questions these contradictory policies through readings of Ferdinand Oyono's novels. It argues that a figure that embodies undecidability—the colonial servant known as the "boy"—is the locus of the denaturalization of the identities that were simultaneously institutionalized and denied by the Manichaean colonial world.

  6. Queen promiscuity lowers disease within honeybee colonies

    OpenAIRE

    Seeley, Thomas D; Tarpy, David R

    2006-01-01

    Most species of social insects have singly mated queens, but in some species each queen mates with numerous males to create a colony with a genetically diverse worker force. The adaptive significance of polyandry by social insect queens remains an evolutionary puzzle. Using the honeybee (Apis mellifera), we tested the hypothesis that polyandry improves a colony's resistance to disease. We established colonies headed by queens that had been artificially inseminated by either one or 10 drones. ...

  7. [Comparative study on the efficacy and safety between pegfilgrastim (PEG-rhG-CSF) and recombinant human granulocyte colony-stimulating factor in promoting hematopoietic recovery after allogeneic hematopoietic stem cell transplantation after hematological malignancy].

    Science.gov (United States)

    Yang, F; Sun, X D; Yuan, L; Zhang, J C; Hu, J W; Liu, N; Lou, X; Su, Y F; Yu, Z Y; Chen, J L; Li, Y H; Hu, L D; Chen, H; Jiang, M

    2017-10-14

    Objective: To observe the efficacy and safety between Pegfilgrastim (PEG-rhG-CSF) and Recombinant human granulocyte colony stimulating factor (rhG-CSF) in hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 157 patients after allo-HSCT were enrolled in this study from June 2015 to November 2016. Two agents of G-CSF were used to stimulate hematopoietic recovery after transplantation. There were 65 cases in PEG-rhG-CSF and 92 cases in rhG-CSF groups. Patients in PEG-rhG-CSF group were given a single subcutaneous dose of 6 mg on the first day and +8 d, while cases in rhG-CSF group were given in dose of 5 μg·kg(-1)·d(-1) by subcutaneous injection from +1 d continuing to neutrophils more than 1.5×10(9)/L, and then the indicators and survival rates in two groups after transplantation were compared. Results: ①There were no significant differences of the neutrophil implantation time[13.5 (8-12) d vs 13 (9-24) d, P =0.393] and platelet implantation time [14 (9-160) d vs 14 (9-92) d, P =0.094] between PEG-rhG-CSF and rhG-CSF groups respectively. There were no significant differences in terms of neutropenia period ( P =0.435) , number of cases who got fever during neutropenia ( P =0.622) , and the median time of fever in neutropenia period ( P =0.460) , respectively between the two groups. There were no significant differences of erythrocyte and platelet transfusions ( P =0.074, P =0.059) within 1 month after transplantation. ②There were no significant differences with regard to the incidences of acute GVHD[23.1% (15/65) vs 34.8% (32/92) , P =0.115], chronic GVHD[20.0% (13/65) vs 32.6% (32/92) , P =0.081], Ⅱ-Ⅳdegree of acute GVHD[30.0% (13/65) vs 30.4% (30/92) , P =0.287] and extensive chronic GVHD[9.2% (6/65) vs 20.7% (19/92) , P =0.135] between PEG-rhG-CSF and rhG-CSF groups. ③There were no significant differences in terms of disease free survival (DFS) (62.5% vs 61.4%, P =0.478) and overall survival (OS

  8. Number of colony-forming unit-Hill colonies among children and teenagers with obesity, dyslipidemia and breastfeeding history.

    Science.gov (United States)

    Salazar-Martinez, E; Rodriguez-Valentin, R; Albavera-Hernandez, C; Carreon-Rodriguez, A; Lazcano-Ponce, E

    2016-06-01

    The number of colony-forming unit (CFU)-Hill colonies has been proposed as a biomarker of vascular function and cardiovascular risk in adults but information about its role in children is scarce. This study evaluates the associations between obesity, cardiovascular risk factors and breastfeeding history with the numbers of CFU-Hill colonies in a sample of young people. We selected 49 children and teenagers between ages 10 and 17 (65.3% boys) from Mexican Health Care system. Physical activity and Anthropometric measures data were registered. CFU-Hill colonies were cultured from mononuclear cells obtained from venous blood. We detected inverse associations between the formation of CFU-Hill colonies and body mass index (BMI; β = -1.53; 95% confidence interval [CI], -1.92, -1.13), triglycerides (β = -0.26; 95%CI = -0.34, -0.18), total cholesterol (β = -0.13; 95%CI = -0.17, -0.08), Low Density Lipoprotein (LDL) (β = -0.20; 95%CI = -0.31, -0.09) and glucose (β = -0.37; 95%CI = -0.55, -0.18) using multivariate models. Breastfeeding duration showed a 1.46-colony increase for each month of breastfeeding (95%CI = 0.73, 2.18). CFU-Hill colony-forming capacity in children and teenagers was inversely associated with obesity, dyslipidemia and high blood levels of glucose. In contrast a longer breastfeeding duration was directly associated with an increased number of CFU-Hill colonies. However these results must be confirmed with further studies. Our findings support the importance of promoting breastfeeding and monitoring nutritional and metabolic status at an early age to prevent chronic disease development. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  9. VIRGINIA WOOLF'S FEMINISM AND A POST-COLONIAL LITERATURE

    Directory of Open Access Journals (Sweden)

    Marcio André Senem

    2008-07-01

    Full Text Available Feminism and Post-Colonialism are movements that emerged in the 20th century within the Social Sciences and that similarly attempt to deconstruct the hegemonically European and patriarchal literary canon in order to understand it and to modify the individuals’ performatic structures, allowing them a greater interaction with literature and all the areas of human knowledge and expression. From the work A room of one’s own (1928, written by the English author Virginia Woolf, we intend to make a relation of the expressions and concepts used by both movements, and to demonstrate the similarities in what they wish to say and to accomplish. Virginia Woolf’s work, that was directed to the emancipation of women and written for a conference given at a British University for a female audience, shows that women’s problems are similar to the silence imposed on the actions of the individuals from countries that are former colonies of European countries. Therefore, by studying the theories of post-structuralism, the intended analogy may be referred so as to discuss and to establish further more characteristics to the feminists movements and to post-colonialism itself. African black women, for example, who have been silenced by patriarchalism e by colonialism left as heritages, now find mechanisms to be heard and to express their knowledge about life and the world.

  10. Immunomodulatory Potential of the Polysaccharide-Rich Extract from Edible Cyanobacterium Nostoc commune

    Directory of Open Access Journals (Sweden)

    Hui-Fen Liao

    2015-11-01

    Full Text Available A dry sample of Nostoc commune from an organic farm in Pingtung city (Taiwan was used to prepare polysaccharide-rich (NCPS extract. The conditioned medium (CM from NCPS-treated human peripheral blood (PB-mononuclear cells (MNC effectively inhibited the growth of human leukemic U937 cells and triggered differentiation of U937 monoblast cells into monocytic/macrophagic lines. Cytokine levels in MNC-CMs showed upregulation of granulocyte/macrophage-colony stimulatory factor and IL-1β and downregulation of IL-6 and IL-17 upon treatment with NCPS. Moreover, murine macrophage RAW264.7 cells treated with NCPS exhibited the stimulatory effects of nitric oxide and superoxide secretion, indicating that NCPS might activate the immunity of macrophages. Collectively, the present study demonstrates that NCPS from N. commune could be potentially used for macrophage activation and consequently inhibited the leukemic cell growth and induced monocytic/macrophagic differentiation.

  11. Hallway gossip between Ras and PI3K pathways.

    Science.gov (United States)

    Emanuel, Peter D

    2014-05-01

    In this issue of Blood, Goodwin et al investigate the pathogenesis of juvenile myelomonocytic leukemia (JMML), demonstrating that mutant Shp2 induces granulocyte macrophage-colony-stimulating factor (GM-CSF) hypersensitivity and that the p110δ subunit of phosphatidylinositol 3-kinase (PI3K) further promotes this dysregulation

  12. Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis

    NARCIS (Netherlands)

    Greven, D. E. A.; Cohen, E. S.; Gerlag, D. M.; Campbell, J.; Woods, J.; Davis, N.; van Nieuwenhuijze, A.; Lewis, A.; Heasmen, S.; McCourt, M.; Corkill, D.; Dodd, A.; Elvin, J.; Statache, G.; Wicks, I. P.; Anderson, I. K.; Nash, A.; Sleeman, M. A.; Tak, P. P.

    2015-01-01

    Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue

  13. GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice.

    NARCIS (Netherlands)

    Plater-Zyberk, C.; Joosten, L.A.B.; Helsen, M.M.A.; Hepp, J.; Baeuerle, P.A.; Berg, W.B. van den

    2007-01-01

    OBJECTIVE: The pathogenic involvement of granulocyte-macrophage colony-stimulating factor (GM-CSF) in arthritis has been put forward. We have investigated the therapeutic effect of GM-CSF neutralisation in the streptococcal cell wall (SCW) arthritis model in mice. In this model, the pathogenic

  14. Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice

    NARCIS (Netherlands)

    Reed, JA; Ikegami, M; Robb, L; Begley, CG; Ross, G; Whitsett, JA

    Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GMCSF) or GM receptor common beta-chain (beta(c)) genes in mice [GM(-/-), beta(c)(-/-)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To

  15. Colonial Legal Reasoning in the Post-Colonial African State: A ...

    African Journals Online (AJOL)

    This article focuses on legal reasoning and legal epistemology within the African context. It examines the system of legal justice in post-colonial Africa and submits that because of the colonial legacy, post-colonial African legal reasoning is methodologically founded on empiricism and positivism. It avers that despite its merit ...

  16. Telephone Operators' Resistance to British Colonial Administration ...

    African Journals Online (AJOL)

    This paper aims to write the history of yet another form of resistance to colonial rule in British Africa with a focus on telephone operators in the erstwhile Cameroons Province. The pith and kernel of the paper therefore is to show how telephone operators resisted the colonial administration. This typology of resistance is yet to ...

  17. Print, Newspapers and Audiences in Colonial Kenya

    DEFF Research Database (Denmark)

    Frederiksen, Bodil Folke

    2011-01-01

    in newspapers. They depended on voluntary and political associations and anti-colonial struggles in Kenya and on links to nationalists in India and the passive resistance movement in South Africa. They sidestepped the European-dominated print culture and created an anti-colonial counter-voice. Editors insisted...

  18. Colonialism in Modern America: The Appalachian Case.

    Science.gov (United States)

    Lewis, Helen Matthews, Ed.; And Others

    The essays in this book illustrate a conceptual model for analyzing the social and economic problems of the Appalachian region. The model is variously called Colonialism, Internal Colonialism, Exploitation, or External Oppression. It highlights the process through which dominant outside industrial interests establish control, exploit the region,…

  19. Genetic Analysis of Termite Colonies in Wisconsin

    Science.gov (United States)

    R.A. Arango; D.A. Marschalek; F. Green III; K.F. Raffa; M.E. Berres

    2015-01-01

    The objective of this study was to document current areas of subterranean termite activity in Wisconsin and to evaluate genetic characteristics of these northern, peripheral colonies. Here, amplified fragment-length polymorphism was used to characterize levels of inbreeding, expected heterozygosity, and percent polymorphism within colonies as well as genetic structure...

  20. Predictive markers of honey bee colony collapse.

    Directory of Open Access Journals (Sweden)

    Benjamin Dainat

    Full Text Available Across the Northern hemisphere, managed honey bee colonies, Apis mellifera, are currently affected by abrupt depopulation during winter and many factors are suspected to be involved, either alone or in combination. Parasites and pathogens are considered as principal actors, in particular the ectoparasitic mite Varroa destructor, associated viruses and the microsporidian Nosema ceranae. Here we used long term monitoring of colonies and screening for eleven disease agents and genes involved in bee immunity and physiology to identify predictive markers of honeybee colony losses during winter. The data show that DWV, Nosema ceranae, Varroa destructor and Vitellogenin can be predictive markers for winter colony losses, but their predictive power strongly depends on the season. In particular, the data support that V. destructor is a key player for losses, arguably in line with its specific impact on the health of individual bees and colonies.

  1. Predictive markers of honey bee colony collapse.

    Science.gov (United States)

    Dainat, Benjamin; Evans, Jay D; Chen, Yan Ping; Gauthier, Laurent; Neumann, Peter

    2012-01-01

    Across the Northern hemisphere, managed honey bee colonies, Apis mellifera, are currently affected by abrupt depopulation during winter and many factors are suspected to be involved, either alone or in combination. Parasites and pathogens are considered as principal actors, in particular the ectoparasitic mite Varroa destructor, associated viruses and the microsporidian Nosema ceranae. Here we used long term monitoring of colonies and screening for eleven disease agents and genes involved in bee immunity and physiology to identify predictive markers of honeybee colony losses during winter. The data show that DWV, Nosema ceranae, Varroa destructor and Vitellogenin can be predictive markers for winter colony losses, but their predictive power strongly depends on the season. In particular, the data support that V. destructor is a key player for losses, arguably in line with its specific impact on the health of individual bees and colonies.

  2. The Impacts of English Colonial Terrorism and Genocide on Indigenous/Black Australians

    Directory of Open Access Journals (Sweden)

    Asafa Jalata

    2013-08-01

    Full Text Available This article critically explores the essence of colonial terrorism and its consequences on the indigenous people of Australia during their colonization and incorporation into the European-dominated racialized capitalist world system in the late 18th century. It uses multidimensional, comparative methods, and critical approaches to explain the dynamic interplay among social structures, human agency, and terror to explain the connection between terrorism and the emergence of the capitalist world system or globalization. Raising complex moral, intellectual, philosophical, ethical, and political questions, this article explores the essence, roles, and impacts of colonial terrorism on the indigenous Australians. First, the article provides background historical and cultural information. Second, it conceptualizes and theorizes colonial terrorism as an integral part of the capitalist world system. Specifically, it links capitalist incorporation and colonialism and various forms of violence to terrorism. Third, the article examines the structural aspects of colonial terrorism by connecting it to some specific colonial policies and practices. Finally, it identifies and explains different kinds of ideological justifications that the English colonial settlers and their descendants used in committing crimes against humanity.

  3. Form and metabolic scaling in colonial animals.

    Science.gov (United States)

    Hartikainen, Hanna; Humphries, Stuart; Okamura, Beth

    2014-03-01

    Benthic colonial organisms exhibit a wide variation in size and shape and provide excellent model systems for testing the predictions of models that describe the scaling of metabolic rate with organism size. We tested the hypothesis that colony form will influence metabolic scaling and its derivatives by characterising metabolic and propagule production rates in three species of freshwater bryozoans that vary in morphology and module organisation and which demonstrate two- and three-dimensional growth forms. The results were evaluated with respect to predictions from two models for metabolic scaling. Isometric metabolic scaling in two-dimensional colonies supported predictions of a model based on dynamic energy budget theory (DEB) and not those of a model based on fractally branching supply networks. This metabolic isometry appears to be achieved by equivalent energy budgets of edge and central modules, in one species (Cristatella mucedo) via linear growth and in a second species (Lophopus crystallinus) by colony fission. Allometric scaling characterised colonies of a three-dimensional species (Fredericella sultana), also providing support for the DEB model. Isometric scaling of propagule production rates for C. mucedo and F. sultana suggests that the number of propagules produced in colonies increases in direct proportion with the number of modules within colonies. Feeding currents generated by bryozoans function in both food capture and respiration, thus linking metabolic scaling with dynamics of self-shading and resource capture. Metabolic rates fundamentally dictate organismal performance (e.g. growth, reproduction) and, as we show here, are linked with colony form. Metabolic profiles and associated variation in colony form should therefore influence the outcome of biotic interactions in habitats dominated by colonial animals and may drive patterns of macroevolution.

  4. Growth of bacteria in 3-d colonies.

    Science.gov (United States)

    Shao, Xinxian; Mugler, Andrew; Kim, Justin; Jeong, Ha Jun; Levin, Bruce R; Nemenman, Ilya

    2017-07-01

    The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture, in which all cells have equal access to nutrients. In the real world, bacteria are more likely to live in physically structured habitats as colonies, within which individual cells vary in their access to nutrients. The dynamics of bacterial growth in such conditions is poorly understood, and, unlike that for liquid culture, there is not a standard broadly used mathematical model for bacterial populations growing in colonies in three dimensions (3-d). By extending the classic Monod model of resource-limited population growth to allow for spatial heterogeneity in the bacterial access to nutrients, we develop a 3-d model of colonies, in which bacteria consume diffusing nutrients in their vicinity. By following the changes in density of E. coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of this model to experimental data. The model accounts for the experimentally observed presence of a sub-exponential, diffusion-limited growth regime in colonies, which is absent in liquid cultures. The model predicts and our experiments confirm that, as a consequence of inter-colony competition for the diffusing nutrients and of cell death, there is a non-monotonic relationship between total number of colonies within the habitat and the total number of individual cells in all of these colonies. This combined theoretical-experimental study reveals that, within 3-d colonies, E. coli cells are loosely packed, and colonies produce about 2.5 times as many cells as the liquid culture from the same amount of nutrients. We verify that this is because cells in liquid culture are larger than in colonies. Our model provides a baseline description of bacterial growth in 3-d, deviations from which can be used to identify phenotypic heterogeneities and inter-cellular interactions that further contribute to the structure of bacterial

  5. Growth of bacteria in 3-d colonies.

    Directory of Open Access Journals (Sweden)

    Xinxian Shao

    2017-07-01

    Full Text Available The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture, in which all cells have equal access to nutrients. In the real world, bacteria are more likely to live in physically structured habitats as colonies, within which individual cells vary in their access to nutrients. The dynamics of bacterial growth in such conditions is poorly understood, and, unlike that for liquid culture, there is not a standard broadly used mathematical model for bacterial populations growing in colonies in three dimensions (3-d. By extending the classic Monod model of resource-limited population growth to allow for spatial heterogeneity in the bacterial access to nutrients, we develop a 3-d model of colonies, in which bacteria consume diffusing nutrients in their vicinity. By following the changes in density of E. coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of this model to experimental data. The model accounts for the experimentally observed presence of a sub-exponential, diffusion-limited growth regime in colonies, which is absent in liquid cultures. The model predicts and our experiments confirm that, as a consequence of inter-colony competition for the diffusing nutrients and of cell death, there is a non-monotonic relationship between total number of colonies within the habitat and the total number of individual cells in all of these colonies. This combined theoretical-experimental study reveals that, within 3-d colonies, E. coli cells are loosely packed, and colonies produce about 2.5 times as many cells as the liquid culture from the same amount of nutrients. We verify that this is because cells in liquid culture are larger than in colonies. Our model provides a baseline description of bacterial growth in 3-d, deviations from which can be used to identify phenotypic heterogeneities and inter-cellular interactions that further contribute to the structure of

  6. Swarming dynamics in bacterial colonies

    Science.gov (United States)

    Zhang, Hepeng; Be'Er, Avraham; Smith, Rachel; Florin, E.-L.; Swinney, Harry L.

    2009-11-01

    Swarming is a widespread phenomenon observed in both biological and non-biological systems. Large mammal herds, fish schools, and bird flocks are among the most spectacular examples. Many theoretical and numerical efforts have been made to unveil the general principles of the phenomenon, but systematic experimental studies have been very limited. We determine the characteristic velocity, length, and time scales for bacterial motion in swarming colonies of Paenibacillus dendritiformis growing on semi-solid agar substrates. The bacteria swim within a thin fluid layer, and they form long-lived jets and vortices. These coherent structures lead to anisotropy in velocity spatial correlations and to a two-step relaxation in velocity temporal correlations. The mean squared displacement of passive tracers exhibits a short-time regime with nearly ballistic transport and a diffusive long-time regime. We find that various definitions of the correlation length all lead to length scales that are, surprisingly, essentially independent of the mean bacterial speed, while the correlation time is linearly proportional to the ratio of the correlation length to the mean speed.

  7. The use of decoys to attract Least Terns (Sterna antillarum) to abandoned colony sites in New Jersey

    Science.gov (United States)

    Kotliar, Natasha B.; Burger, Joanna

    1984-01-01

    The number of Least Tern colony sites in New Jersey has declined in recent years. Decoys were used at two recently abandoned Least Tern colony sites in New Jersey to encourage nesting. The sites were chosen because of their apparent suitability as colony sites and the relative ease of protecting them from human disturbance and predators. Least Terns were observed flying over and landing at both sites, although nesting occurred at only one site. The effect of decoys was statically significant at the colony site used for nesting. At this site, 44.5% of the landings occurred in the plot containing decoys and only 10.6% o the landings were in the control plot. Nesting was initiated among the decoys. These results indicate that decoys can be used to attract Least Terns to abandoned colony sites and may be useful for managing Least Terns and other colonial nesting birds.

