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327 results on '"Ramsay, Alistair"'

51. The efficacy of cidofovir treatment of mice infected with ectromelia (mousepox) virus encoding interleukin-4

Author

Robbins, S, Jackson, Ronald, Fenner, Frank, Beaton, S, Medveczky, C, Ramshaw, Ian, Ramsay, Alistair, Robbins, S, Jackson, Ronald, Fenner, Frank, Beaton, S, Medveczky, C, Ramshaw, Ian, and Ramsay, Alistair

Abstract

Improved vaccines and therapies for virulent poxvirus infection are required, particularly in the light of recent threats of bioterrorism. Cidofovir (HPMPC) is an acyclic nucleoside analog with proven efficacy against poxviruses. Here, we evaluated HPMPC

Published
2005

62. Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice

Author

Lees, Catherine, Apostolopoulos, Vasso, Acres, Bruce, Ramshaw, Ian, Ramsay, Alistair, Ong, Cheng Soon, McKenzie, Ian F C, Lees, Catherine, Apostolopoulos, Vasso, Acres, Bruce, Ramshaw, Ian, Ramsay, Alistair, Ong, Cheng Soon, and McKenzie, Ian F C

Published
2000

65. The effect of IL-5 eotaxin expression in the lung on eosinophil traffickling and degranulation and the induction of bronchial hyperreactivity

Author

Mould, A, Ramsay, Alistair, Matthaei, Klaus, Young, I M, Rothenberg, Marc E, Foster, Paul S, Mould, A, Ramsay, Alistair, Matthaei, Klaus, Young, I M, Rothenberg, Marc E, and Foster, Paul S

Abstract

The mechanisms regulating the selective migration and degranulation of eosinophils in the asthmatic lung and the subsequent development of airways hyperreactivity (AHR) have not been fully delineated. In this investigation, we have employed a novel transgene model to facilitate the dissection of the contributions of IL-5 and/or eotaxin to eosinophil function in the absence of complex tissue signals derived from the allergic lung. Gene transfer of IL-5 and/or eotaxin to the lungs of naive mice induced a pronounced and selective airways eosinophilia, but did not result in eosinophil degranulation or AHR. Airways eosinophilia occurred independently of the induction of a blood eosinophilia, but was markedly augmented by the coexpression of both cytokines and/or by the transient mobilization of eosinophils from the bone marrow by the administration of i.v. IL-5. However, for eosinophil degranulation and AHR to occur, the inhalation of Ag was required in association with IL-5 and eotaxin expression. Investigations in IL-5- deficient mice linked eosinophilia, and not solely IL-5 and eotaxin, with the induction of AHR. Furthermore, eosinophil degranulation and AHR were dependent on CD4+ T cells. Importantly, this investigation shows that IL-5 regulates eosinophilia within the lung as well as in the circulation and also amplifies eotaxin-induced chemotaxis in the airway compartment. Moreover, the interplay between these cytokines, CD4+ T cells, and factors generated by Ag inhalation provides fundamental signals for eosinophil degranulation and the induction of AHR.

Published
2000

66. Recombinant adenovirus vectors expressing interleukin-5 and -6 specifically enhance mucosal immunoglobulin A responses in the lung

Author

Braciak, Todd, Gallichan, W, Graham, F L, Richards, C, Ramsay, Alistair, Rosenthal, K, Gauldie, J, Braciak, Todd, Gallichan, W, Graham, F L, Richards, C, Ramsay, Alistair, Rosenthal, K, and Gauldie, J

Abstract

In this study, we have examined the in vivo effects of interleukin-5 (IL-5) and IL-6 over-expression on systemic and mucosal immune responses using recombinant human type 5 adenoviruses capable of expressing these cytokines upon infection. A recombinant adenovirus containing the murine IL-5 gene within the E3 region was constructed and found to express high levels of IL-5 protein both in vitro and