  8. The paroxysm of Plasmodium vivax malaria.

    Science.gov (United States)

    Karunaweera, Nadira D; Wijesekera, Subadra K; Wanasekera, Deepani; Mendis, Kamini N; Carter, Richard

    2003-04-01

    The paroxysms of Plasmodium vivax malaria are antiparasite responses that, although distressing to the human host, almost never impart serious acute pathology. Using plasma and blood cells from P. vivax patients, the cellular and noncellular mediators of these events have been studied ex vivo. The host response during a P. vivax paroxysm was found to involve T cells, monocytes and neutrophils, and the activity, among others, of the pyrogenic cytokines tumor necrosis factor alpha and interleukin 2 in addition to granulocyte macrophage-colony stimulating factor. However, interferon gamma activity, associated with serious acute pathogenesis in other studies on malaria, was absent. Induction of the cytokines active during a P. vivax paroxysm depends upon the presence of parasite products, which are released into the plasma before the paroxysm. Chemical identification of these natural parasite products will be important for our understanding of pathogenesis and protection in malaria.

  9. A simple agroinfiltration method for transient gene expression in plant leaf discs.

    Science.gov (United States)

    Matsuo, Kouki; Fukuzawa, Noriho; Matsumura, Takeshi

    2016-09-01

    In the present study, we developed a simple transient gene expression system based on Agrobacterium-mediated transformation. Vacuum infiltration was applied to leaf discs from Nicotiana benthamiana plants with Agrobacterium suspension solution under conventional vacuum conditions in a needleless plastic syringe. Model proteins, green fluorescent protein, β-glucuronidase, mouse granulocyte-macrophage colony-stimulating factor, and human fibroblast growth factor 1 were successfully expressed in leaf discs within 4 days after infiltration. In addition, the functional evaluation of viral RNA silencing suppressors, Artichoke mottled crinkle virus p19 protein, was also performed. Using this method, the contamination and diffusion of genetically modified bacterium to the environment and important transgenic plants were prevented. This method can be conducted without specialized apparatuses or large amounts of Agrobacterium suspension solutions; thus, the simultaneous evaluation of multiple vectors will be easily possible. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  10. Nomadic Research Practices in Early Childhood: Interrupting Racisms and Colonialisms

    Directory of Open Access Journals (Sweden)

    Veronica Pacini-Ketchabaw

    2011-12-01

    Full Text Available This paper considers how research practices on racialization in early childhood education might be reconceptualized when racialization is placed within relational intricacies and affects in multiple encounters. By foregrounding race and its emergence in multifarious, unpredictable ways in everyday encounters between human and non-human bodies, space, and discourse, the paper investigates how a movement toward research analyses that engage with both the materiality of race and its systemic and discursive formations might be used to constantly seek new ethical ways of responding to and acting against racisms and colonialism in early childhood.

  11. Colony Foundation in an Oceanic Seabird

    Science.gov (United States)

    Munilla, Ignacio; Genovart, Meritxell; Paiva, Vitor H.; Velando, Alberto

    2016-01-01

    Seabirds are colonial vertebrates that despite their great potential for long-range dispersal and colonization are reluctant to establish in novel locations, often recruiting close to their natal colony. The foundation of colonies is therefore a rare event in most seabird species and little is known about the colonization process in this group. The Cory’s shearwater (Calonectris diomedea) is a pelagic seabird that has recently established three new colonies in Galicia (NE Atlantic) thus expanding its distribution range 500 km northwards. This study aimed to describe the establishment and early progress of the new Galician populations and to determine the genetic and morphometric characteristics of the individuals participating in these foundation events. Using 10 microsatellite loci, we tested the predictions supported by different seabird colonization models. Possibly three groups of non-breeders, adding up to around 200 birds, started visiting the Galician colonies in the mid 2000’s and some of them eventually laid eggs and reproduced, thus establishing new breeding colonies. The Galician populations showed a high genetic diversity and a frequency of private alleles similar to or even higher than some of the large historical populations. Most individuals were assigned to several Atlantic populations and a few (if any) to Mediterranean colonies. Our study suggests that a large and admixed population is settling in Galicia, in agreement with predictions from island metapopulation models of colonization. Multiple source colonies imply that some birds colonizing Galicia were dispersing from very distant colonies (> 1500 km). Long-distance colonizations undertaken by relatively large and admixed groups of colonizers can help to explain the low levels of genetic structure over vast areas that are characteristic of most oceanic seabird species. PMID:26909694

  12. Evolutional Ant Colony Method Using PSO

    Science.gov (United States)

    Morii, Nobuto; Aiyoshi, Eitarou

    The ant colony method is one of heuristic methods capable of solving the traveling salesman problem (TSP), in which a good tour is generated by the artificial ant's probabilistic behavior. However, the generated tour length depends on the parameter describing the ant's behavior, and the best parameters corresponding to the problem to be solved is unknown. In this technical note, the evolutional strategy is presented to find the best parameter of the ant colony by using Particle Swarm Optimization (PSO) in the parameter space. Numerical simulations for benchmarks demonstrate effectiveness of the evolutional ant colony method.

  13. Increased survival of normal cells during laser photodynamic therapy: implications for ex vivo autologous bone marrow purging

    Energy Technology Data Exchange (ETDEWEB)

    Gulliya, K.S.; Matthews, J.L.; Fay, J.W.; Dowben, R.M.

    1988-01-01

    Laser light-induced, dye-mediated photolysis of leukemic cells was tested in an in vitro model for its efficacy in eliminating occult tumor cells for ex vivo autologous bone marrow purging. Merocyanine 540 (MC540) was mixed with acute promyelocytic leukemia (HL-60) cells in the presence of human albumin. This cell-dye mixture was irradiated with 514 nm argon laser light. Results show that in the presence of 0.1%, 0.25% and 0.5% albumin, laser light doses of 62.4 J/cm/sup 2/, 93.6 J/cm/sup 2/ and 109.2 J/cm/sup 2/, respectively, were required for a 5 log reduction in the survival of leukemic cells. Under identical conditions, 80% to 84% of the normal bone marrow cells and 41% of the granulocyte-macrophage colony forming cells survived. The number of surviving stromal cells was reduced (1+) compared to the untreated control (4+). Mixing of irradiated bone marrow cells with equal number of HL-60 cells did not interfere with the killing of HL-60 cells treated with MC540 and laser light. The non-specific cytotoxicity of laser light alone was less than 6% for normal bone marrow cells. These results suggest that the concentration of human albumin plays an important role in laser light-induced phototoxicity. This laser light-induced selective photolysis of leukemic cells can be used in ex vivo purging of tumor cell-contaminated bone marrow grafts to achieve very high survival rates of normal bone marrow cells and granulocyte-macrophage colony forming cells.

  14. Application of the antibiotic batumin for accurate and rapid identification of staphylococcal small colony variants

    Directory of Open Access Journals (Sweden)

    Churkina Larisa N

    2012-07-01

    Full Text Available Abstract Background Staphylococcus aureus is a major human pathogen causing significant morbidity and mortality. The S. aureus colonies in osteomyelitis, in patients with cystic fibrosis and patients with endoprosthesis rejection frequently have an atypical morphology, i.e. staphylococcal small-colony variants, which form a naturally occurring subpopulation of clinically important staphylococci. Identification of these small colony variants is difficult, because of the loss of typical phenotypic characteristics of these variants. We wanted to improve and simplify the diagnosis of staphylococcal infection using a diagnostic preparation, consisting of 5 μg batumin paper disks. Batumin possesses a unique selective activity against all studied Staphylococcus spp., whereas all other species tested thus far are batumin resistant. We assessed the efficacy of the batumin diagnostic preparation to identify staphylococcal small colony variants, isolated from osteomyelitis patients. Findings With the batumin diagnostic preparation, all 30 tested staphylococcal small-colony variants had a growth inhibition zone around the disk of minimum 25 mm, accordant with the inhibition zones of the parent strains, isolated from the same patients. Conclusions The batumin diagnostic preparation correctly identified the small-colony variants of S. aureus, S. haemolyticus and S. epidermidis as belonging to the genus Staphylococcus, which differ profoundly from parental strains and are difficult to identify with standard methods. Identification of staphylococcal small-colony variants with the batumin diagnostic preparation is technically simple and can facilitate practical laboratory work.

  15. Post-colonial identity in Greenland?

    DEFF Research Database (Denmark)

    Gad, Ulrik Pram

    2009-01-01

    In the gradual unravelling of Greenland’s colonial relationship to Denmark, an essentialist conceptualization of Greenlandic identity has played a significant role. However, both our scholarly understanding of post-colonial Greenlandic identity and the process towards independence for Greenland...... could be furthered by bringing politics back in. Based on a discourse analysis of the Greenlandic debate on language, this paper makes three claims: First, the identity projects promoted in Greenland are based on an essentialist conception of identity. Secondly, Greenlandic identity discourse combines...... elements of traditional Inuit culture and elements of colonial modernity. Thirdly, monolingual Greenlanders are those with the most to gain from abandoning the dichotomy of essentialist identities. Strategically, the paper suggests a post-post-colonial Greenlandic identity as a means of avoiding...

  16. Glendale Colony and Harvey Farms NPDES Permit

    Science.gov (United States)

    Under NPDES permit MT-0031819, Glendale Colony, Inc., and Harvey Farms, Inc. are authorized to discharge and must operate their facilities in accordance with provisions set forth herein.Indian Country on the Blackfeet Reserva

  17. Pathogen Webs in Collapsing Honey Bee Colonies

    Science.gov (United States)

    Cornman, R. Scott; Tarpy, David R.; Chen, Yanping; Jeffreys, Lacey; Lopez, Dawn; Pettis, Jeffery S.; vanEngelsdorp, Dennis; Evans, Jay D.

    2012-01-01

    Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD), otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV) and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees. PMID:22927991

  18. Pathogen webs in collapsing honey bee colonies.

    Directory of Open Access Journals (Sweden)

    R Scott Cornman

    Full Text Available Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD, otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees.

  19. Institutional Development and Colonial Heritage within Brazil*

    OpenAIRE

    Naritomi, Joana; Soares, Rodrigo Reis; Assunção, Juliano J.

    2009-01-01

    This paper analyzes the determinants of local institutions and distribution of political power within a constant 'macro-institutional' setting. We show that characteristics of Brazilian municipalities related to institutional quality and distribution of political power are partly inherited from the colonial histories experienced by different areas of the country. Municipalities with origins tracing back to the sugar-cane colonial cycle – characterized by a polarized and oligarchic socioeconom...

  20. Pattern Formation in a Bacterial Colony Model

    Directory of Open Access Journals (Sweden)

    Xinze Lian

    2014-01-01

    Full Text Available We investigate the spatiotemporal dynamics of a bacterial colony model. Based on the stability analysis, we derive the conditions for Hopf and Turing bifurcations. Furthermore, we present novel numerical evidence of time evolution of patterns controlled by parameters in the model and find that the model dynamics exhibit a diffusion controlled formation growth to spots, holes and stripes pattern replication, which show that the bacterial colony model is useful in revealing the spatial predation dynamics in the real world.

  1. Sustainable Development in Pre-Colonial, Colonial, and Post ...

    African Journals Online (AJOL)

    Although Africa may be the ancient origin of human civilization, “civilization” has since been a concept rooted in and reused by the West. Thus, Africa's true strength, its ingenuity for survival, must emerge from the shadows behind imperial discourse to successfully attain and sustain development. Keywords: Sustainable ...

  2. Automatic Evaluation of Colonies Growth rate of Yeasts incubated in Petri dishes using Mobile Platform

    Directory of Open Access Journals (Sweden)

    Alecsander Pereira Martins

    2015-10-01

    Full Text Available This paper proposes an automatic method based on computer vision implemented in mobile platform capable of monitoring the growth of microbial colonies incubated in Petri dishes. The developed optimized image processing algorithm performs this task without human intervention from images of colonies of the microorganism in different evolution phases. The contribution of this paper is the development of a fast and robust mobile tool to assist bioprocess experts in monitoring the growth of colonies without using the conventional error prone evaluation techniques. The obtained results successfully demonstrated dimensional alterations in colonies in a faster and more precise fashion when compared with the conventional method, with the additional advantage of versatility in producing reliable estimation of the growth rates with higher statistical significance.

  3. Space Colony from a Commercial Asteroid Mining Company Town

    Science.gov (United States)

    Taylor, Thomas C.; Grandl, Werner; Pinni, Martina; Benaroya, Haym

    2008-01-01

    Commercial mining towns on Earth become cities. Company towns need commerce to drive the growth and economy of early space colonies. Water is an early resource for camp consumables plus propellant export sales from asteroid mining operations at proposed burned out comets with water methane ice cores for sustainable growth over 50 years, financed from profits and capable with affordable logistics to support resource recovery. One co-author's perspective includes remote resource recovery sites on Earth. Other co-authors' experiences include architecture, lunar habitation, and architectural space colony concepts. This paper combines these experiences to propose commercial opportunities possible as mankind moves beyond one planet. Alaska's North Slope commercial history indicates that different multiple logistics transportation systems are required to reduce the risk to humans and families moved in before the oil flowed. Commercial enterprises have risked $20 billion and spent hundreds of billions in private money after profits were created. The lessons learned are applied to a burned out comet designated Wilson-Harrington (1979) and explores the architecture for early living within the burned out comet disk created from ice recovery and later sealed with an expected methane ice interior. Considered is the recovery of the resources, the transport of water back to Earth orbit or L-1, plus later the development of more comfortable space colony living. Commercial markets produce cities on Earth and the same can happen on Space Colonies. The key is an ``in place'' affordable commercial logistics system that can service, stimulate and sustain a 50-year commercial propellant market.

  4. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4...... and CD34 cells were measured. To examine the numbers of naive and memory type CD4 cells, CD4 cell coexpression of CD45RA and CD45RO was measured. Functionality of mobilized CD4 cells was examined by use of the proliferation assay and interleukin-2 ELISA. The number of CD34 cells increased from 1.50 to 20.......01/microL (P CD34 cells and CD4 cells in HIV-infected patients...

  5. Conquest, Colonial Education and Cultural Uprootedness in Africa ...

    African Journals Online (AJOL)

    There is disagreement between colonial and post-colonial Africanist historiography over the impact of colonial education on ... However, the latter are not quite agreeable to this position as they argue that colonial education had more negative effects than positive effects. Notwithstanding the benefits of Western education to ...

  6. Varroa-Virus Interaction in Collapsing Honey Bee Colonies

    DEFF Research Database (Denmark)

    Francis, Roy Mathew; Nielsen, Steen L.; Kryger, Per

    2013-01-01

    in honey bees and varroa mites from 23 colonies (15 apiaries) under three treatment conditions: Organic acids (11 colonies), pyrethroid (9 colonies) and untreated (3 colonies). Approximately 200 bees were sampled every month from April 2011 to October 2011, and April 2012. The 200 bees were split to 10...

  7. Gut yeast communities in Larus michahellis from various breeding colonies.

    Science.gov (United States)

    Al-Yasiri, Mohammed Hashim; Normand, Anne-Cécile; Piarroux, Renaud; Ranque, Stéphane; Mauffrey, Jean-François

    2017-06-01

    Yellow-legged gulls have been reported to carry antibiotic-resistant Enterobacteriaceae; however, the gut mycobiota of these birds has not yet been described. In this study, we analyzed the gut yeast communities in five yellow-legged gull breeding colonies along the Mediterranean littoral in southern France. Gull fecal samples were inoculated onto four types of culture media, including one supplemented with itraconazole. Yeast species richness, abundance, and diversity were estimated, and factorial analysis was used to highlight correspondences between breeding colonies. Yeast grew in 113 of 177 cultures, and 17 distinct yeast species were identified. The most frequent species were Candida krusei (53.5%), Galactomyces geotrichum (44.1%), C. glabrata (40.9%), C. albicans (20.5%), and Saccharomyces cerevisiae (18.1%). Gut yeast community structure in the gulls at both Pierre-Blanche Lagoon (PB) and Frioul Archipelago (F) were characterized by greater species richness and diversity than in those at the two cities of La Grande-Motte (GM) and Palavas-les-Flots (PF) as well as Riou Archipelago (R). Gulls in these latter three sites probably share a similar type of anthropogenic diet. Notably, the proportion of anthropic yeast species, including C. albicans and C. glabrata, in the gull mycobiota increased with gull colony synanthropy. Antifungal resistance was found in each of the five most frequent yeast species. We found that the gut yeast communities of these yellow-legged gulls include antifungal-resistant human pathogens. Further studies should assess the public health impact of these common synanthropic seabirds, which represent a reservoir and disseminator of drug-resistant human pathogenic yeast into the environment. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Colony formation in the cyanobacterium Microcystis.

    Science.gov (United States)

    Xiao, Man; Li, Ming; Reynolds, Colin S

    2018-02-22

    Morphological evolution from a unicellular to multicellular state provides greater opportunities for organisms to attain larger and more complex living forms. As the most common freshwater cyanobacterial genus, Microcystis is a unicellular microorganism, with high phenotypic plasticity, which forms colonies and blooms in lakes and reservoirs worldwide. We conducted a systematic review of field studies from the 1990s to 2017 where Microcystis was dominant. Microcystis was detected as the dominant genus in waterbodies from temperate to subtropical and tropical zones. Unicellular Microcystis spp. can be induced to form colonies by adjusting biotic and abiotic factors in laboratory. Colony formation by cell division has been induced by zooplankton filtrate, high Pb 2+ concentration, the presence of another cyanobacterium (Cylindrospermopsis raciborskii), heterotrophic bacteria, and by low temperature and light intensity. Colony formation by cell adhesion can be induced by zooplankton grazing, high Ca 2+ concentration, and microcystins. We hypothesise that single cells of all Microcystis morphospecies initially form colonies with a similar morphology to those found in the early spring. These colonies gradually change their morphology to that of M. ichthyoblabe, M. wesenbergii and M. aeruginosa with changing environmental conditions. Colony formation provides Microcystis with many ecological advantages, including adaption to varying light, sustained growth under poor nutrient supply, protection from chemical stressors and protection from grazing. These benefits represent passive tactics responding to environmental stress. Microcystis colonies form at the cost of decreased specific growth rates compared with a unicellular habit. Large colony size allows Microcystis to attain rapid floating velocities (maximum recorded for a single colony, ∼ 10.08 m h -1 ) that enable them to develop and maintain a large biomass near the surface of eutrophic lakes, where they may shade

  9. States of undress: nakedness and the colonial imagination.

    Science.gov (United States)

    Levine, Philippa

    2008-01-01

    The politics and aesthetics of nakedness was, for Victorians, both complex and slippery, the result of ambivalent nineteenth-century attitudes toward the unclothed body. This essay argues that such vexed attitudes about nudity and nakedness in Victorian Britain cannot fully be comprehended without reference to the experience of empire. Colonialism's seemingly timeless fascination with indigenous undress provoked a number of questions about human difference, evolution, and the nature of civilization. Analyzing different readings of nakedness in the worlds of science (especially anthropology), high art, and popular culture, this essay examines the enduring association between savagery and the lack of clothing.

  10. Colonial Army Formats in Africa and Post-Colonial Military Coups:

    African Journals Online (AJOL)

    BSOS USER

    military forces in colonial and early post-colonial Nigeria establish a legacy of coups in the armed forces in the post-independence era?10 The units of analysis are the coup events.11. In each case, inferences were drawn from the nationality and religious affiliation of coup plotters and participants, their motives, and the.

  11. Colonialism, customary law and the post-colonial state in Africa: the ...

    African Journals Online (AJOL)

    Colonialism became a fact of life in many African countries. An effect of colonialism especially in the former British colonized countries was the transplantation of the British legal system, which led to recognition of both systems and the gradual relegation of the indigenous system otherwise called customary law. The use and ...

  12. Grazer-induced colony formation in Scenedesmus: are there costs to being colonial?

    NARCIS (Netherlands)

    Lürling, M.; Van Donk, E.

    2000-01-01

    Grazer-induced colony formation in the common green alga Scenedesmus acutus may be interpreted as an anti-grazer defense. Costs are to be expected because otherwise the protected colonial morph would be the norm. Analysis of growth rates, light harvesting in terms of photosystem II (PSII) efficiency

  13. Colony Collapse Disorder: A Descriptive Study

    Science.gov (United States)

    vanEngelsdorp, Dennis; Evans, Jay D.; Saegerman, Claude; Mullin, Chris; Haubruge, Eric; Nguyen, Bach Kim; Frazier, Maryann; Frazier, Jim; Cox-Foster, Diana; Chen, Yanping; Underwood, Robyn; Tarpy, David R.; Pettis, Jeffery S.

    2009-01-01

    Background Over the last two winters, there have been large-scale, unexplained losses of managed honey bee (Apis mellifera L.) colonies in the United States. In the absence of a known cause, this syndrome was named Colony Collapse Disorder (CCD) because the main trait was a rapid loss of adult worker bees. We initiated a descriptive epizootiological study in order to better characterize CCD and compare risk factor exposure between populations afflicted by and not afflicted by CCD. Methods and Principal Findings Of 61 quantified variables (including adult bee physiology, pathogen loads, and pesticide levels), no single measure emerged as a most-likely cause of CCD. Bees in CCD colonies had higher pathogen loads and were co-infected with a greater number of pathogens than control populations, suggesting either an increased exposure to pathogens or a reduced resistance of bees toward pathogens. Levels of the synthetic acaricide coumaphos (used by beekeepers to control the parasitic mite Varroa destructor) were higher in control colonies than CCD-affected colonies. Conclusions/Significance This is the first comprehensive survey of CCD-affected bee populations that suggests CCD involves an interaction between pathogens and other stress factors. We present evidence that this condition is contagious or the result of exposure to a common risk factor. Potentially important areas for future hypothesis-driven research, including the possible legacy effect of mite parasitism and the role of honey bee resistance to pesticides, are highlighted. PMID:19649264

  14. Synthetic quorum sensing in model microcapsule colonies

    Science.gov (United States)

    Shum, Henry; Balazs, Anna C.

    2017-08-01

    Biological quorum sensing refers to the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. Designing synthetic materials systems that exhibit quorum sensing-like behavior could enable the fabrication of devices with both self-recognition and self-regulating functionality. Herein, we develop models for a colony of synthetic microcapsules that communicate by producing and releasing signaling molecules. Production of the chemicals is regulated by a biomimetic negative feedback loop, the “repressilator” network. Through theory and simulation, we show that the chemical behavior of such capsules is sensitive to both the density and number of capsules in the colony. For example, decreasing the spacing between a fixed number of capsules can trigger a transition in chemical activity from the steady, repressed state to large-amplitude oscillations in chemical production. Alternatively, for a fixed density, an increase in the number of capsules in the colony can also promote a transition into the oscillatory state. This configuration-dependent behavior of the capsule colony exemplifies quorum-sensing behavior. Using our theoretical model, we predict the transitions from the steady state to oscillatory behavior as a function of the colony size and capsule density.

  15. Colony collapse disorder: a descriptive study.

    Directory of Open Access Journals (Sweden)

    Dennis Vanengelsdorp

    Full Text Available BACKGROUND: Over the last two winters, there have been large-scale, unexplained losses of managed honey bee (Apis mellifera L. colonies in the United States. In the absence of a known cause, this syndrome was named Colony Collapse Disorder (CCD because the main trait was a rapid loss of adult worker bees. We initiated a descriptive epizootiological study in order to better characterize CCD and compare risk factor exposure between populations afflicted by and not afflicted by CCD. METHODS AND PRINCIPAL FINDINGS: Of 61 quantified variables (including adult bee physiology, pathogen loads, and pesticide levels, no single measure emerged as a most-likely cause of CCD. Bees in CCD colonies had higher pathogen loads and were co-infected with a greater number of pathogens than control populations, suggesting either an increased exposure to pathogens or a reduced resistance of bees toward pathogens. Levels of the synthetic acaricide coumaphos (used by beekeepers to control the parasitic mite Varroa destructor were higher in control colonies than CCD-affected colonies. CONCLUSIONS/SIGNIFICANCE: This is the first comprehensive survey of CCD-affected bee populations that suggests CCD involves an interaction between pathogens and other stress factors. We present evidence that this condition is contagious or the result of exposure to a common risk factor. Potentially important areas for future hypothesis-driven research, including the possible legacy effect of mite parasitism and the role of honey bee resistance to pesticides, are highlighted.

  16. Ant colony optimization algorithm for continuous domains based on position distribution model of ant colony foraging.

    Science.gov (United States)

    Liu, Liqiang; Dai, Yuntao; Gao, Jinyu

    2014-01-01

    Ant colony optimization algorithm for continuous domains is a major research direction for ant colony optimization algorithm. In this paper, we propose a distribution model of ant colony foraging, through analysis of the relationship between the position distribution and food source in the process of ant colony foraging. We design a continuous domain optimization algorithm based on the model and give the form of solution for the algorithm, the distribution model of pheromone, the update rules of ant colony position, and the processing method of constraint condition. Algorithm performance against a set of test trials was unconstrained optimization test functions and a set of optimization test functions, and test results of other algorithms are compared and analyzed to verify the correctness and effectiveness of the proposed algorithm.

  17. O ensino jesuítico no período colonial brasileiro: algumas discussões Discussions on jesuit teaching in Brazil during the colonial period

    Directory of Open Access Journals (Sweden)

    Alexandre Shigunov Neto

    2008-01-01

    Full Text Available O presente artigo pretende realizar uma análise do ensino jesuítico implementado no período colonial brasileiro e demonstrar que a estrutura escolar fundada pelos padres jesuítas no Brasil era adequada para o momento histórico vivenciado, levando-se em consideração quatro aspectos: os objetivos do Projeto Português para o Brasil; o projeto educacional Jesuítico; a própria estrutura social brasileira da época; e o modelo de homem necessário para a época Colonial. Os jesuítas, com seu Projeto Educacional, e os portugueses que vieram para a colônia brasileira em busca de riquezas, tiveram papel fundamental na formação da estrutura social, administrativa e produtiva da sociedade que estava sendo formada. Partindo do pressuposto de que o fenômeno educacional não é um fenômeno independente e autônomo da realidade social de determinado momento histórico, devemos analisar o projeto jesuítico levando-se em conta o desenvolvimento social e produtivo da época colonial. Assim, pode-se supor que o modelo educacional proposto pelos jesuítas, que pretendia formar um modelo de homem, baseado nos princípios escolásticos, era coerente com as necessidades e aspirações de uma sociedade em formação na primeira fase do período colonial brasileiro.Jesuit teaching in Brazil during the colonial period is analyzed. It may even be proved that the schooling structure established by the Jesuit fathers was extremely adequate for that specific historical period. Four aspects may be taken into account: the aims of the Portuguese Project for Brazil; the Jesuit Educational Project; the Brazilian social structure at that time; and the human model needed for the colonial period. The Jesuits' Educational Project and the Portuguese colonizers that came to the colony in search of wealth have an important role in the formation of the social, administrative and productive structure of a society in constant evolution. Since the educational phenomenon

  18. Production scheduling with ant colony optimization

    Science.gov (United States)

    Chernigovskiy, A. S.; Kapulin, D. V.; Noskova, E. E.; Yamskikh, T. N.; Tsarev, R. Yu

    2017-10-01

    The optimum solution of the production scheduling problem for manufacturing processes at an enterprise is crucial as it allows one to obtain the required amount of production within a specified time frame. Optimum production schedule can be found using a variety of optimization algorithms or scheduling algorithms. Ant colony optimization is one of well-known techniques to solve the global multi-objective optimization problem. In the article, the authors present a solution of the production scheduling problem by means of an ant colony optimization algorithm. A case study of the algorithm efficiency estimated against some others production scheduling algorithms is presented. Advantages of the ant colony optimization algorithm and its beneficial effect on the manufacturing process are provided.

  19. Arte da Performance e Guerra Colonial Portuguesa

    OpenAIRE

    Madeira, Cláudia

    2016-01-01

    UID/FIL/00183/2013 Este artigo propõe-se refletir sobre as relações entre a arte da performance portuguesa e a guerra colonial portuguesa. A simultaneidade no tempo histórico, entre os anos de 1960-1970, levaria a crer que, tal como aconteceu com as temáticas da Ditadura/Revolução, a guerra colonial pudesse ter sido abordada pela performance desenvolvida em Portugal. Contudo, paradoxalmente, se até recentemente não havia registos de nenhuma obra de arte da performance portuguesa desse perí...

  20. Abyssal fiction: common shares, colonial cleavages

    Directory of Open Access Journals (Sweden)

    Alexandre Montaury

    2016-12-01

    Full Text Available The paper aims to develop a reflection on the interaction between the legacies of colonialism and traditional symbolic and cultural practices in African Portuguese-speaking spaces. From a preliminary analysis of fictional texts of wide circulation in Brazil, aims to examine the cleavages, or “abyssal lines” that constitute experiences printed in the daily life of the former Portuguese colony of Cape Verde, Mozambique and Angola.---DOI: http://dx.doi.org/10.21881/abriluff.2016n17a378

  1. Behavioral Modulation of Infestation by Varroa destructor in Bee Colonies. Implications for Colony Stability.

    Directory of Open Access Journals (Sweden)

    Joyce de Figueiró Santos

    Full Text Available Colony Collapse Disorder (CCD has become a global problem for beekeepers and for the crops that depend on bee pollination. While many factors are known to increase the risk of colony collapse, the ectoparasitic mite Varroa destructor is considered to be the most serious one. Although this mite is unlikely to cause the collapse of hives itself, it is the vector for many viral diseases which are among the likely causes for Colony Collapse Disorder. The effects of V. destructor infestation differ from one part of the world to another, with greater morbidity and higher colony losses in European honey bees (EHB in Europe, Asia and North America. Although this mite has been present in Brazil for many years, there have been no reports of colony losses amongst Africanized Honey Bees (AHB. Studies carried out in Mexico have highlighted different behavioral responses by the AHB to the presence of the mite, notably as far as grooming and hygienic behavior are concerned. Could these explain why the AHB are less susceptible to Colony Collapse Disorder? In order to answer this question, we have developed a mathematical model of the infestation dynamics to analyze the role of resistance behavior by bees in the overall health of the colony, and as a consequence, its ability to face epidemiological challenges.

  2. Behavioral Modulation of Infestation by Varroa destructor in Bee Colonies. Implications for Colony Stability.

    Science.gov (United States)

    de Figueiró Santos, Joyce; Coelho, Flávio Codeço; Bliman, Pierre-Alexandre

    2016-01-01

    Colony Collapse Disorder (CCD) has become a global problem for beekeepers and for the crops that depend on bee pollination. While many factors are known to increase the risk of colony collapse, the ectoparasitic mite Varroa destructor is considered to be the most serious one. Although this mite is unlikely to cause the collapse of hives itself, it is the vector for many viral diseases which are among the likely causes for Colony Collapse Disorder. The effects of V. destructor infestation differ from one part of the world to another, with greater morbidity and higher colony losses in European honey bees (EHB) in Europe, Asia and North America. Although this mite has been present in Brazil for many years, there have been no reports of colony losses amongst Africanized Honey Bees (AHB). Studies carried out in Mexico have highlighted different behavioral responses by the AHB to the presence of the mite, notably as far as grooming and hygienic behavior are concerned. Could these explain why the AHB are less susceptible to Colony Collapse Disorder? In order to answer this question, we have developed a mathematical model of the infestation dynamics to analyze the role of resistance behavior by bees in the overall health of the colony, and as a consequence, its ability to face epidemiological challenges.

  3. Multiple-factor influences upon feeding flight rates at wading bird colonies (Alias: Are flight-line counts useful?)

    Science.gov (United States)

    Erwin, R.M.; Ogden, J.C.

    1979-01-01

    The temporal patterns of feeding, resting, and reproductive behavior in colonial wading birds have been studied by a number of investigators, both on a short-term (daily) and long-term (annual) basis. In coastal marine environments, activities at colonies are influenced by tides, time of day and phase of the nesting cycle. The purpose of this paper is twofold: (1) to examine the effects of tide, time of day (physical factors), nesting phase, colony site, and species identity (biological factors) on feeding flight rates at breeding colonies and, as a result of this, (2) to evaluate the usefulness of feeding flight counts as an index of the number of nests in the colony. Earlier work suggests that the relationship between the number of individuals flying to and from the nesting colony may be quite consistent with nest numbers. Thus, by monitoring flights from remote locations, observers might obtain relatively accurate census data while minimizing time and disturbance at colonies. Recent concern for the deleterious impact of humans at waterbird colonies underscores the need to investigate alternative census methods.

  4. In the post-colonial waiting room

    DEFF Research Database (Denmark)

    Adler-Nissen, Rebecca; Gad, Ulrik Pram

    2017-01-01

    ready for sovereignty. It explores a number of European overseas countries and territories. More specifically, it focuses on French dependencies in the Pacific and Indian Oceans, and North Atlantic Greenland constitutionally connected to Denmark. The immediate aim of anti-colonial struggles was to make...

  5. In the Post-Colonial Waiting Room

    DEFF Research Database (Denmark)

    Adler-Nissen, Rebecca; Gad, Ulrik Pram

    2017-01-01

    ready for sovereignty. It explores a number of European overseas countries and territories. More specifically, it focuses on French dependencies in the Pacific and Indian Oceans, and North Atlantic Greenland constitutionally connected to Denmark. The immediate aim of anti-colonial struggles was to make...

  6. 128 COLONIALISM: NEXUS FOR MYRIAD RELIGIOUS ...

    African Journals Online (AJOL)

    In this regard, Mercado writers that,. The missionary version of Christianity accepted by Africans (under colonial rule) can be described as hypocritical because many African Christians still patronizes ATR, especially, in times of emergency. This means that the influence of ATR is still strong especially in moment of crisis.

  7. Creole Jews: Negotiating Community in Colonial Suriname

    NARCIS (Netherlands)

    W.A. Vink (Wieke)

    2008-01-01

    textabstractThis study explores the ways in which a colonial domain affected identification processes among the Jews who had forged a Jewish community in Suriname since the mid seventeenth century. The history of the Surinamese Jews involves conflict, struggle and exclusion, but also cultural

  8. English Literatures in Post-Colonial Singapore

    Science.gov (United States)

    Dass, Rozita

    2015-01-01

    The emergence of a vibrant literary, culture and arts scene promotes Singapore's claims as a hub for arts and culture in the Asian region, and as a global arts city by the 21st century. The richness and variety of Singapore literature from the early post-colonial years are evident in the evolution of a Singapore literary culture. The diaspora of…

  9. 178 MULTIPLE COLONIALISM IN WESTERN SAHARA Macharia ...

    African Journals Online (AJOL)

    Administrator

    the French did when they claimed that Algeria was a province of France. Morocco exploited the prevailing international climate to advance its colonialistic proclivities at a time when territorial colonialism had become anathema internationally. That climate made the big powers, whether communistic or capitalistic, appear to ...

  10. Asexual propagation and regeneration in colonial ascidians.

    Science.gov (United States)

    Kürn, Ulrich; Rendulic, Snjezana; Tiozzo, Stefano; Lauzon, Robert J

    2011-08-01

    Regeneration is widely distributed among the metazoans. However, clear differences exist as to the degree of regenerative capacity: some phyla can only replace missing body parts, whereas others can generate entirely new individuals. Ascidians are animals that possess a remarkable regenerative plasticity and exhibit a great diversity of mechanisms for asexual propagation and survival. They are marine invertebrate members of the subphylum Tunicata and represent modern-day descendants of the chordate ancestor; in their tadpole stage they exhibit a chordate body plan that is resorbed during metamorphosis. Solitary species grow into an adult that can reach several centimeters in length, whereas colonial species grow by asexual propagation, creating a colony of genetically identical individuals. In this review, we present an overview of the biology of colonial ascidians as a paradigm for study in stem cell and regenerative biology. Focusing on botryllid ascidians, we introduce the potential roles played by multipotent epithelia and multipotent/pluripotent stem cells as source of asexual propagation and regenerative plasticity in the different budding mechanisms, and consider the putative mechanism of body repatterning in a non-embryonic scenario. We also discuss the involvement of intra-colony homeostatic processes in regulating budding potential, and the functional link between allorecognition, chimerism, and regenerative potential.

  11. German Colonialism and the Cameroonian Chieftaincy Institution ...

    African Journals Online (AJOL)

    German Colonialism and the Cameroonian Chieftaincy Institution, 1884-1916: The Politics of Convenience, Tyranny and Hegemony. ... Lagos Historical Review ... It demonstrates that notwithstanding the treatment meted out to chiefs by the German colonialists, African traditional rulers exploited their positions within the ...

  12. Order and instabilities in dense bacterial colonies

    Science.gov (United States)

    Tsimring, Lev

    2012-02-01

    The structure of cell colonies is governed by the interplay of many physical and biological factors, ranging from properties of surrounding media to cell-cell communication and gene expression in individual cells. The biomechanical interactions arising from the growth and division of individual cells in confined environments are ubiquitous, yet little work has focused on this fundamental aspect of colony formation. By combining experimental observations of growing monolayers of non-motile strain of bacteria Escherichia coli in a shallow microfluidic chemostat with discrete-element simulations and continuous theory, we demonstrate that expansion of a dense colony leads to rapid orientational alignment of rod-like cells. However, in larger colonies, anisotropic compression may lead to buckling instability which breaks perfect nematic order. Furthermore, we found that in shallow cavities feedback between cell growth and mobility in a confined environment leads to a novel cell streaming instability. Joint work with W. Mather, D. Volfson, O. Mondrag'on-Palomino, T. Danino, S. Cookson, and J. Hasty (UCSD) and D. Boyer, S. Orozco-Fuentes (UNAM, Mexico).

  13. Latin America: Essays Interpretating Colonial Legacy

    Directory of Open Access Journals (Sweden)

    María Pia López

    2013-12-01

    Full Text Available A large part of the Latin–American literature of the 19th and 20th century tried to deal with the national question intertwining different dimensions: the weight of colonial legacy, the cultural peculiarity of the nation and the inner relations between social classes and ethnic groups. Thinking the nation implied, in any case, to think the difference and the conflict with others, as well as the inner conflict and the logic of local colonialism. Analyzing some of these essays that played a central role in such process of recasting the origin of the nation, the author moves around three main axes: the formulation of dualist writings (colonial/national; white /indigenous; civilization/wilderness, the issue of language (the language inherited from the colonial experience versus the multilingual nature of indigenous Latin American societies, and the hypothesis about the birth of the nation – appointed to different groups – and its normal functioning as legitimization of the order sprung from independences.

  14. A Bicentennial Without a Puerto Rican Colony

    Science.gov (United States)

    Thomas, Piri

    1975-01-01

    The United States revolution of 1776 is said to lose validity in light of Puerto Rico's colonial situation under American rule. The plight of the Puerto Rican people is compared to that of the Euro-American settlers under the thumb-screw of British imperialism. (Author/AM)

  15. Project Final Report: HPC-Colony II

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Terry R [ORNL; Kale, Laxmikant V [University of Illinois, Urbana-Champaign; Moreira, Jose [IBM T. J. Watson Research Center

    2013-11-01

    This report recounts the HPC Colony II Project which was a computer science effort funded by DOE's Advanced Scientific Computing Research office. The project included researchers from ORNL, IBM, and the University of Illinois at Urbana-Champaign. The topic of the effort was adaptive system software for extreme scale parallel machines. A description of findings is included.

  16. An American termite in Paris: temporal colony dynamics.

    Science.gov (United States)

    Baudouin, Guillaume; Dedeine, Franck; Bech, Nicolas; Bankhead-Dronnet, Stéphanie; Dupont, Simon; Bagnères, Anne-Geneviève

    2017-12-01

    Termites of the genus Reticulitermes are widespread invaders, particularly in urban habitats. Their cryptic and subterranean lifestyle makes them difficult to detect, and we know little about their colony dynamics over time. In this study we examined the persistence of Reticulitermes flavipes (Kollar) colonies in the city of Paris over a period of 15 years. The aim was (1) to define the boundaries of colonies sampled within the same four areas over two sampling periods, (2) to determine whether the colonies identified during the first sampling period persisted to the second sampling period, and (3) to compare the results obtained when colonies were delineated using a standard population genetic approach versus a Bayesian clustering method that combined both spatial and genetic information. Herein, colony delineations were inferred from genetic differences at nine microsatellite loci and one mitochondrial locus. Four of the 18 identified colonies did not show significant differences in their genotype distributions between the two sampling periods. While allelic richness was low, making it hard to reliably distinguish colony family type, most colonies appeared to retain the same breeding structure over time. These large and expansive colonies showed an important ability to fuse (39% were mixed-family colonies), contained hundreds of reproductives and displayed evidence of isolation-by-distance, suggesting budding dispersal. These traits, which favor colony persistence over time, present a challenge for pest control efforts, which apply treatment locally. The other colonies showed significant differences, but we cannot exclude the possibility that their genotype distributions simply changed over time.

  17. Ireland – a test case of Post-colonialism / Post colonialism

    Directory of Open Access Journals (Sweden)

    Brenda Murray

    2006-05-01

    Full Text Available Contextualisation This review attempts to set the stage for post-colonial theorising, in the light of alternative representations of ‘whiteness’, on issues of gender, race and language within the discourse of equality. In this paper Ireland and the Irish provide a backdrop against which the nature and impact of colonialism on the colonised and the coloniser are explored. Many challenging questions emerge about the ideological basis of post colonial theory, not least when traditional paradigms of racism, as conveyed by the black / white dichotomy, are examined: Ireland presents a context, it is argued, where subjugation is of white on white. Linked to this is the language of the coloniser, a powerful hegemonic force which, in some situations, has been nurtured by the colonised and later developed into a text which is unique, producing a new literature which, it is asserted, truly invokes the ‘post colonial’. Abstract: Post-colonialism – essentially a critique of colonialism, is characterised by a process of disengagement from the colonial epoch and has taken many forms. In this article a set of phenomena are examined that have become inscribed in the cultures of the colonised with a view to identifying alternative cultural origins and dispositions recovered in this post-colonial era. Ireland and the Irish provide the background context of this exploration into perspectives generated by the peripheral or post-colonial nations. Globalisation, too, has had a role to play in the increasing de-territorialisation of communities as a result of cross-frontier mobility, increased intra-community mobility and new communication technologies. A critical reflection on the process of disengagement leads the author to conclude that we must come to recognise new cultural forms which are accepting of a heterogeneous and inclusive society: one which is not characterised by difference.

  18. Requirement of the agr Locus for Colony Spreading of Staphylococcus aureus

    NARCIS (Netherlands)

    Tsompanidou, Eleni; Sibbald, Mark J. J. B.; Chlebowicz, Monika A.; Dreisbach, Annette; Back, Jaap Willem; van Dijl, Jan Maarten; Buist, Girbe; Denham, Emma L.

    The important human pathogen Staphylococcus aureus is known to spread on soft agar plates. Here, we show that colony spreading of S. aureus involves the agr quorum-sensing system. This finding can be related to the agr-dependent expression of biosurfactants, such as phenol-soluble modulins,

  19. Growth pattern of the surface of fungus Aspergillus colony

    Science.gov (United States)

    Matsuura, Shu; Miyazima, Sasuke

    1992-05-01

    Aspergillus oryzae colonies were grown under various glucose concentrations, temperatures, and agar concentrations, and the effects on the pattern were investigated. Patterns of colony were found to vary from uniform to diffusion-limited aggregation type.

  20. Colonial Conflicts in Contemporary Northern Ghana: A Historical ...

    African Journals Online (AJOL)

    Colonial Conflicts in Contemporary Northern Ghana: A Historical Prognosis of the British Colonial Factor in the Nawuri-Gonja and Mamprusi-Kusasi Conflicts. ... Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL ...

  1. Purification of Helicobacter suis Strains From Biphasic Cultures by Single Colony Isolation: Influence on Strain Characteristics.

    Science.gov (United States)

    Liang, Jungang; De Bruyne, Ellen; Ducatelle, Richard; Smet, Annemieke; Haesebrouck, Freddy; Flahou, Bram

    2015-06-01

    Helicobacter (H.) suis causes gastritis and decreased weight gain in pigs. It is also the most prevalent non-Helicobacter pylori Helicobacter species in humans with gastric disease. H. suis is extremely fastidious, and so far, biphasic culture conditions were essential for isolation and culture, making it impossible to obtain single colonies. Hence, cultures obtained from an individual animal may contain multiple H. suis strains, which is undesirable for experiments aiming for instance at investigating H. suis strain differences. Pure cultures of H. suis were established by growing bacteria as colonies on 1% brucella agar plates, followed by purification and enrichment by biphasic subculture. Characteristics of these single colony-derived strains were compared with those of their parent strains using multilocus sequence typing (MLST) and by studying bacterium-host interactions using a gastric epithelial cell line and Mongolian gerbil model. The purification/enrichment procedure required a nonstop culture of several weeks. For 4 of 17 H. suis strains, MLST revealed differences between parental and single colony-derived strains. For three of four single colony-derived strains tested, the cell death-inducing capacity was higher than for the parental strain. One single colony-derived strain lost its capacity to colonize Mongolian gerbils. For the four other strains tested, colonization capacity and histopathologic changes were similar to what has been described when using strains with only a history of limited biphasic culture. A method was developed to obtain single colony-derived H. suis strains, but this procedure may affect the bacterial genotype and phenotype. © 2015 John Wiley & Sons Ltd.

  2. Does genetic diversity hinder parasite evolution in social insect colonies?

    DEFF Research Database (Denmark)

    Hughes, William Owen Hamar; Boomsma, Jacobus Jan

    2006-01-01

    Polyandry is often difficult to explain because benefits of the behaviour have proved elusive. In social insects, polyandry increases the genetic diversity of workers within a colony and this has been suggested to improve the resistance of the colony to disease. Here we examine the possible impact...... hinder the ability of parasites to adapt while cycling within social insect colonies....

  3. Juvenile colonies of the genus Pyrostremma Garstang, 1929 (Tunicata, Thaliacea)

    NARCIS (Netherlands)

    Soest, van R.W.M.

    1974-01-01

    Four remarkable dome-shaped, apparently juvenile colonies, belonging to the genus Pyrostremma Garstang, 1929, are described from the Bermuda area. Comparison with juvenile colonies of P.agassizi (Ritter & Byxbee, 1905), and with larger colonies, fragments and loose zooids of P.agassizi and

  4. The impact of colonial legacies and globalization processes on ...

    African Journals Online (AJOL)

    In this paper, I postulate that forced migration in modern Africa is largely explained by factors deeply rooted in colonial legacies and the globalization process. For example, among the colonial historical factors someone may identify land alienation that still fuels conflicts in Zimbabwe, the colonial military doctrine based on ...

  5. Kif Tebbi, the colonial archive, between sedimentation and connective memory

    Directory of Open Access Journals (Sweden)

    Gabriele Proglio

    2016-03-01

    Full Text Available This essay analyzes Kif Tebbi, a colonial novel by Luciano Zuccoli, in theoretical and interpretative perspective of the colonial archive. The aim is to problematize and deconstruct the colonial discourse of this writing from the cultural memories' point of view. In particular, the article will discuss two different forms of memory: the sedimentation and connective memory.

  6. A Post-Colonial Reading of Affirmative Action in Fiji.

    Science.gov (United States)

    Puamau, Priscilla Qolisaya

    2001-01-01

    Presents a post-colonial reading of affirmative action (AA) policies in Fiji, arguing that AA was a deliberate response by various predominantly indigenous Fijian post-colonial governments to counter the effects of a discriminatory colonial history that produced significant educational and employment inequality. Analyzes the mixed outcomes of AA…

  7. Colonial and Post-Independence Agricultural Policies in Eastern ...

    African Journals Online (AJOL)

    Prior to colonial administration, agriculture was very highly regarded because it assured the people of supply of food; stimulated a degree of urbanization and ... paper assesses the various colonial and post-colonial agricultural policies in Eastern Nigeria up to 1980, with a view to showing their impact on rural development.

  8. Colonial land policies in Lagos | Davies | Lagos Historical Review

    African Journals Online (AJOL)

    Land policies in colonial Lagos were variegated. They alternated between freehold at inception of colonialism in 1861, and customary tenure at the beginning of the twentieth century and later coalesced into a combination of both. The variegated nature of the colonial government's land policies created a lot of confusion in ...

  9. Regulaciones de la vida urbana colonial

    Directory of Open Access Journals (Sweden)

    Jorge Núñez Sánchez

    2006-11-01

    Full Text Available Este ensayo analiza ciertas normas dictadas por la Corona con el propósito de regular la vida urbana a lo largo del período colonial. El artículo centra su estudio en algunas disposiciones que buscaban refrenar el desorden público y mantener el orden y las normas del "buen vivir". Bajo esta perspectiva, se analizan algunas prácticas culturales que se apartaban de estas regulaciones, entre las que se incluyeron los albazos y carnavales. Muchas de estas manifestaciones fueron percibidas por el poder colonial como muestras de primitivismo latente. No obstante, el juego de carnaval, entre otras prácticas, se mantuvo reacio a acatar estas regulaciones.

  10. In the post-colonial waiting room

    DEFF Research Database (Denmark)

    Adler-Nissen, Rebecca; Gad, Ulrik Pram

    2017-01-01

    This chapter investigates this puzzle of choosing non-sovereignty in a postcolonial setting. Historically, the question of freedom from imperial hegemony has been linked to how Western colonialism involved keeping the colonized in ‘the waiting room of history’ by insisting that they were not yet...... ready for sovereignty. It explores a number of European overseas countries and territories. More specifically, it focuses on French dependencies in the Pacific and Indian Oceans, and North Atlantic Greenland constitutionally connected to Denmark. The immediate aim of anti-colonial struggles was to make...... acknowledge. A number of overseas territories take alternative routes to agency; not by resisting the norm of sovereignty - but by creatively articulating it beyond its claim to represent an 'either/or' distinction. The chapter demonstrates that territories not formally decolonized may very well perform...

  11. Designing communicating colonies of biomimetic microcapsules

    OpenAIRE

    Kolmakov, German V.; Yashin, Victor V.; Levitan, Steven P.; Balazs, Anna C.

    2010-01-01

    Using computational modeling, we design colonies of biomimetic microcapsules that exploit chemical mechanisms to communicate and alter their local environment. As a result, these synthetic objects can self-organize into various autonomously moving structures and exhibit ant-like tracking behavior. In the simulations, signaling microcapsules release agonist particles, whereas target microcapsules release antagonist particles and the permeabilities of both capsule types depend on the local part...

  12. Ant colony optimization and constraint programming

    CERN Document Server

    Solnon, Christine

    2013-01-01

    Ant colony optimization is a metaheuristic which has been successfully applied to a wide range of combinatorial optimization problems. The author describes this metaheuristic and studies its efficiency for solving some hard combinatorial problems, with a specific focus on constraint programming. The text is organized into three parts. The first part introduces constraint programming, which provides high level features to declaratively model problems by means of constraints. It describes the main existing approaches for solving constraint satisfaction problems, including complete tree search

  13. Ant colony optimization and stochastic gradient descent.

    Science.gov (United States)

    Meuleau, Nicolas; Dorigo, Marco

    2002-01-01

    In this article, we study the relationship between the two techniques known as ant colony optimization (ACO) and stochastic gradient descent. More precisely, we show that some empirical ACO algorithms approximate stochastic gradient descent in the space of pheromones, and we propose an implementation of stochastic gradient descent that belongs to the family of ACO algorithms. We then use this insight to explore the mutual contributions of the two techniques.

  14. Labour and Health in Colonial Nigeria

    OpenAIRE

    Vellore Arthi; James Fenske

    2013-01-01

    We examine the determinants of time allocation and child labour in a year-long panel of time-use data from colonial Nigeria. Using quantitative and ethnographic approaches, we show that health shocks imposed time costs on individuals. Whether individuals could recruit substitutes depended on social standing, urgency of work, and type of illness. Child labour did not systematically respond to temporary parental illness, but could replace a permanently disabled adult. Child labour was coordinat...

  15. Influence of feeding bee colonies on colony strenght and honey authenticity

    Directory of Open Access Journals (Sweden)

    Andreja KANDOLF BOROVŠAK

    2015-12-01

    Full Text Available For the natural development of bee colonies, there is the need for appropriate nutrition. Lack of natural honey flow must be supplemented by feeding bee colonies with sugar syrups or candy paste. This supplementary feeding encourages brood breeding and forage activity, whereby stronger colonies collect more honey. Sugar syrups can cause honey adulteration, which is more frequent with the reversing of the brood combs with the bee food, with the combs moved from the brood chamber to the upper chamber. Authentication of honey from the standpoint of the presence of sugar syrup is very complex, because there is no single method by which honey adulteration can be reliably confirmed. Feeding the colonies in spring should result in stronger colonies and hence the collection of more honey in the brood chambers. The objective of the present study was to determine whether this has effects also on honey authenticity, and to discover a simple method for detection of honey adulteration. The colonies were fed with candy paste that had added yeast and blue dye, to provide markers for detection of honey adulteration. The strength of the colonies and quantity of honey in the brood chambers were monitored. The results of the analysis of stable isotope and activity of foreign enzymes were compared with the results of yeast quantity and colour of the honey (absorbance, L*, a*, b* parameters. Detection of yeast in the honey samples and presence of colour as a consequence of added dye appear to be appropriate methods to follow honey adulteration, and further studies are ongoing.

  16. Review Essay: Governmentality in Late Colonial Korea?

    Directory of Open Access Journals (Sweden)

    Henry Em

    2012-12-01

    Full Text Available Takashi Fujitani, Race for Empire: Koreans as Japanese and Japanese as Americans during World War II. Berkeley: University of California Press, 2011. 520 pp. $65 (cloth.Jun Uchida, Brokers of Empire: Japanese Settler Colonialism in Korea, 1876-1945. Cambridge, MA: Harvard University Press, 2011. 500 pp. $50 (cloth.In South Korea, more so than in most other postcolonial countries, the issue of sovereignty and the colonial past remains a central feature of politics. Most recently, during a televised presidential debate on December 4, 2012, Lee Jung-hee of the Unified Progressive Party said something that likely had never been said on South Korean television: “Takaki Masao signed an oath of loyalty [to the Emperor of Japan], in his own blood, to become an officer in the Japanese [Imperial] Army. You know who he is. His Korean name is Park Chung Hee.” Lee Jung-hee then made the connection between that colonial past and the willingness to sell out the nation’s sovereignty in the present. The conservative candidate Park Geun-hye, the daughter of the late President Park Chung Hee who ruled South Korea from 1961 through 1979, and members of Park’s Saenuri Party, remain true to their “roots”: these “descendants of pro-Japanese collaborators and dictators” (again sold out South Korea’s sovereignty (on November 22, 2011 when they rammed the US-ROK Free Trade Agreement through the National Assembly.

  17. Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor

    DEFF Research Database (Denmark)

    Hess, David A; Bonde, Jesper; Craft, Timothy P

    2007-01-01

    ) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells....... The frequencies of NOD/SCID repopulating cells (SRC) were 1 SRC in 8.7 x 10(6) AMD3100-mobilized MNC compared to 1 SRC in 29.0 x 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 x 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation...

  18. Dynamics of the Presence of Israeli Acute Paralysis Virus in Honey Bee Colonies with Colony Collapse Disorder

    OpenAIRE

    Chunsheng Hou; Hadassah Rivkin; Yossi Slabezki; Nor Chejanovsky

    2014-01-01

    The determinants of Colony Collapse Disorder (CCD), a particular case of collapse of honey bee colonies, are still unresolved. Viruses including the Israeli acute paralysis virus (IAPV) were associated with CCD. We found an apiary with colonies showing typical CCD characteristics that bore high loads of IAPV, recovered some colonies from collapse and tested the hypothesis if IAPV was actively replicating in them and infectious to healthy bees. We found that IAPV was the dominant pathogen and ...

  19. Physical Forces Modulate Oxidative Status and Stress Defense Meditated Metabolic Adaptation of Yeast Colonies: Spaceflight and Microgravity Simulations

    Science.gov (United States)

    Hammond, Timothy G.; Allen, Patricia L.; Gunter, Margaret A.; Chiang, Jennifer; Giaever, Guri; Nislow, Corey; Birdsall, Holly H.

    2017-12-01

    Baker's yeast (Saccharomyces cerevisiae) has broad genetic homology to human cells. Although typically grown as 1-2mm diameter colonies under certain conditions yeast can form very large (10 + mm in diameter) or `giant' colonies on agar. Giant yeast colonies have been used to study diverse biomedical processes such as cell survival, aging, and the response to cancer pharmacogenomics. Such colonies evolve dynamically into complex stratified structures that respond differentially to environmental cues. Ammonia production, gravity driven ammonia convection, and shear defense responses are key differentiation signals for cell death and reactive oxygen system pathways in these colonies. The response to these signals can be modulated by experimental interventions such as agar composition, gene deletion and application of pharmaceuticals. In this study we used physical factors including colony rotation and microgravity to modify ammonia convection and shear stress as environmental cues and observed differences in the responses of both ammonia dependent and stress response dependent pathways We found that the effects of random positioning are distinct from rotation. Furthermore, both true and simulated microgravity exacerbated both cellular redox responses and apoptosis. These changes were largely shear-response dependent but each model had a unique response signature as measured by shear stress genes and the promoter set which regulates them These physical techniques permitted a graded manipulation of both convection and ammonia signaling and are primed to substantially contribute to our understanding of the mechanisms of drug action, cell aging, and colony differentiation.

  20. Rapid behavioral maturation accelerates failure of stressed honey bee colonies

    Science.gov (United States)

    Perry, Clint J.; Myerscough, Mary R.; Barron, Andrew B.

    2015-01-01

    Many complex factors have been linked to the recent marked increase in honey bee colony failure, including pests and pathogens, agrochemicals, and nutritional stressors. It remains unclear, however, why colonies frequently react to stressors by losing almost their entire adult bee population in a short time, resulting in a colony population collapse. Here we examine the social dynamics underlying such dramatic colony failure. Bees respond to many stressors by foraging earlier in life. We manipulated the demography of experimental colonies to induce precocious foraging in bees and used radio tag tracking to examine the consequences of precocious foraging for their performance. Precocious foragers completed far fewer foraging trips in their life, and had a higher risk of death in their first flights. We constructed a demographic model to explore how this individual reaction of bees to stress might impact colony performance. In the model, when forager death rates were chronically elevated, an increasingly younger forager force caused a positive feedback that dramatically accelerated terminal population decline in the colony. This resulted in a breakdown in division of labor and loss of the adult population, leaving only brood, food, and few adults in the hive. This study explains the social processes that drive rapid depopulation of a colony, and we explore possible strategies to prevent colony failure. Understanding the process of colony failure helps identify the most effective strategies to improve colony resilience. PMID:25675508

  1. Engaging With Colonial Archives: Reflections Of An End-User

    Directory of Open Access Journals (Sweden)

    Ayodeji Olukoju

    2016-06-01

    Full Text Available Official and/or public archives were a byproduct of colonial rule in Africa. (Archives are a byproduct of administrative governance everywhere. Given the density and diversity of colonial archival records, historians have tended to rely on them for the study of the colonial period. Publications on the use of archives have not captured the perspective of end-users, who often face peculiar challenges in the use of colonial and metropolitan archives. This paper provides an end-user perspective on colonial archives in Nigeria and the United Kingdom. It highlights the challenges of data collection and prospects of optimal use of archival source material. The discussion is of general application to users of colonial archives especially in the former British colonies in Africa.

  2. Termites: a Retinex implementation based on a colony of agents

    Science.gov (United States)

    Simone, Gabriele; Audino, Giuseppe; Farup, Ivar; Rizzi, Alessandro

    2012-01-01

    This paper describes a novel implementation of the Retinex algorithm with the exploration of the image done by an ant swarm. In this case the purpose of the ant colony is not the optimization of some constraints but is an alternative way to explore the image content as diffused as possible, with the possibility of tuning the exploration parameters to the image content trying to better approach the Human Visual System behavior. For this reason, we used "termites", instead of ants, to underline the idea of the eager exploration of the image. The paper presents the spatial characteristics of locality and discusses differences in path exploration with other Retinex implementations. Furthermore a psychophysical experiment has been carried out on eight images with 20 observers and results indicate that a termite swarm should investigate a particular region of an image to find the local reference white.

  3. Intraspecific Variation among Social Insect Colonies: Persistent Regional and Colony-Level Differences in Fire Ant Foraging Behavior.

    Directory of Open Access Journals (Sweden)

    Alison A Bockoven

    Full Text Available Individuals vary within a species in many ecologically important ways, but the causes and consequences of such variation are often poorly understood. Foraging behavior is among the most profitable and risky activities in which organisms engage and is expected to be under strong selection. Among social insects there is evidence that within-colony variation in traits such as foraging behavior can increase colony fitness, but variation between colonies and the potential consequences of such variation are poorly documented. In this study, we tested natural populations of the red imported fire ant, Solenopsis invicta, for the existence of colony and regional variation in foraging behavior and tested the persistence of this variation over time and across foraging habitats. We also reared single-lineage colonies in standardized environments to explore the contribution of colony lineage. Fire ants from natural populations exhibited significant and persistent colony and regional-level variation in foraging behaviors such as extra-nest activity, exploration, and discovery of and recruitment to resources. Moreover, colony-level variation in extra-nest activity was significantly correlated with colony growth, suggesting that this variation has fitness consequences. Lineage of the colony had a significant effect on extra-nest activity and exploratory activity and explained approximately half of the variation observed in foraging behaviors, suggesting a heritable component to colony-level variation in behavior.

  4. Criteria for feasibility, health and welfare assessment of requirement to use second and subsequent generations of non-human primates or animals from self-sustaining colonies in research Critères d’évaluation de la faisabilité, de l’incidence sanitaire et des répercussions sur le bien-être animal, relatifs à l'obligation future d'utiliser des primates non humains issus uniquement des animaux de deuxième génération et plus ou des animaux provenant de colonies d'élevage auto-entretenues pour la recherche expérimentale

    Directory of Open Access Journals (Sweden)

    David Smith

    2011-10-01

    Full Text Available The European Directive 2010/63/EU on the protection of animals used for scientific purposes requires that a feasibility study must be conducted by the European Commission to determine if all sourcing of non-human primates from parents bred in captivity (F2 or from self-sustaining colonies can be achieved. This study should also include an assessment of animal health and welfare. Prior to the initiation of the European Commission’s study, it was considered by EFPIA and FELASA that the criteria to be used in the feasibility, health and welfare assessment should be established by experts to help expedite such a study. This paper identifies those criteria which may be useful in making policy decisions on the confirmation or reconsideration of the timetable for implementation of the F2 requirement. A key requirement before a number of criteria can be assessed is the generation of base-line data relating to the supply and future demand of non-human primates and the health and welfare status of current breeding colonies supplying the European market. Three groups of criteria have been indentified, namely feasibility, science and research and welfare. Within each group, a number of parameters are defined and their rationale for inclusion, together with suggested information points, is discussed.La directive européenne 2010/63/EU sur la protection des animaux utilisés à des fins scientifiques exige qu'une étude de faisabilité soit conduite par la Commission européenne afin de déterminer si l’approvisionnement en primates non-humains à partir de géniteurs élevés en captivité (F2 ou de colonies d'élevage autosuffisantes, peut être possible. Cette étude devra également inclure une évaluation de la santé des animaux et de leur bien-être. Avant le début de cette étude par la Commission européenne, l'EFPIA et FELASA ont estimé que les critères à utiliser pour les évaluations de la faisabilité, de la santé des animaux et du bien

  5. Globalization in the post - colonial world

    Directory of Open Access Journals (Sweden)

    Korobeynikova Larisa A.

    2016-01-01

    Full Text Available The paper presents a new interpretation of globalization within the boundaries of the author’s concept of soft globalization, which exploits a normatively attractive alternative to the concept of the Empire. It is argued here that the conditions of development of contemporary post - colonial world communities do not require any unification in the form of the Empire, but instead the creation of a non repressive mechanism of social regulation - the implementation of a form of soft globalization, a globalization with a mental form are expedient here. Historically, globalization occurred in a strict material(i.e. economical and military form that prompted the conditions for the evolution of civilization as the Empire: a case in which the development of the world occurs under the power of a single dominating state. Imperialistic politics leads to colonial politics formation. The history of the phenomena of civilization shows many instances of Empire globalization. Globalization in the Empire form was already observed at the time of the Roman Empire. At this time processes of development inside the Empire were manifestations of globalization in its highest cultural shape. But ancient Rome was also a social and political experiment that acquired the attributes of a purely material globalization in the end, and historically brought about the irreversible crash of the Roman Empire itself. Contemporary fluctuations referring to the process of globalization can be registered in the US’s attempts of material domination inside this or that existing case of civilization, which causes colonialism appearance. The main idea stressed in the paper is that only a mental globalization could succeed in the end.

  6. Bodies for empire: biopolitics, reproduction, and sexual knowledge in late colonial Korea.

    Science.gov (United States)

    Park, Jin-kyung

    2014-08-01

    actively sought to mobilize Koreans as crucial human resources for the further penetration of Japan's imperial holdings into the Chinese continent. State and non-state medical doctors meticulously interrogated, recorded, and circulated knowledge about the sexual and conjugal practices and reproductive life of Korean women in the agricultural sector, for the purposes of measuring and increasing the size, health, and vitality of the colonial population. At the heart of such medical endeavors stood the Investigative Committee for Social Hygiene in Rural Korea and Japan-trained Korean medical students/physicians, including Chóe Ŭg-sŏk, who carried out a social hygiene study in the mid-1930s. Their study illuminates the ways in which Korean women's bodies entered the modern domain of scientific knowledge at the intersection of Japan's imperialism, colonial governmentality, and biomedicine. A critical case study of the Investigative Committee's study and Chóe can set the stage for clarifying the vestiges as well as the reformulation of knowledge, ideas, institutions, and activities of colonial biopolitics in the divided Koreas.

  7. Colonial Subjectification: Foucault, Christianity and Governmentality

    Directory of Open Access Journals (Sweden)

    Christina Petterson

    2012-09-01

    Full Text Available Foucault’s concept of pastoral power is envisioned as a technique of power developed from the medieval period and carried through into modern political rationalities. As such, it is an old power technique – which originated in Christian institutions – in a new political shape, which he coined governmentality. This article uses Foucault’s genealogy of pastoral power and governmentality to discuss the intersection of domination and technology of self in the Greenlandic colonial context and to bring out the central role of religion in Foucault’s conceptualisation of governmentality.

  8. Studying Colonialism in Spanish History Textbooks

    DEFF Research Database (Denmark)

    Brescó, Ignacio

    2017-01-01

    The interwoven dynamics underpinning national identity and collective memory have received growing interest from different disciplines in light of an increasingly globalized and multicultural world. In this context, history textbooks play an important role inasmuch as the introduction of history...... in Africa and when Spain was going through a transition process towards democracy), and the current period (Spain being a consolidated democracy and a growing multicultural society). In this historical comparative analysis the focus will be, beside on colonialism in general from mid-19th century until...

  9. Combined Final Report for Colony II Project

    Energy Technology Data Exchange (ETDEWEB)

    Kale, Laxmikant [University of Illinois; Jones, Terry [Oak Ridge National Laboratory; Moreira, Jose [IBM Corp.

    2013-10-23

    (This report was originally submmited by the lead PI (Terry Jones, ORNL) on October 22, 2013 to the program manager, Lucy Nowell. It is being submitted from University of Illinois in accordance with instructions). HPC Colony II seeks to provide portable performance for leadership class machines. Our strategy is based on adaptive system software that aims to make the intelligent decisions necessary to allow domain scientists to safely focus on their task at hand and allow the system software stack to adapt their application to the underlying architecture. This report describes the research undertaken towards these objectives and the results obtained over the performance period of the project.

  10. Apuntes sobre el urbanismo en Brasil colonial

    Directory of Open Access Journals (Sweden)

    Luisa Durán Rocca

    2009-07-01

    Full Text Available El texto que el lector tiene en sus manos pretende hacer una síntesis del proceso de formación del espacio urbano colonial brasilero, ilustrando el trayecto de una práctica espacial de más de tres siglos, derivada de la milenaria tradición urbana portuguesa. A partir del reconocimiento de la dimensión histórico-artística de la arquitectura y los hechos urbanos2, se asume la indisolubilidad entre la sociedad y el espacio que ésta produce y se conceptúa la urbanización como un proceso social.

  11. Stages of Colonialism in Africa: From Occupation of Land to Occupation of Being

    Directory of Open Access Journals (Sweden)

    Hussein A. Bulhan

    2015-08-01

    Full Text Available This paper draws primarily on my own scholarship, supplemented by the limited academic resources available in the “peripheries” of the world where I live and work (namely, Somali society and Darfur, Sudan, to consider the relationship between colonialism and psychology. I first consider the history of psychology in justifying and bolstering oppression and colonialism. I then consider the ongoing intersection of colonialism and psychology in the form of metacolonialism (or coloniality. I end with thoughts about decolonizing psychological science in teaching, social, and clinical practice. To decolonize psychological science, it is necessary to transform its focus from promotion of individual happiness to cultivation of collective well-being, from a concern with instinct to promotion of human needs, from prescriptions for adjustment to affordances for empowerment, from treatment of passive victims to creation of self-determining actors, and from globalizing, top-down approaches to context-sensitive, bottom-up approaches. Only then will the field realize its potential to advance Frantz Fanon’s call for humane and just social order.

  12. Humane Education: An Overview.

    Science.gov (United States)

    Whitlock, Eileen S.; Westerlund, Stuart R.

    This booklet traces the historical development of human education as it has been instilled into the young people of America from colonial times to the present and provides a future prognosis of humaneness in the schools. Humane education promotes humane behavior and is an important part of the humane movement in the United States, although until…

  13. a Missing Link? - Mesoscale Distributions of Colonial Phaeocystis Antarctica and its Ghost Colonies in the Ross Sea

    Science.gov (United States)

    Smith, W.; McGillicuddy, D. J., Jr.; Olson, E.; Sosik, H. M.; Peacock, E.

    2016-02-01

    It is well established that the haptophyte Phaeocystis antarctica is a dominant member of the Ross Sea phytoplankton, contributing more than half of the annual production. Its broad spatial distribution has been documented by ship sampling, but its mesoscale variations are poorly known. In the PRISM (Processes Regulating Iron Supply at the Mesoscale) project in 2011, we deployed a Video Plankton Recorder (VPR) for 24 h between selected locations that had been identified by satellite images to have eddy-like features. As P. antarctica colonies are far larger than the VPR's camera resolution (2 mm vs. 40 µm), we were able to quantify colonial contributions to total fluorescence and particulate organic carbon, resolving distances of a few kms and depths of ca. 1 m. Within these surveys, we found unusual forms of colonies, which we subsequently deemed "ghost colonies"; that is, colonies that have largely lost their cells and have collapsed. While ghost colonies generally were located deeper in the water column than intact colonies, not all surface Phaeocystis blooms were associated with ghost colonies. For example, in one survey ghost colonies and intact colonial forms were present throughout the water column, but with distributions separated by depth; while in another survey, their distributions appeared to be spatially distinct in the horizontal. We hypothesize that ghost colonies are formed upon extreme micronutrient stress, which causes colonies to sink and cells to be liberated from colonies. Considerable mesoscale variability was noted in P. antarctica distributions and was related to oceanographic features. The mesoscale variations in both P. antarctica and its ghost colonies potentially have significant impacts on vertical fluxes and biogeochemical cycles in the Ross Sea.

  14. CHRISTIANITY AND COLONIALISM IN SOME ENGLISH SHORT STORIES

    Directory of Open Access Journals (Sweden)

    Tatang Iskarna

    2017-04-01

    Full Text Available Colonial and postcolonial studies are often linked to the power domination of the West upon the East in the way that the East economically, politically, and socially oppressed. Colonialism is often associated with three elements, the explorers dealing with geographical information, missionaries approaching the local people culturally, and the colonial administrators ruling the colony. Gold, glory, and gospel are the European’s concern. However, in representing the relation between Christianity and colonialism there is critical dialectic amongst historians, anthropologists, Christian missions, or cultural critics. Some propose that Christianity is considered to be the religious arm of colonialism. Others state that Christianity is spread without any secular interest as it is a great commandment of Jesus Christ. A few believe that Christianity give critical resistance against colonialism. The relation between Christianity and colonialism cannot be simplified as being neutral, in complicity, or in opposition. So, it is worth-discussing to understand how European writers construct the relation between Christianity and colonialism in their literary work. How Christianity is constructed and how Christianity is related to colonialism will be discussed in this paper. Using postcolonial paradigm, two English short stories will be analyzed in that way. They are Rudyard Kipling’s “Lispeth” and Doris Lessing’s “No Witchcraft for Sale”.

  15. Colony age, neighborhood density and reproductive potential in harvester ants.

    Science.gov (United States)

    Wagner, Diane; Gordon, Deborah M

    1999-05-01

    At about age 5 years, colonies of the harvester ant, Pogonomyrmex barbatus, begin to produce winged, sexual forms (alates) that mate in large annual aggregations. We examined how colony age and neighborhood density affect the numbers, body mass, and body fat of alates produced by 172 colonies ranging in age from 4 to 17 years. Over one-third (36%) of all colonies produced no alates. Failure to reproduce was independent of colony age. Of those colonies that did produce alates, older colonies produced more alates than younger colonies. Older colonies produced lighter female alates (in dry mass), but the total biomass of additional alates produced by older colonies far outweighed the reduced allocation to female alate body mass. Body fat content was much higher in female alates (36.0% on average) than in males (3.7% on average). Alate body fat content was not related to colony age. The fitness of female alates may be related to their fresh body mass; that of females captured after mating and reared in the laboratory was positively correlated with egg-laying rate, although not with the total number of eggs in the first brood. Neighborhood density was not related to alate number, mass, or fat content, in contrast to the results of a 1995 study at the site, in which alate numbers were negatively related to neighborhood density. Thus the influence of crowding on reproductive output appears to vary from year to year, perhaps in response to variation in rainfall and food supply. Alate output by individual colonies was correlated among years. These results suggest that a few, older colonies dominate the pool of reproductives year after year.

  16. Effect of fluid motion on colony formation in Microcystis aeruginosa

    Directory of Open Access Journals (Sweden)

    Lin Li

    2013-01-01

    Full Text Available Microcystis aeruginosa, generally occurring in large colonies under natural conditions, mainly exists as single cells in laboratory cultures. The mechanisms involved in colony formation in Microcystis aeruginosa and their roles in algal blooms remain unknown. In this study, based on previous research findings that fluid motion may stimulate the colony formation in green algae, culture experiments were conducted under axenic conditions in a circular water chamber where the flow rate, temperature, light, and nutrients were controlled. The number of cells of Microcystis aeruginosa, the number of cells per colony, and the colonial characteristics in various growth phases were observed and measured. The results indicated that the colony formation in Microcystis aeruginosa, which was not observed under stagnant conditions, was evident when there was fluid motion, with the number of cells per largest colony reaching 120 and the proportion of the number of cells in colonial form to the total number of cells and the mean number of cells per colony reaching their peak values at a flow rate of 35 cm/s. Based on the analysis of colony formation process, fluid motion stimulates the colony formation in Microcystis aeruginosa in the lag growth phase, while flushes and disaggregates the colonies in the exponential growth phase. The stimulation effect in the lag growth phase may be attributable to the involvement of fluid motion in a series of physiological processes, including the uptake of trace elements and the synthesis and secretion of polysaccharides. In addition, the experimental groups exhibiting typical colonial characteristics in the lag growth phase were found to have higher cell biomass in the later phase.

  17. Persistent STAT5 phosphorylation and epigenetic dysregulation of GM-CSF and PGS2/COX2 expression in Type 1 diabetic human monocytes.

    Directory of Open Access Journals (Sweden)

    Erin Garrigan

    Full Text Available STAT5 proteins are adaptor proteins for histone acetylation enzymes. Histone acetylation at promoter and enhancer chromosomal regions opens the chromatin and allows access of transcription enzymes to specific genes in rapid response cell signals, such as in inflammation. Histone acetylation-mediated gene regulation is involved in expression of 2 key inflammatory response genes: CSF2, encoding granulocyte-macrophage colony stimulating factor (GM-CSF, and PTGS2, encoding prostaglandin synthase 2/cyclooxygenase 2 (PGS2/COX2. Prolonged CSF2 expression, high GM-CSF production, and GM-CSF activation of PTGS2 gene expression all are seen in type 1 diabetes (T1D monocytes. Persistent phosphorylation activation of monocyte STAT5 (STAT5Ptyr is also found in individuals with or at-risk for T1D. To examine whether elevated T1D monocyte STAT5Ptyr may be associated with aberrant inflammatory gene expression in T1D, blood monocytes from non-autoimmune controls and T1D patients were analyzed by flow cytometry for STAT5Ptyr activation, and by chromatin immuno-precipitation (ChIP analyses for STAT5Ptyr's ability to bind at CSF2 and PTGS2 regulatory sites in association with histone acetylation. In unstimulated monocytes, STAT5Ptyr was elevated in 59.65% of T1D, but only 2.44% of control subjects (p<0.0001. Increased STAT5Ptyr correlated with T1D disease duration (p = 0.0030, r(2 = 0.0784. Unstimulated (p = 0.140 and GM-CSF-stimulated (p = 0.0485 T1D monocytes, had greater STAT5Ptyr binding to epigenetic regulatory sites upstream of CSF2 than control monocytes. Increased STAT5Ptyr binding in T1D monocytes was concurrent with binding at these sites of STAT6Ptyr (p = 0.0283, CBP/P300 histone acetylase, acetylated histones H3, SMRT/NCoR histone deacetylase (p = 0.0040, and RNA Polymerase II (p = 0.0040. Our study indicates that in T1D monocytes, STAT5Ptyr activation is significantly higher and that STAT5Ptyr is found bound to CSF2 promoter and PTGS2 enhancer regions

  18. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Directory of Open Access Journals (Sweden)

    Ana Traven

    Full Text Available Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development

  19. Colonial Army Formats in Africa and Post-Colonial Military Coups:

    African Journals Online (AJOL)

    BSOS USER

    Since time immemorial, societies, states and state builders have been challenged and transformed by the need and quest for military manpower.1. European states relied on conscript armies to 'pacify' and retain colonies in parts of the non-European world. These facts underscore the meticulous attention paid by the British ...

  20. Designing communicating colonies of biomimetic microcapsules.

    Science.gov (United States)

    Kolmakov, German V; Yashin, Victor V; Levitan, Steven P; Balazs, Anna C

    2010-07-13

    Using computational modeling, we design colonies of biomimetic microcapsules that exploit chemical mechanisms to communicate and alter their local environment. As a result, these synthetic objects can self-organize into various autonomously moving structures and exhibit ant-like tracking behavior. In the simulations, signaling microcapsules release agonist particles, whereas target microcapsules release antagonist particles and the permeabilities of both capsule types depend on the local particle concentration in the surrounding solution. Additionally, the released nanoscopic particles can bind to the underlying substrate and thereby create adhesion gradients that propel the microcapsules to move. Hydrodynamic interactions and the feedback mechanism provided by the dissolved particles are both necessary to achieve the collective dynamics exhibited by these colonies. Our model provides a platform for integrating both the spatial and temporal behavior of assemblies of "artificial cells," and allows us to design a rich variety of structures capable of exhibiting complex, cooperative behavior. Due to the cell-like attributes of polymeric microcapsules and polymersomes, material systems are available for realizing our predictions.

  1. Physicians of colonial India (1757-1900

    Directory of Open Access Journals (Sweden)

    Anu Saini

    2016-01-01

    Full Text Available The period of British rule from 1757 to 1900 is marked by major sociopolitical changes and scientific breakthroughs that impacted medical systems, institutions, and practitioners in India. In addition, historians have debated whether the colonial regime used Western medicine as a tool to expand and legitimize its rule. This paper reviews the secondary literature on this subject with emphasis on the individual physicians. During this period, the practice of "Doctory" or Western medicine gained momentum in India, buoyed with the support of the British as well as Western-educated Indians. Many Indians were trained in Western medicine and employed by the administration as "native doctors" in the subordinate medical service, and the superior medical service by and large comprised Europeans. The colonial regime gradually withdrew most of its patronage to the indigenous systems of medicine. The practitioners of these systems, the vaidyas and the hakims, suffered significant loss of prestige against Western medicine′s claims of being a more rational "superior" system of medicine. Some of them became purists and defended and promoted their systems, while others adopted the methods and ideas of Western medicine into their education and practice. European doctors now rarely interacted with practitioners of Indian systems, but seriously pursued research into medicinal plants and tropical diseases. There is no mention of specialist physicians in this period, and all physicians and surgeons were generalists. Folk practitioners continued to be popular among the masses.

  2. First recorded loss of an emperor penguin colony in the recent period of Antarctic regional warming: implications for other colonies.

    Directory of Open Access Journals (Sweden)

    Philip N Trathan

    Full Text Available In 1948, a small colony of emperor penguins Aptenodytes forsteri was discovered breeding on Emperor Island (67° 51' 52″ S, 68° 42' 20″ W, in the Dion Islands, close to the West Antarctic Peninsula (Stonehouse 1952. When discovered, the colony comprised approximately 150 breeding pairs; these numbers were maintained until 1970, after which time the colony showed a continuous decline. By 1999 there were fewer than 20 pairs, and in 2009 high-resolution aerial photography revealed no remaining trace of the colony. Here we relate the decline and loss of the Emperor Island colony to a well-documented rise in local mean annual air temperature and coincident decline in seasonal sea ice duration. The loss of this colony provides empirical support for recent studies (Barbraud & Weimerskirch 2001; Jenouvrier et al 2005, 2009; Ainley et al 2010; Barber-Meyer et al 2005 that have highlighted the vulnerability of emperor penguins to changes in sea ice duration and distribution. These studies suggest that continued climate change is likely to impact upon future breeding success and colony viability for this species. Furthermore, a recent circumpolar study by Fretwell & Trathan (2009 highlighted those Antarctic coastal regions where colonies appear most vulnerable to such changes. Here we examine which other colonies might be at risk, discussing various ecological factors, some previously unexplored, that may also contribute to future declines. The implications of this are important for future modelling work and for understanding which colonies actually are most vulnerable.

  3. First recorded loss of an emperor penguin colony in the recent period of Antarctic regional warming: implications for other colonies.

    Science.gov (United States)

    Trathan, Philip N; Fretwell, Peter T; Stonehouse, Bernard

    2011-02-28

    In 1948, a small colony of emperor penguins Aptenodytes forsteri was discovered breeding on Emperor Island (67° 51' 52″ S, 68° 42' 20″ W), in the Dion Islands, close to the West Antarctic Peninsula (Stonehouse 1952). When discovered, the colony comprised approximately 150 breeding pairs; these numbers were maintained until 1970, after which time the colony showed a continuous decline. By 1999 there were fewer than 20 pairs, and in 2009 high-resolution aerial photography revealed no remaining trace of the colony. Here we relate the decline and loss of the Emperor Island colony to a well-documented rise in local mean annual air temperature and coincident decline in seasonal sea ice duration. The loss of this colony provides empirical support for recent studies (Barbraud & Weimerskirch 2001; Jenouvrier et al 2005, 2009; Ainley et al 2010; Barber-Meyer et al 2005) that have highlighted the vulnerability of emperor penguins to changes in sea ice duration and distribution. These studies suggest that continued climate change is likely to impact upon future breeding success and colony viability for this species. Furthermore, a recent circumpolar study by Fretwell & Trathan (2009) highlighted those Antarctic coastal regions where colonies appear most vulnerable to such changes. Here we examine which other colonies might be at risk, discussing various ecological factors, some previously unexplored, that may also contribute to future declines. The implications of this are important for future modelling work and for understanding which colonies actually are most vulnerable.

  4. The relevance of the Mediterranean Region to colonial waterbird conservation

    Science.gov (United States)

    Erwin, R.M.; Crivelli, Alain J.; Hafner, Heinz; Fasola, Mauro; Erwin, R. Michael; McCrimmon, Donald A.=

    1996-01-01

    The Mediterranean Sea is the largest partially enclosed sea in the world and provides habitat to more than 100 species of waterbirds from the Palearctic-North African-Middle Eastern regions. Even though the Mediterranean suffers from pollution, has little tidal influence, and is oligotrophic, more than half of the western Palearctic populations of numerous waterfowl species winter in the region. Thirty-three species of colonial waterbirds breed along the 46,000 km Mediterranean coastline with nine species considered threatened or endangered, mostly because of wetland loss and degradation. The long history of human activity and scientific investigations in the region has taught some valuable lessons. In the area of colonial waterbird biology and conservation, we have learned important lessons about the value of long-term monitoring and research on selected populations. From marking studies of Greater Flamingos (Phoenicopterus ruber roseus) and Little Egrets (Egretta garzetta) results have been used to derive useful information about metapopulation dynamics. Involvement of both African and European biologists allowed year-round Studies of these species that yielded valuable spin-offs for training in avian and wetland conservation. We have also learned the value of man-made wetlands as feeding and nesting sites for some colonial waterbirds. Careful evaluations of the habitat quality of different types of wetlands are required, as in contaminant levels such as lead shot and pesticides. Wetland conservationists have also learned from some instructive mistakes. Dam construction and agricultural incentive programs sponsored by the European Community, the World Bank, and others from the past have largely ignored impacts on wetlands and wildlife. In some areas, economic ventures such as aquaculture operations and salt mining have not involved waterbird habitat needs in their planning. Research and conservation needs include: (1) establishing regional monitoring programs and

  5. Cocktail-party effect in king penguin colonies

    OpenAIRE

    T. Aubin; Jouventin, P.

    1998-01-01

    The king penguin, Aptenodytes patagonicus, breeds without a nest in colonies of several thousands of birds. To be fed, the chick must recognize the parents in a particularly noisy environment using only vocal cues. The call an adult makes when seeking the chick is emitted at a high amplitude level. Nevertheless, it is transmitted in a colonial context involving the noise generated by the colony and the screening effect of the bodies, both factors reducing the signal-to-noise ratio. In additio...

  6. Colony patterning and collective hyphal growth of filamentous fungi

    Science.gov (United States)

    Matsuura, Shu

    2002-11-01

    Colony morphology of wild and mutant strains of Aspergillus nidulans at various nutrient and agar levels was investigated. Two types of colony patterning were found for these strains. One type produced uniform colonies at all nutrient and agar levels tested, and the other exhibited morphological change into disordered ramified colonies at low nutrient levels. Both types showed highly condensed compact colonies at high nutrient levels on low agar media that was highly diffusive. Disordered colonies were found to develop with low hyphal extension rates at low nutrient levels. To understand basic pattern selection rules, a colony model with three parameters, i.e., the initial nutrient level and the step length of nutrient random walk as the external parameters, and the frequency of nutrient uptake as an internal parameter, was constructed. At low nutrient levels, with decreasing nutrient uptake frequency under diffusive conditions, the model colony exhibited onsets of disordered ramification. Further, in the growth process of A. nidulans, reduction of hyphal extension rate due to a population effect of hyphae was found when hyphae form three-dimensional dense colonies, as compared to the case in which hyphal growth was restricted into two-dimensional space. A hyphal population effect was introduced in the colony model. Thickening of colony periphery due to the population effect became distinctive as the nutrient diffusion effect was raised at high nutrient levels with low hyphal growth rate. It was considered that colony patterning and onset of disorder were strongly governed by the combination of nutrient diffusion and hyphal growth rate.

  7. Neonicotinoid pesticides can reduce honeybee colony genetic diversity

    Science.gov (United States)

    Troxler, Aline; Retschnig, Gina; Gauthier, Laurent; Straub, Lars; Moritz, Robin F. A.; Neumann, Peter; Williams, Geoffrey R.

    2017-01-01

    Neonicotinoid insecticides can cause a variety of adverse sub-lethal effects in bees. In social species such as the honeybee, Apis mellifera, queens are essential for reproduction and colony functioning. Therefore, any negative effect of these agricultural chemicals on the mating success of queens may have serious consequences for the fitness of the entire colony. Queens were exposed to the common neonicotinoid pesticides thiamethoxam and clothianidin during their developmental stage. After mating, their spermathecae were dissected to count the number of stored spermatozoa. Furthermore, their worker offspring were genotyped with DNA microsatellites to determine the number of matings and the genotypic composition of the colony. Colonies providing the male mating partners were also inferred. Both neonicotinoid and control queens mated with drones originating from the same drone source colonies, and stored similar number of spermatozoa. However, queens reared in colonies exposed to both neonicotinoids experienced fewer matings. This resulted in a reduction of the genetic diversity in their colonies (i.e. higher intracolonial relatedness). As decreased genetic diversity among worker bees is known to negatively affect colony vitality, neonicotinoids may have a cryptic effect on colony health by reducing the mating frequency of queens. PMID:29059234

  8. Improved Ant Colony Clustering Algorithm and Its Performance Study

    Directory of Open Access Journals (Sweden)

    Wei Gao

    2016-01-01

    Full Text Available Clustering analysis is used in many disciplines and applications; it is an important tool that descriptively identifies homogeneous groups of objects based on attribute values. The ant colony clustering algorithm is a swarm-intelligent method used for clustering problems that is inspired by the behavior of ant colonies that cluster their corpses and sort their larvae. A new abstraction ant colony clustering algorithm using a data combination mechanism is proposed to improve the computational efficiency and accuracy of the ant colony clustering algorithm. The abstraction ant colony clustering algorithm is used to cluster benchmark problems, and its performance is compared with the ant colony clustering algorithm and other methods used in existing literature. Based on similar computational difficulties and complexities, the results show that the abstraction ant colony clustering algorithm produces results that are not only more accurate but also more efficiently determined than the ant colony clustering algorithm and the other methods. Thus, the abstraction ant colony clustering algorithm can be used for efficient multivariate data clustering.

  9. Varroa-virus interaction in collapsing honey bee colonies.

    Directory of Open Access Journals (Sweden)

    Roy M Francis

    Full Text Available Varroa mites and viruses are the currently the high-profile suspects in collapsing bee colonies. Therefore, seasonal variation in varroa load and viruses (Acute-Kashmir-Israeli complex (AKI and Deformed Wing Virus (DWV were monitored in a year-long study. We investigated the viral titres in honey bees and varroa mites from 23 colonies (15 apiaries under three treatment conditions: Organic acids (11 colonies, pyrethroid (9 colonies and untreated (3 colonies. Approximately 200 bees were sampled every month from April 2011 to October 2011, and April 2012. The 200 bees were split to 10 subsamples of 20 bees and analysed separately, which allows us to determine the prevalence of virus-infected bees. The treatment efficacy was often low for both treatments. In colonies where varroa treatment reduced the mite load, colonies overwintered successfully, allowing the mites and viruses to be carried over with the bees into the next season. In general, AKI and DWV titres did not show any notable response to the treatment and steadily increased over the season from April to October. In the untreated control group, titres increased most dramatically. Viral copies were correlated to number of varroa mites. Most colonies that collapsed over the winter had significantly higher AKI and DWV titres in October compared to survivors. Only treated colonies survived the winter. We discuss our results in relation to the varroa-virus model developed by Stephen Martin.

  10. Improved Ant Colony Clustering Algorithm and Its Performance Study.

    Science.gov (United States)

    Gao, Wei

    2016-01-01

    Clustering analysis is used in many disciplines and applications; it is an important tool that descriptively identifies homogeneous groups of objects based on attribute values. The ant colony clustering algorithm is a swarm-intelligent method used for clustering problems that is inspired by the behavior of ant colonies that cluster their corpses and sort their larvae. A new abstraction ant colony clustering algorithm using a data combination mechanism is proposed to improve the computational efficiency and accuracy of the ant colony clustering algorithm. The abstraction ant colony clustering algorithm is used to cluster benchmark problems, and its performance is compared with the ant colony clustering algorithm and other methods used in existing literature. Based on similar computational difficulties and complexities, the results show that the abstraction ant colony clustering algorithm produces results that are not only more accurate but also more efficiently determined than the ant colony clustering algorithm and the other methods. Thus, the abstraction ant colony clustering algorithm can be used for efficient multivariate data clustering.

  11. Ant- and Ant-Colony-Inspired ALife Visual Art.

    Science.gov (United States)

    Greenfield, Gary; Machado, Penousal

    2015-01-01

    Ant- and ant-colony-inspired ALife art is characterized by the artistic exploration of the emerging collective behavior of computational agents, developed using ants as a metaphor. We present a chronology that documents the emergence and history of such visual art, contextualize ant- and ant-colony-inspired art within generative art practices, and consider how it relates to other ALife art. We survey many of the algorithms that artists have used in this genre, address some of their aims, and explore the relationships between ant- and ant-colony-inspired art and research on ant and ant colony behavior.

  12. La “Coppa Italia” delle Colonie Libere in Svizzera

    OpenAIRE

    Ricciardi, Toni

    2016-01-01

    On June 25, 1961, at the municipal stadium “Kleine Allmend” in Frauenfeld, the final of the first edition of the Italian Cup (Coppa Italia) – organized by the Federazione delle Colonie Libere Italiane in Svizzera – was played. The Colonie Libere represents an unicum – an exception – within the long and widespread tradition of migrant associationism. The first Colony arose from the mid-1920s thanks to the work of those who flee from fascism; after 1943 more than a hundred Colonies were opened ...

  13. Modeling man: the monkey colony at the Carnegie Institution of Washington's Department of Embryology, 1925-1971.

    Science.gov (United States)

    Wilson, Emily K

    2012-01-01

    Though better recognized for its immediate endeavors in human embryo research, the Carnegie Department of Embryology also employed a breeding colony of rhesus macaques for the purposes of studying human reproduction. This essay follows the course of the first enterprise in maintaining a primate colony for laboratory research and the overlapping scientific, social, and political circumstances that tolerated and cultivated the colony's continued operation from 1925 until 1971. Despite a new-found priority for reproductive sciences in the United States, by the early 1920s an unfertilized human ovum had not yet been seen and even the timing of ovulation remained unresolved. Progress would require an organized research approach that could extend beyond the limitations of working with scant and inherently restrictive human subjects or with common lab mammals like mice. In response, the Department of Embryology, under the Carnegie Institution of Washington (CIW), instituted a novel methodology using a particular primate species as a surrogate in studying normal human reproductive physiology. Over more than 40 years the monkey colony followed an unpremeditated trajectory that would contribute fundamentally to discoveries in human reproduction, early embryo development, reliable birth control methods, and to the establishment of the rhesus macaque as a common model organism.

  14. Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy.

    Science.gov (United States)

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H; Nørregaard, Rikke; Møller-Jensen, Jakob; Nejsum, Lene N

    2017-08-01

    To target bacterial pathogens that invade and proliferate inside host cells, it is necessary to design intervention strategies directed against bacterial attachment, cellular invasion and intracellular proliferation. We present an automated microscopy-based, fast, high-throughput method for analyzing size and number of intracellular bacterial colonies in infected tissue culture cells. Cells are seeded in 48-well plates and infected with a GFP-expressing bacterial pathogen. Following gentamicin treatment to remove extracellular pathogens, cells are fixed and cell nuclei stained. This is followed by automated microscopy and subsequent semi-automated spot detection to determine the number of intracellular bacterial colonies, their size distribution, and the average number per host cell. Multiple 48-well plates can be processed sequentially and the procedure can be completed in one working day. As a model we quantified intracellular bacterial colonies formed by uropathogenic Escherichia coli (UPEC) during infection of human kidney cells (HKC-8). Urinary tract infections caused by UPEC are among the most common bacterial infectious diseases in humans. UPEC can colonize tissues of the urinary tract and is responsible for acute, chronic, and recurrent infections. In the bladder, UPEC can form intracellular quiescent reservoirs, thought to be responsible for recurrent infections. In the kidney, UPEC can colonize renal epithelial cells and pass to the blood stream, either via epithelial cell disruption or transcellular passage, to cause sepsis. Intracellular colonies are known to be clonal, originating from single invading UPEC. In our experimental setup, we found UPEC CFT073 intracellular bacterial colonies to be heterogeneous in size and present in nearly one third of the HKC-8 cells. This high-throughput experimental format substantially reduces experimental time and enables fast screening of the intracellular bacterial load and cellular distribution of multiple

  15. New data on Weddell seal (Leptonychotes weddellii) colonies: A genetic analysis of a top predator from the Ross Sea, Antarctica.

    Science.gov (United States)

    Zappes, Ighor Antunes; Fabiani, Anna; Sbordoni, Valerio; Rakaj, Arnold; Palozzi, Roberto; Allegrucci, Giuliana

    2017-01-01

    In this paper, we studied the genetic variability in Weddell seal from colonies in Terra Nova Bay and Wood Bay, both sites located in the Ross Sea area, Antarctica. Two mitochondrial genes and one nuclear gene, with different mutation rates, were sequenced to investigate the haplotype diversity of the colonies and to test for a possible recent expansion. Fifteen microsatellites were used to analyze their genetic structure. Sequenced genes and microsatellites were also used to estimate the effective population size of the studied colonies and the Ross Sea seal population. The Ross Sea has a high density population of Weddel seals, with an estimated effective number of 50,000 females, and 1,341 individuals for the sampling area, possibly due to its high primary production. The colonies showed high diversity (Hd > 0.90) and many exclusive haplotypes (> 75%), likely a consequence of the surprisingly high site fidelity of Weddell seals, despite the proximity of the colonies. Nevertheless, there was low microsatellite differentiation between colonies, suggesting that they are part of a single larger population. Their expansion seemed to have started during the last glacial cycle (around 58,000 years ago), indicating that the Ross Sea seal populations have been present in the area for long time, probably due to the lack of hunting by humans and terrestrial predation. As a top predator, the role of Weddell seals in the Ross Sea ecology is crucial, and its demographic dynamics should be monitored to follow the future changes of such an important ecosystem.

  16. Metal contaminant accumulation in the hive: Consequences for whole-colony health and brood production in the honey bee (Apis mellifera L.).

    Science.gov (United States)

    Hladun, Kristen R; Di, Ning; Liu, Tong-Xian; Trumble, John T

    2016-02-01

    Metal pollution has been increasing rapidly over the past century, and at the same time, the human population has continued to rise and produce contaminants that may negatively impact pollinators. Honey bees (Apis mellifera L.) forage over large areas and can collect contaminants from the environment. The primary objective of the present study was to determine whether the metal contaminants cadmium (Cd), copper (Cu), lead (Pb), and selenium (Se) can have a detrimental effect on whole-colony health in the managed pollinator A. mellifera. The authors isolated small nucleus colonies under large cages and fed them an exclusive diet of sugar syrup and pollen patty spiked with Cd, Cu, Pb, and Se or a control (no additional metal). Treatment levels were based on concentrations in honey and pollen from contaminated hives around the world. They measured whole-colony health including wax, honey, and brood production; colony weight; brood survival; and metal accumulation in various life stages. Colonies treated with Cd or Cu contained more dead pupae within capped cells compared with control, and Se-treated colonies had lower total worker weights compared to control. Lead had a minimal effect on colony performance, although many members of the hive accumulated significant quantities of the metal. By examining the honey bee as a social organism through whole-colony assessments of toxicity, the authors found that the distribution of toxicants throughout the colony varied from metal to metal, some caste members were more susceptible to certain metals, and the colony's ability to grow over time may have been reduced in the presence of Se. Apiaries residing near metal-contaminated areas may be at risk and can suffer changes in colony dynamics and survival. © 2015 SETAC.

  17. Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity

    OpenAIRE

    Tenbusch, Matthias; Kuate, Seraphin; Tippler, Bettina; Gerlach, Nicole; Schimmer, Simone; Dittmer, Ulf; Überla, Klaus

    2008-01-01

    Abstract Background Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown promising results as a cytokine adjuvant for antiviral vaccines and in various models of tumor gene therapy. To explore whether the targeting of antigens to GM-CSF receptors on antigen-presenting cells enhances antigen-specific CD8 T-cell responses, fusion proteins of GM-CSF and ovalbumin (OVA) were expressed by DNA and adenoviral vector vaccines. In addition, bicistronic vectors allowing independent expre...

  18. Immunoregulatory effects of AFP domains on monocyte-derived dendritic cell function

    OpenAIRE

    Wibowo Gunawan A; Fanany Ismail; Anggelia Madonna R; Purwantomo Sigit; Budiyati Akterono D; Setiyono Agus; Bachtiar Indra; Utama Andi; Tai Susan

    2011-01-01

    Abstract Background Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. Results As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed ...

  19. Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study

    OpenAIRE

    Howard L. Kaufman; Amatruda, Thomas; Reid, Tony; Gonzalez, Rene; Glaspy, John; Whitman, Eric; Harrington, Kevin; Nemunaitis, John; Zloza, Andrew; Wolf, Michael; Senzer, Neil N.

    2016-01-01

    Background We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26?% in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we ...

  20. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors.

    OpenAIRE

    Dummer, R; Hoeller, C.; Gruter, I.P.; Michielin, O.

    2017-01-01

    Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tole...

  1. The reconstitution of immunocompetence by GM-CSF or IFN[gamma] after pharmacological suppression

    OpenAIRE

    Kühnle, Simone

    2000-01-01

    While immunosuppression is required to prevent graft rejection in transplantation, it increases the risk of infection. We investigated in mice immunosuppressed by different immunosuppressives (cyclosporin A, dexamethasone, tacrolimus and sirolimus), whether the innate immune system can be reactivated by granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon-gamma (IFNg). Both study drugs reconstituted the suppressed macrophage response ex vivo and in vivo, while the IL-2 and ...

  2. Picturesque Farming: The Sound of ‘Happy Britannia’ in Colonial Australia

    Directory of Open Access Journals (Sweden)

    Peter Denney

    2012-12-01

    Full Text Available This essay examines the way in which the British landscape tradition influenced perceptions of sound, noise and silence in colonial Australia, focusing on representations of rural soundscape in art and literature. It argues that poets and artists attempted to recreate an image of Australia as a new ‘Happy Britannia’, a noisy society engaged in virtuous agricultural labour. But this image was opposed to the prevailing taste for picturesque landscape, which accorded little value to human activity and placed great emphasis on silent, rural scenery. Accordingly, colonial perceptions of soundscape were ambivalent, as human-produced noise was heard as both a sign of the progress of civilisation and an obstacle to the spread of cultural refinement.

  3. Concepts for an export oriented lunar colony

    Science.gov (United States)

    Miller, Kent L.

    1990-12-01

    A model of a lunar domestic economy is presented which consists of 12 sectors, trading 21 goods and services. Material flow for operations and investments are balanced to minimize shortages and surpluses. Prices are formed by targeting a 15-35% return on assets for industry and a 15% after expenses income for labour. From this data, accounting statements, a 14 × 14 cash flow input/output matrix (consisting of 11 industrial sectors, labour, foreign trade and finance), and macroeconomic analyses are prepared which illuminate the most important links in the lunar economy. From this model conclusions are drawn regarding the matter of how best to lay the basis for sustainable colony growth and prosperity.

  4. Virtual Archaeology in an argentina colonial estancia

    Directory of Open Access Journals (Sweden)

    Florencia Vázquez

    2014-05-01

    Full Text Available This is a first approach to the application of virtual reconstruction techniques of a colonial house. In Argentina it is still uncommon to perform 3D modeling of archaeological sites and especially in historical archeology. As a first step, we used the Google SketchUp to model the country house located on the banks of the Río de la Plata (Buenos Aires. It has historical significance because it belonged to a Spanish councilman, housed hundreds of slaves and was the place where stayed the troops that carried out the Second British Invasion of Buenos Aires. In this case, the 3D modeling was useful for evaluating the future excavationa and activities of preservation of cultural heritage.

  5. Non-destructive detection for mold colonies in rice based on hyperspectra and GWO-SVR.

    Science.gov (United States)

    Sunli, Cong; Jun, Sun; Hanping, Mao; Xiaohong, Wu; Pei, Wang; Xiaodong, Zhang

    2017-08-08

    Mold contamination of grains not only contributes to inedible food, resulting in economic losses, but also leads to mold in humans and livestock, and can even be carcinogenic to them. Rice, as one of the main grain varieties, if stored improperly, is easily susceptible to mildew. In order to detect the total number of mold colonies in rice more accurately, a method based on hyperspectral imaging technology was investigated. In this paper, non-destructive detection for the total number of mold colonies in rice was performed from the angle of spectral analysis. A determination coefficient of 0.9621 for the calibration set and 0.9511 for the prediction set between the spectral data and number of mold colonies were eventually achieved by establishing the best support vector regression (SVR) model, optimized by the Gray Wolf Optimization (GWO) algorithm. Hyperspectral imaging technology combined with the optimal model (GWO-SVR) is feasible for non-destructive detection of the total number of mold colonies in rice, providing a promising tool for the mold detection of other agricultural products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Switching of colony morphology and adhesion activity of Trichosporon asahii clinical isolates.

    Science.gov (United States)

    Ichikawa, Tomoe; Yoshiyama, Nao; Ohgane, Yuzuha; Ikeda, Reiko

    2016-02-01

    Trichosporon asahii is a pathogenic yeast that causes trichosporonosis, a deep-seated infection, in immunocompromised hosts. Pathogenic factors involved in this infection have not been investigated in detail, but morphological phenotype switching is thought to be important for T. asahii pathogenesis. Therefore, we analyzed adhesion, which may be a key early step in T. asahii infection, after morphological phenotype switching. T. asahii clinical isolates show several colony morphologies. In this study, colonies showing white-farinose (W), off-white-smooth (O), off-white-rugose (OR), smooth (S), and yellowish-white (Y) morphologies were obtained from three isolates and compared in an adhesion assay performed in cell culture dishes. At least one type of colony morphology from each clinical isolate adhered strongly to the culture dish surface, although the colony type that displayed strong adherence varied among the strains. Thus, morphological phenotype switching altered the adhesion of T. asahii strains. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Dynamics of the Presence of Israeli Acute Paralysis Virus in Honey Bee Colonies with Colony Collapse Disorder

    Directory of Open Access Journals (Sweden)

    Chunsheng Hou

    2014-05-01

    Full Text Available The determinants of Colony Collapse Disorder (CCD, a particular case of collapse of honey bee colonies, are still unresolved. Viruses including the Israeli acute paralysis virus (IAPV were associated with CCD. We found an apiary with colonies showing typical CCD characteristics that bore high loads of IAPV, recovered some colonies from collapse and tested the hypothesis if IAPV was actively replicating in them and infectious to healthy bees. We found that IAPV was the dominant pathogen and it replicated actively in the colonies: viral titers decreased from April to September and increased from September to December. IAPV extracted from infected bees was highly infectious to healthy pupae: they showed several-fold amplification of the viral genome and synthesis of the virion protein VP3. The health of recovered colonies was seriously compromised. Interestingly, a rise of IAPV genomic copies in two colonies coincided with their subsequent collapse. Our results do not imply IAPV as the cause of CCD but indicate that once acquired and induced to replication it acts as an infectious factor that affects the health of the colonies and may determine their survival. This is the first follow up outside the US of CCD-colonies bearing IAPV under natural conditions.

  8. Dynamics of the Presence of Israeli Acute Paralysis Virus in Honey Bee Colonies with Colony Collapse Disorder

    Science.gov (United States)

    Hou, Chunsheng; Rivkin, Hadassah; Slabezki, Yossi; Chejanovsky, Nor

    2014-01-01

    The determinants of Colony Collapse Disorder (CCD), a particular case of collapse of honey bee colonies, are still unresolved. Viruses including the Israeli acute paralysis virus (IAPV) were associated with CCD. We found an apiary with colonies showing typical CCD characteristics that bore high loads of IAPV, recovered some colonies from collapse and tested the hypothesis if IAPV was actively replicating in them and infectious to healthy bees. We found that IAPV was the dominant pathogen and it replicated actively in the colonies: viral titers decreased from April to September and increased from September to December. IAPV extracted from infected bees was highly infectious to healthy pupae: they showed several-fold amplification of the viral genome and synthesis of the virion protein VP3. The health of recovered colonies was seriously compromised. Interestingly, a rise of IAPV genomic copies in two colonies coincided with their subsequent collapse. Our results do not imply IAPV as the cause of CCD but indicate that once acquired and induced to replication it acts as an infectious factor that affects the health of the colonies and may determine their survival. This is the first follow up outside the US of CCD-colonies bearing IAPV under natural conditions. PMID:24800677

  9. Ant Colonies Do Not Trade-Off Reproduction against Maintenance.

    Directory of Open Access Journals (Sweden)

    Boris H Kramer

    Full Text Available The question on how individuals allocate resources into maintenance and reproduction is one of the central questions in life history theory. Yet, resource allocation into maintenance on the organismic level can only be measured indirectly. This is different in a social insect colony, a "superorganism" where workers represent the soma and the queen the germ line of the colony. Here, we investigate whether trade-offs exist between maintenance and reproduction on two levels of biological organization, queens and colonies, by following single-queen colonies of the ant Cardiocondyla obscurior throughout the entire lifespan of the queen. Our results show that maintenance and reproduction are positively correlated on the colony level, and we confirm results of an earlier study that found no trade-off on the individual (queen level. We attribute this unexpected outcome to the existence of a positive feedback loop where investment into maintenance (workers increases the rate of resource acquisition under laboratory conditions. Even though food was provided ad libitum, variation in productivity among the colonies suggests that resources can only be utilized and invested into additional maintenance and reproduction by the colony if enough workers are available. The resulting relationship between per-capita and colony productivity in our study fits well with other studies conducted in the field, where decreasing per-capita productivity and the leveling off of colony productivity have been linked to density dependent effects due to competition among colonies. This suggests that the absence of trade-offs in our laboratory study might also be prevalent under natural conditions, leading to a positive association of maintenance, (= growth and reproduction. In this respect, insect colonies resemble indeterminate growing organisms.

  10. Long-lasting partial remission by Interferon-alpha treatment in a child with essential thrombocythemia.

    Science.gov (United States)

    Szegedi, István; Benko, Ilona; Mero, Gabriella; Prinzinger, Agota; Kappelmayer, János; Kiss, Csongor

    2007-10-15

    Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic lineage, and association with thrombotic or bleeding episodes. It is extremely rare in childhood and frequently presents without evident clinical signs. We describe a 3-year-old girl with severe headache and dizziness suffering from ET, who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of this patient did not exhibit spontaneous colony formation but responded to recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a sustained partial remission with platelet counts varying between 400 and 600 x 10(3)/microl. (c) 2007 Wiley-Liss, Inc.

  11. Breeding history of the Stanford colony of narcoleptic dogs.

    Science.gov (United States)

    Cederberg, R; Nishino, S; Dement, W C; Mignot, E

    1998-01-10

    Narcolepsy is a disabling sleep disorder of unknown aetiology. In humans, the disease is mostly sporadic, with a few familial cases having been reported. In 1973 a sporadic case of narcolepsy was reported in a poodle, and in 1975 familial cases of narcolepsy occurred in dobermanns. As with human narcoleptics, these narcoleptic dogs exhibited excessive daytime sleepiness and cataplexy. A colony of narcoleptic dogs was established at Stanford University in 1976 to study the pathophysiology of the disease. Between 1976 and 1995, a total of 669 animals of various breeds were born, of which 487 survived. Dobermanns accounted for 78 per cent of the total. The narcolepsy genotype in dobermanns had no significant influence on puppy mortality rate (numbers of stillborn and survival rate). The sex, maternal parity or the age of the sire or dam had no significant effect. The percentage of stillborn puppies increased from 6.1 per cent in outbred litters to 15.4 per cent in inbred litters (P = 0.10). Birth season also had a significant effect, and the highest survival rate (P = 0.02), and the lowest percentage of stillborn puppies (P = 0.09) occurred between April and June.

  12. 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

    Science.gov (United States)

    Daluge, S M; Good, S S; Faletto, M B; Miller, W H; St Clair, M H; Boone, L R; Tisdale, M; Parry, N R; Reardon, J E; Dornsife, R E; Averett, D R; Krenitsky, T A

    1997-05-01

    1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human

  13. Between Past and Present: The Sociopsychological Constructs of Colonialism, Coloniality and Postcolonialism.

    Science.gov (United States)

    Tomicic, Ana; Berardi, Filomena

    2018-03-01

    If one of the major aspirations of postcolonial theory is to re-establish a balance in the relationship between the (former) colonizer and the colonized by engaging the voices of the "subaltern", and on the other hand to illuminate how power relations of the present are embedded in history (Mills 2007), we argue that important theoretical insights might inform research by anchoring post-colonial theory within a sociopsychological framework. While there is a growing corpus of sociopsychological research articles focusing on how major geopolitical events and historical processes bear on people's lives, we aim to investigate the theoretical potential of postcolonial theory within the disciplines aiming at a sociopsychological approach. By focusing on the social dynamics of power imbalances, post-colonial theory finds its operational meaning: the feelings stemming from actions committed in the past are indeed crucial in determining reparatory attitudes and policies towards members of former colonized groups. Firstly, drawing from the sociopsychological scientific production related to consequences of colonial past, seen in recent years as a growing research interest in the field, we will explore patterns and trends through a thematic analysis of literature. Social Psychology as well as adjacent disciplines can greatly benefit from this theoretical fertilization, especially in the way post-colonial ideologies relate to the symbolic promotion versus exclusion of indigenous culture (Sengupta et al., International Journal of Intercultural Relations, 36(4), 506-517, 2012). Furthermore, by comparing and contrasting the ideological cosmologies relating to this particular topic, this study aims to establish the state of knowledge in the field, to identify how research methods and thematic fields are paired, to find "gaps" and create spaces for research that become integrative of postcolonial theory. While focusing on academic production, we also hope to contribute to develop

  14. Internal cave gating for protection of colonies of the endangered gray bat (Myotis grisescens)

    Science.gov (United States)

    Martin, K.W.; Leslie, David M.; Payton, M.E.; Puckette, William L.; Hensley, S.L.

    2003-01-01

    Persistent human disturbance is a major cause for the decline in populations of many cave-dwelling bats and other sensitive cave-obligate organisms. Cave gating has been used to climinate human disturbance, but few studies have assessed directly the impact of such management activities on resident bats. In northeastern Oklahoma, USA, 25 entrances of caves inhabited by two endangered species and one endangered subspecies of bats are protected from human entry with internal gates. Because cave gates may impede ingress and egress of bats at caves, we evaluated the impacts of internal gates before and after their construction at six colonies of endangered gray bats (Myotis grisescens) from 1981 to 2001. No caves were abandoned by gray bats after the construction of internal gates; in fact, total numbers of gray bats using the six caves increased from 60,130 in 1981 to 70,640 in 2001. Two caves harbored more gray bats after gating, and three caves had no change in gray bat numbers after gating. We also compared initiations of emergences at three gated and three open-passage caves in June and July 1999-2000. No differences in timing of initiation of emergence were found between colonies in gated versus open-passage caves. Our results support the use of internal gates to protect and thereby enhance recovery of colonies of endangered gray bats. Additional research is encouraged to confirm that our observations on gray bats are generally applicable to other species of cave-dwelling bats.

  15. Generation of mutation hotspots in ageing bacterial colonies

    DEFF Research Database (Denmark)

    Sekowska, Agnieszka; Wendel, Sofie; Nørholm, Morten

    How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation:...

  16. Discover for Yourself: An Optimal Control Model in Insect Colonies

    Science.gov (United States)

    Winkel, Brian

    2013-01-01

    We describe the enlightening path of self-discovery afforded to the teacher of undergraduate mathematics. This is demonstrated as we find and develop background material on an application of optimal control theory to model the evolutionary strategy of an insect colony to produce the maximum number of queen or reproducer insects in the colony at…

  17. Estimating 3-dimensional colony surface area of field corals

    Science.gov (United States)

    Colony surface area is a critical descriptor for biological and physical attributes of reef-building (scleractinian, stony) corals. The three-dimensional (3D) size and structure of corals are directly related to many ecosystem values and functions. Most methods to estimate colony...

  18. Idiocy and the Law in Colonial New England.

    Science.gov (United States)

    Wickham, Parnel

    2001-01-01

    A review of laws and records of the courts of colonial New England indicates early laws of Massachusetts extended certain rights to idiots: they authorized the transfer of property, exonerated idiots who committed capital crimes, and extended relief to impoverished idiots. The relationship between colonial laws and present legislation is examined.…

  19. How did Europe Rule Africa? Dialectics of Colonialism and African ...

    African Journals Online (AJOL)

    The question of how Europe ruled Africa relates to the crucial issues of settlernative identity as constructions of colonialism as well as political consciousness formation and development among the colonized as well as the colonizers. Because colonialism operated ambiguously throughout its life to the extent of hiding its ...

  20. Colonial Military Intelligence in the Zulu Rebellion, 1906 | Thompson ...

    African Journals Online (AJOL)

    In the Zulu Rebellion of 1906, the Natal Militia defeated the Zulu rebels without British imperial forces having to intervene in the conflict. The colonial forces were well adapted to the local circumstances, but in one important respect they drew heavily on imperial experience, namely military field intelligence. Colonial military ...

  1. Embodying colonial photography: remembering violence in Tabee Toean

    NARCIS (Netherlands)

    Bijl, P.

    2011-01-01

    This article is about bodily interactions with photographs. Taking an interview with a veteran from the Dutch colonial army filmed for the documentary Tabee Toean (1995) as its case study, it focuses on the ways in which this man frames these images of colonial warfare through three types of bodily

  2. The Efficiency of the Assay for Haemopietic Colony Forming Cells

    NARCIS (Netherlands)

    Lahiri, S.K.; Keizer, H.J.; Putten, L.M.v. (L. M. van)

    1970-01-01

    textabstractThe quantitative efficiency of the spleen colony assay in mice is discussed in the light of recent findings on the kinetics of colony forming cells. Arguments are presented showing that the f factor, the 2 hr CFU recovery fraction in the spleen, markedly over‐estimates the assay

  3. Breeding site selection by colonial waterbirds given various ...

    African Journals Online (AJOL)

    The number of active colonial waterbird nests at a series of four small constructed wetlands in Cape Town was counted monthly from 1999 to 2008. In total 491 pairs belonging to 11 waterbird species were involved. Between 1997 and 2004 a number of different artificial structures were used to attract colonial waterbirds to ...

  4. Regionally coherent trends in colonies of African penguins ...

    African Journals Online (AJOL)

    From 1987 to 2005, numbers of African penguins Spheniscus demersus breeding in South Africa's Western Cape Province increased by about 50%. Numbers decreased at the four northernmost colonies in the region: Lambert's Bay and the three colonies in Saldanha Bay, although at Jutten Island the decrease is inferred ...

  5. Factors influencing growth of the African penguin colony at Boulders ...

    African Journals Online (AJOL)

    This paper reports on growth of the Boulders colony of African penguins Spheniscus demersus from inception in 1985 to the present. More than 900 pairs now breed there. Growth of the colony slowed in 1995 and 1996 and reversed in 1998, coinciding with periods of low abundance of Cape anchovy Engraulis capensis off ...

  6. Toxoplasmosis in a colony of New World monkeys

    DEFF Research Database (Denmark)

    Dietz, H.H.; Henriksen, P.; Bille-Hansen, Vivi

    1997-01-01

    In a colony of New World monkeys five tamarins (Saguinus oedipus, Saguinus labiatus and Leontopithecus rosal. rosal.), three marmosets (Callithrix jacchus and Callithrix pygmaea) and one saki (Pithecia pithecia) died suddenly. The colony comprised 16 marmosets, 10 tamarins and three sakis. The ma...

  7. Readers and Writers in Colonial Natal (1843–1910) | Christison ...

    African Journals Online (AJOL)

    The purpose of this essay is to present a broad outline of ways in which literary or imaginative texts were circulated and consumed in Natal Colony in the years 1843–1910. It shows how, at least initially, the majority of these texts originated abroad, but how increasingly colonials began to supply their own literary ...

  8. The colonial 'civilizing process' in Dutch Formosa 1624-1662

    NARCIS (Netherlands)

    Chiu, Hsin-hui

    2007-01-01

    This is a study of the colonial ‘civilizing process’ in Dutch Formosa (Present-day Taiwan) between 1624 and 1662. Drawing inspiration from Norbert Elias, this study stresses on ‘the colonial “civilizing process” ’ which is applied to the inexorable process of retreat from the era of ‘Aboriginal

  9. Post-Colonial Practice in Chimamanda Ngozi Adichie's Purple ...

    African Journals Online (AJOL)

    The fact that colonialism has come and gone in Africa, does not mean that it has taken along with it all the draconian effects it has on the continent of Africa. Therefore, African writers in order for them to get out of a gridlock situation that colonialism has placed on the continent of Africa, have decided to look for means and ...

  10. Resisting the Coloniality of English: A Research Review of Strategies

    Science.gov (United States)

    Hsu, Funie

    2017-01-01

    The colonial legacy of English instruction has become especially relevant within the field of TESOL. While it is promising that increasing attention is being paid to the issue of colonialism and its historical and contemporary impact on the teaching of English, educators might be left without a clear sense of how to traverse the precarious path of…

  11. Honeybee colony marketing and its implications for queen rearing ...

    African Journals Online (AJOL)

    Government and NGOs are promoting beekeeping as a tool for poverty alleviation in Ethiopia. This increased promotion is creating increasing demand for bee colonies in the Northern part of the country such as Tigray region. Thus, colony marketing is an important venture in Werieleke district of Tigray region. This research ...

  12. 'Administering the Medicine': Progressive Education, Colonialism, and the State.

    Science.gov (United States)

    Cote, Joost

    2001-01-01

    Draws comparisons between the Australian education directors, Frank Tate and Jacques Henry Abendanon. Discusses educational reform issues based on racial contexts and social, political, and cultural aspects in the British colony of Victoria and the Dutch colony of Java. Concludes that, though their politcal contexts are different, their views are…

  13. Cormorants as visitors in the Vorsø colony

    DEFF Research Database (Denmark)

    Bregnballe, Thomas; Vinas, Marta Mas; Gregersen, Jens

    2011-01-01

    Like other seabirds Great Cormorants Phalacrocorax carbo sinensis are known to prospect in potential breeding colonies during their first years of life before they settle to breed. Based on daily resightings of colour-ringed cormorants in the old Vorsø colony we examined the difference between na...

  14. Colonial Modernity and the African Worldview: Theorising and ...

    African Journals Online (AJOL)

    The Gramscian concept of hegemony and Jean and John Comaroff's concept of cultural and colonial encounters are used to assist in teasing out deeper meaning in the encounter between the Ndebele and the early Christian missionaries prior to inscription of settler colonialism in the area lying between the Limpopo and ...

  15. Counter-Insurgency in the Cape Colony, 1872 - 1882 | Kotze ...

    African Journals Online (AJOL)

    The colonial government expected unrealistic strategic results from the colonial armed forces. Military reforms were mostly reactive and too little was done too late. The Molteno as well as the Sprigg ministry eventually paid the highest political price for the failure of their respective defence schemes not least of which was the ...

  16. Automatic counting and classification of bacterial colonies using hyperspectral imaging

    Science.gov (United States)

    Detection and counting of bacterial colonies on agar plates is a routine microbiology practice to get a rough estimate of the number of viable cells in a sample. There have been a variety of different automatic colony counting systems and software algorithms mainly based on color or gray-scale pictu...

  17. Colonial conquest in central Madagascar : who resisted what?

    NARCIS (Netherlands)

    Ellis, S.; Abbink, G.J.; Bruijn, M.E. de.; Walraven, van K.

    2003-01-01

    A rising against French colonial rule in central Madagascar (1895-1898) appeared in the 1970s as a good example of resistance to colonialism, sparked by France's occupation of Madagascar. Like many similar episodes in other parts of Africa, it was a history that appeared, in the light of later

  18. Decolonial, post-colonial, post-apartheid - reflections on some ...

    African Journals Online (AJOL)

    The waves of student protest in South Africa in 2015 – 2016 reflect the failure of an ANC government to deconstruct the country's deeply embedded colonial legacy, both in ideas and in its myriad practical manifestations. The writer uncovers the effects of layers of colonial hegemony from its early onset to the present and ...

  19. Memory contested, locality transformed : representing Japanese colonial 'heritage' in Taiwan

    NARCIS (Netherlands)

    Chiang, Min-Chin

    2012-01-01

    In the search for a Taiwanese identity rooted in the land of Taiwan the Japanese colonial past plays an ambiguous role. The Japanese colonial sites became a constituent part of the new identity and cultural narrative of Taiwan in the 1990s and 2000s, when a memory boom was experienced in Taiwan

  20. The Sociocultural Significance of Court Institutions in Colonial Virginia

    Directory of Open Access Journals (Sweden)

    Pavel V. Vostrikov

    2017-09-01

    Full Text Available In this article the author examines the sociocultural significance of courts in colonial Virginia. Virginia was agrarian “tobacco” colony, where the settlements of urban type did not get proper development. In this connection, court days were very important occasions for social gatherings, when colonists not only might participate in court hearings, but became involved in various social interactions such as news exchange, business transactions, cockfighting, horse racing and attending taverns. If not found in rare towns court buildings weresituated at road junctions and other convenient places to be more easily accessible for inhabitants of the colony. The author also provides a glimpse into the issues of law and order, crime and punishment as well as the general state of the colonial system of justice. During the colonial period the differences between judicial, executive and legislative branches of government were not distinct yet and the institution of the county court had immense importance as it combined all the three types of power on a local level. The court of oyer and terminer dealt with criminal offences. The General court in Williamsburg, the colonial capital, was the main court in Virginia which considered the most crucial cases. The colonial legal system was initially based on English traditions and precedents but it was constantly modified largely due to the singularities of the colony such as abundance of free land and chattel slavery.

  1. Nigeria's Fiscal Deficits: A History of its Colonial Foundations, 1899 ...

    African Journals Online (AJOL)

    This paper shows that deficit financing of public expenditure by the Nigerian government is however not a recent issue and that it can be traced to the formative years of Nigeria's public finance in the colonial period. The paper however argues that unlike the current practice, deficit financing was driven more in the colonial ...

  2. Colony differences in termiticide transfer studies, a role for behavior?

    Science.gov (United States)

    Thomas Shelton

    2010-01-01

    Donor-recipient termiticide transfer laboratory tests were performed by using destructive sampling with two delayed-action non-repellent (DANR) termiticides against each of three colonies of Reticulitermes flavipes (Kollar). Two of the three colonies showed no response to indoxacarb, but all three showed a response to chlorantraniliprole. These results indicate that...

  3. The Colonial Situation: Complicities and Distinctions from the Surrealist Image

    Directory of Open Access Journals (Sweden)

    Pedro Pablo Gómez

    2011-05-01

    Full Text Available In this work, taking as baseline the thought of Aimé Césaire and Franz Fanon —keeping in mind the closeness of the Negritude movement with surrealism—, we propose to approach the modernity/coloniality problem, appealing to the denominated surrealist image of beauty. In the first part the colonial situation is approached, in the second the colonial situation from the logic of surrealist image, and in the third the possibility of a decolonial universal or pluriversal is raised. In general terms, exploring the existent link between the “surrealist image” and the colonial structure of modernity —that generates the denominated colonial situation—, we aspire to approach what could be a decolonial aesthetic that, as general problem, will be tackled in later works.

  4. Iridovirus and microsporidian linked to honey bee colony decline.

    Directory of Open Access Journals (Sweden)

    Jerry J Bromenshenk

    Full Text Available BACKGROUND: In 2010 Colony Collapse Disorder (CCD, again devastated honey bee colonies in the USA, indicating that the problem is neither diminishing nor has it been resolved. Many CCD investigations, using sensitive genome-based methods, have found small RNA bee viruses and the microsporidia, Nosema apis and N. ceranae in healthy and collapsing colonies alike with no single pathogen firmly linked to honey bee losses. METHODOLOGY/PRINCIPAL FINDINGS: We used Mass spectrometry-based proteomics (MSP to identify and quantify thousands of proteins from healthy and collapsing bee colonies. MSP revealed two unreported RNA viruses in North American honey bees, Varroa destructor-1 virus and Kakugo virus, and identified an invertebrate iridescent virus (IIV (Iridoviridae associated with CCD colonies. Prevalence of IIV significantly discriminated among strong, failing, and collapsed colonies. In addition, bees in failing colonies contained not only IIV, but also Nosema. Co-occurrence of these microbes consistently marked CCD in (1 bees from commercial apiaries sampled across the U.S. in 2006-2007, (2 bees sequentially sampled as the disorder progressed in an observation hive colony in 2008, and (3 bees from a recurrence of CCD in Florida in 2009. The pathogen pairing was not observed in samples from colonies with no history of CCD, namely bees from Australia and a large, non-migratory beekeeping business in Montana. Laboratory cage trials with a strain of IIV type 6 and Nosema ceranae confirmed that co-infection with these two pathogens was more lethal to bees than either pathogen alone. CONCLUSIONS/SIGNIFICANCE: These findings implicate co-infection by IIV and Nosema with honey bee colony decline, giving credence to older research pointing to IIV, interacting with Nosema and mites, as probable cause of bee losses in the USA, Europe, and Asia. We next need to characterize the IIV and Nosema that we detected and develop management practices to reduce honey

  5. Iridovirus and Microsporidian Linked to Honey Bee Colony Decline

    Science.gov (United States)

    Bromenshenk, Jerry J.; Henderson, Colin B.; Wick, Charles H.; Stanford, Michael F.; Zulich, Alan W.; Jabbour, Rabih E.; Deshpande, Samir V.; McCubbin, Patrick E.; Seccomb, Robert A.; Welch, Phillip M.; Williams, Trevor; Firth, David R.; Skowronski, Evan; Lehmann, Margaret M.; Bilimoria, Shan L.; Gress, Joanna; Wanner, Kevin W.; Cramer, Robert A.

    2010-01-01

    Background In 2010 Colony Collapse Disorder (CCD), again devastated honey bee colonies in the USA, indicating that the problem is neither diminishing nor has it been resolved. Many CCD investigations, using sensitive genome-based methods, have found small RNA bee viruses and the microsporidia, Nosema apis and N. ceranae in healthy and collapsing colonies alike with no single pathogen firmly linked to honey bee losses. Methodology/Principal Findings We used Mass spectrometry-based proteomics (MSP) to identify and quantify thousands of proteins from healthy and collapsing bee colonies. MSP revealed two unreported RNA viruses in North American honey bees, Varroa destructor-1 virus and Kakugo virus, and identified an invertebrate iridescent virus (IIV) (Iridoviridae) associated with CCD colonies. Prevalence of IIV significantly discriminated among strong, failing, and collapsed colonies. In addition, bees in failing colonies contained not only IIV, but also Nosema. Co-occurrence of these microbes consistently marked CCD in (1) bees from commercial apiaries sampled across the U.S. in 2006–2007, (2) bees sequentially sampled as the disorder progressed in an observation hive colony in 2008, and (3) bees from a recurrence of CCD in Florida in 2009. The pathogen pairing was not observed in samples from colonies with no history of CCD, namely bees from Australia and a large, non-migratory beekeeping business in Montana. Laboratory cage trials with a strain of IIV type 6 and Nosema ceranae confirmed that co-infection with these two pathogens was more lethal to bees than either pathogen alone. Conclusions/Significance These findings implicate co-infection by IIV and Nosema with honey bee colony decline, giving credence to older research pointing to IIV, interacting with Nosema and mites, as probable cause of bee losses in the USA, Europe, and Asia. We next need to characterize the IIV and Nosema that we detected and develop management practices to reduce honey bee losses

  6. Colonial nesting Yellow-crowned Night Herons on the San Antonio River Walk

    Science.gov (United States)

    Boal, Clint W.

    2010-01-01

    Yellow-crowned Night Herons (Nyctinassa violacea) typically nest as single pairs or in small colonies of about four pairs with high internest distances. They are also reported as susceptible to disturbance and to avoid habitat with high human use. However, some Yellowcrowned Night Herons habituate to human-dominated landscapes and nest in residential areas. I located a colony of nesting Yellow-crowned Night Herons in San Antonio, Texas on the River Walk, a popular tourist destination with an estimated 2.5 million visitors annually. I located 68 and 71 active nests in 2008 and 2009, respectively. This suggests the breeding population of the colony was 142 adult birds (77 adult herons/linear km of River Walk) in 2009. Herons occurred in a colony with three nesting aggregations situated 241 (±14 SD) m apart. Aggregations averaged 23.7 (±8.7 SD) nests each with one–nine nests per tree; nest trees within each aggregation were usually adjacent. Nests averaged 16.7 m (±4.1 SD) above ground, with 56% of nests over the river, 23% over sidewalks, 17% over dining areas, and 3% over landscaping. Only bald cypress (Taxodium distichum) was used for nest trees, and these were significantly taller and larger in diameter than random bald cypress trees. The herons were habituated to pedestrian activities, often perching only a few meters over sidewalks or dining areas, and foraging along the water’s edge as pedestrians passed within 4–5 m. Nests located over dining areas and sidewalks do impose some management issues. It is apparent the species is capable of habituating to human activities to exploit suitable urban settings for nesting and foraging habitat.

  7. [Japan's Oriental medicine policy in colonial Korea].

    Science.gov (United States)

    Park, Yunjae

    2008-06-01

    During its colonization of Korea, the Japanese Empire used the Western medicine as a tool for advertising its advanced culture. However, the medical workforce available in Korea was insufficient. The Rule for Uisaeng (Oriental medicine practitioner) was an ordinance decreed in 1913 with a purpose of supplementing the medical workforce. As the Oriental medicine practitioners became official medical workforce, the Japanese Empire could mobilize them in a hygienic administration such as prevention of epidemics. The Uisaengs also tried to adapt themselves to the colonial environment by studying Western medicines. However, the distrust of the Japanese Empire in Oriental medicine continued until 1920s. Manchurian Incident in 1931 brought a change. As the relationship with China aggravated, the provision of medical herb became unstable and the Japanese Empire began to encourage using Oriental medical herb following the Movement for Improving Rural Region Economy. An attempt of the Japanese Empire to utilize the medical herb resulted in a plan to make the Oriental medical herb officinal. The goal was to organize and standardize the Oriental medical herb through a research by the Medical Herb Investigation Committee. However, the medical herb on the table was the one verified by the Western medicine. That is, it was not a traditional medical herb that uses the original theory of Oriental medicine. There was a minority opinion arguing that they should study the Oriental medicine itself. However, that argument was also based on the theory and principles of the Western medicine. Even though an attempt to make full use of Uisaengs expanded as the war continued, the major medical workforce that the Japanese Empire relied on was those trained in Western medicine. In other words, the Japanese Empire did not give a full credit to the Oriental medicine during the colonial era. During the colonization, Japanese Empire used Oriental medicine under the nominal reason of lack of medical

  8. Tapping Environmental History to Recreate America's Colonial Hydrology

    Science.gov (United States)

    Pastore, C. L.; Green, M.; Duncan, J.; Bain, D.; Pellerin, B.; Kim, H.

    2008-12-01

    Throughout American history water has played a central role in biological and economic exchange. Water and the energy derived from it have largely determined patterns of human settlement. Humans, likewise, altered local and regional hydrosystems to meet their needs. Drawing from work generated at the Hydrologic Synthesis Institute held at the Massachusetts Institute of Technology during summer 2008, this study demonstrates that environmental history can generate new and important questions for hydrologists and that the science of hydrology can shed new light on early American history. The summer synthesis institute charted regional hydrologic change from Chesapeake Bay to the St. John River, between 1600 and 1800. Historical analyses that examine the period of first European settlement provide hydrologists with a more accurate understanding of baseline environments and how they responded to the principal drivers of hydrologic change, including human governance, water-engineering, land-cover modification, and climate change. Proxy data, such as colonial census records, import/export statistics, tax information, and weather observations, among others, can produce quantifiable assessments of hydrologic change in the distant past. Examining how regional hydrosystems functioned in the past and how humans changed them over time promises to shed new light on how present and future hydrosystems will respond to human-induced environmental change. The human-water linkage also has profound implications for history. Hydrologic modeling shows promise as a new form of historical evidence. Quantitative analyses of hydrosystems can take historical analyses beyond scattered 'perceptions' conveyed through more traditional anecdotal sources. Hydrologic evidence could provide new insights into patterns of population distribution and land management. Charting the metrics of hydrologic change, such as water availability, residency time, or the timing of peak and low flows, may shed new

  9. Collective Memories of Portuguese Colonial Action in Africa: Representations of the Colonial Past among Mozambicans and Portuguese Youths

    Directory of Open Access Journals (Sweden)

    João Feijó

    2010-05-01

    Full Text Available Social representations of the colonization and decolonization processes among young people from a former European colonial power (Portugal and from an African ex-colony (Mozambique were investigated through surveys using open- and closed-ended questions about national history, focusing on the identity functions of collective memories. Hegemonic and contested representations were found of the most prominent events related to Portuguese colonization of Mozambique, arousing a range of collective emotions. A central place is occupied by memories of the Colonial War, which ended with the Carnation Revolution in Portugal and the subsequent independence of the Portuguese African colonies. Overall, the depiction of colonialism was more negative for Mozambican than for Portuguese participants. The violent effects of colonial action were very salient in Mozambican memories, which stressed the most oppressive aspects of the colonial period, associated with slave trade and brutal repression. On the Portuguese side, the idealization of the voyages of discovery persisted, obscuring the most violent effects of colonial expansion. However, collective memories of colonization of former colonizer and former colonized do not simply stand opposed. Both Mozambican and Portuguese participants reported ambivalent feelings towards the colonization process.

  10. For the youth : juvenile delinquency, colonial civil society and the late colonial state in the Netherlands Indies, 1872-1942

    NARCIS (Netherlands)

    Dirks, Annelieke

    2011-01-01

    This dissertation project focuses on forced re-education policies for juvenile delinquents in the Netherlands Indies (now Indonesia) and uses this topic to show the interaction between a 'modernizing' Dutch colonial state and the growth of a colonial civil society, between approximately 1872 and

  11. Urban life of Galapagos sea lions (Zalophus wollebaeki) on San Cristobal Island, Ecuador: colony trends and threats

    Science.gov (United States)

    Denkinger, Judith; Gordillo, Luis; Montero-Serra, Ignasi; Murillo, Juan Carlos; Guevara, Nataly; Hirschfeld, Maximilian; Fietz, Katharina; Rubianes, Francisco; Dan, Michael

    2015-11-01

    Worldwide, pristine environments are influenced by human societies. In the Galapagos Islands, the endangered, endemic Galapagos sea lion (Zalophus wollebaeki) has formed one of the biggest colonies within the town center of Puerto Baquerizo Moreno. About 8,000 people live there and human wildlife interactions occur daily. With colony counts and direct observations from 2008 to 2012, we analyze cause of death, injuries and disease of urban sea lion colonies at Wreck Bay. Population increase since 2008 can be attributed to an immigration of adult sea lions in 2010, resulting in an increase in the pup and juvenile production in 2011 and 2012. Pup mortality increased drastically to 2009 and again in 2011 and 2012. Besides pup mortality, most of the deaths are caused by increased disease incidences and human activity. Our observations suggest that overall 65% of the injuries observed are produced by human interaction. The increase in threats leading to death, injuries or disease can have long-term effects on the population. Although threats that cause physical injuries can be managed locally, sea lions range movements contributes to the spread of infectious pathogens, which may affect neighbor colonies and potentially have an impact on the survival of the species. Our study reveals the need of stronger efforts towards a more complete understanding of threats and especially disease spread among Galapagos Sea lions in urban environments and the establishment of more effective management measures.

  12. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Aladdin, H

    2000-01-01

    This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was ...

  13. Interactions of erythropoietin, granulocyte colony-stimulating factor, stem cell factor, and interleukin-11 on murine hematopoiesis during simultaneous administration

    NARCIS (Netherlands)

    Roeder, [No Value; de Haan, G; Engel, C; Nijhof, W; Dontje, B; Loeffler, M

    1998-01-01

    We investigated how in vivo effects of single hematopoietic cytokines change if given in combination for a prolonged time. Mice were treated with every combination of recombinant human (rh) erythropoietin (EPO), rh granulocyte colony-stimulating factor (G-CSF), recombinant rat (rr) stem cell factor

  14. Artificial bee colony in neuro - Symbolic integration

    Science.gov (United States)

    Kasihmuddin, Mohd Shareduwan Mohd; Sathasivam, Saratha; Mansor, Mohd. Asyraf

    2017-08-01

    Swarm intelligence is a research area that models the population of the swarm based on natural computation. Artificial bee colony (ABC) algorithm is a swarm based metaheuristic algorithm introduced by Karaboga to optimize numerical problem. Pattern-SAT is a pattern reconstruction paradigm that utilized 2SAT logical rule in representing the behavior of the desired pattern. The information of the desired pattern in terms of 2SAT logic is embedded to Hopfield neural network (HNN-P2SAT) and the desired pattern is reconstructed during the retrieval phase. Since the performance of HNN-P2SAT in Pattern-SAT deteriorates when the number of 2SAT clause increased, newly improved ABC is used to reduce the computation burden during the learning phase of HNN-P2SAT (HNN-P2SATABC). The aim of this study is to investigate the performance of Pattern-SAT produced by ABC incorporated with HNN-P2SAT and compare it with conventional standalone HNN. The comparison is examined by using Microsoft Visual Basic C++ 2013 software. The detailed comparison in doing Pattern-SAT is discussed based on global Pattern-SAT, ratio of activated clauses and computation time. The result obtained from computer simulation indicates the beneficial features of HNN-P2SATABC in doing Pattern-SAT. This finding is expected to result in a significant implication on the choice of searching method used to do Pattern-SAT.

  15. Ant Colony Optimisation for Backward Production Scheduling

    Directory of Open Access Journals (Sweden)

    Leandro Pereira dos Santos

    2012-01-01

    Full Text Available The main objective of a production scheduling system is to assign tasks (orders or jobs to resources and sequence them as efficiently and economically (optimised as possible. Achieving this goal is a difficult task in complex environment where capacity is usually limited. In these scenarios, finding an optimal solution—if possible—demands a large amount of computer time. For this reason, in many cases, a good solution that is quickly found is preferred. In such situations, the use of metaheuristics is an appropriate strategy. In these last two decades, some out-of-the-shelf systems have been developed using such techniques. This paper presents and analyses the development of a shop-floor scheduling system that uses ant colony optimisation (ACO in a backward scheduling problem in a manufacturing scenario with single-stage processing, parallel resources, and flexible routings. This scenario was found in a large food industry where the corresponding author worked as consultant for more than a year. This work demonstrates the applicability of this artificial intelligence technique. In fact, ACO proved to be as efficient as branch-and-bound, however, executing much faster.

  16. Was Fundamental Education Another Form Of Colonialism?

    Science.gov (United States)

    Watras, Joseph

    2007-01-01

    A description of the work of Pedro Tamesis Orata provides an opportunity to investigate the conflicts that can occur when educators seek to reduce poverty while trying to respect indigenous cultures. A native of the Philippines, Orata completed his doctoral studies at the Ohio State University in 1927. During US President Franklin Roosevelt's New Deal, he accepted the position of school principal for the US Bureau of Indian Affairs. After World War II, he directed the spread of fundamental education through the United Nations Educational, Scientific and Cultural Organization (UNESCO). In his final years, he returned to the Philippines where he began a movement to spread what were called self-help high schools. In these activities, Orata taught people to follow John Dewey's five steps of thinking while working to improve their standards of living. In the 1970s, educators, such as Paulo Freire, complained that problem-solving methods, similar to those Orata favored, reinforced the oppressive aspects of formerly colonial societies. While Freire may have been overly critical, conflicts among cultural orientations appear to be unavoidable. The hope behind this investigation is that the difficulties can be reduced when people understand the different forces that persist.

  17. Colony types and virulence traits of Legionella feeleii determined by exopolysaccharide materials.

    Science.gov (United States)

    Wang, Changle; Saito, Mitsumasa; Ogawa, Midori; Yoshida, Shin-Ichi

    2016-05-01

    Legionella feeleii is a Gram-negative pathogenic bacterium that causes Pontiac fever and pneumonia in humans. When L. feeleii serogroup 1 (ATCC 35072) was cultured on BCYE agar plates, two types of colonies were observed and exhibited differences in color, opacity and morphology. Since the two colony types are white rugose and brown translucent, they were termed as white rugose L. feeleii (WRLf) and brown translucent L. feeleii (BTLf), respectively. They exhibited different growth capacities in BYE broth in vitro, and it was found that WRLf could transform to BTLf. Under the electron microscope, it was observed that WRLf secreted materials which could be stained with ruthenium red, which was absent in BTLf. When U937 macrophages and HeLa cells were infected with the bacteria, WRLf manifested stronger internalization ability than BTLf. Intracellular growth in murine macrophages and Acanthamoeba cells was affected by the level of initial phagocytosis. WRLf was more resistant to human serum bactericidal action than BTLf. After being inoculated to guinea pigs, both organisms caused fever in the animals. These results suggest that ruthenium red-stained materials secreted in the surroundings may play a crucial role in determining L. feeleii colony morphology and virulence traits. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Ecological conditions favoring budding in colonial organisms under environmental disturbance.

    Directory of Open Access Journals (Sweden)

    Mayuko Nakamaru

    Full Text Available Dispersal is a topic of great interest in ecology. Many organisms adopt one of two distinct dispersal tactics at reproduction: the production of small offspring that can disperse over long distances (such as seeds and spawned eggs, or budding. The latter is observed in some colonial organisms, such as clonal plants, corals and ants, in which (superorganisms split their body into components of relatively large size that disperse to a short distance. Contrary to the common dispersal viewpoint, short-dispersal colonial organisms often flourish even in environments with frequent disturbances. In this paper, we investigate the conditions that favor budding over long-distance dispersal of small offspring, focusing on the life history of the colony growth and the colony division ratio. These conditions are the relatively high mortality of very small colonies, logistic growth, the ability of dispersers to peacefully seek and settle unoccupied spaces, and small spatial scale of environmental disturbance. If these conditions hold, budding is advantageous even when environmental disturbance is frequent. These results suggest that the demography or life history of the colony underlies the behaviors of the colonial organisms.

  19. Morphodynamics of a growing microbial colony driven by cell death

    Science.gov (United States)

    Ghosh, Pushpita; Levine, Herbert

    2017-11-01

    Bacterial cells can often self-organize into multicellular structures with complex spatiotemporal morphology. In this work, we study the spatiotemporal dynamics of a growing microbial colony in the presence of cell death. We present an individual-based model of nonmotile bacterial cells which grow and proliferate by consuming diffusing nutrients on a semisolid two-dimensional surface. The colony spreads by growth forces and sliding motility of cells and undergoes cell death followed by subsequent disintegration of the dead cells in the medium. We model cell death by considering two possible situations: In one of the cases, cell death occurs in response to the limitation of local nutrients, while the other case corresponds to an active death process, known as apoptotic or programmed cell death. We demonstrate how the colony morphology is influenced by the presence of cell death. Our results show that cell death facilitates transitions from roughly circular to highly branched structures at the periphery of an expanding colony. Interestingly, our results also reveal that for the colonies which are growing in higher initial nutrient concentrations, cell death occurs much earlier compared to the colonies which are growing in lower initial nutrient concentrations. This work provides new insights into the branched patterning of growing bacterial colonies as a consequence of complex interplay among the biochemical and mechanical effects.

  20. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Aladdin, H

    2000-01-01

    This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo....... Significant increase in absolute numbers of circulating CD34+ cells was detected in the treatment group (P = 0.006). The function of progenitor cells was examined in vitro using a colony-forming unit (CFU) assay, and increase in the number of CFU/ml was detected (P = 0.005). In order to estimate the effect...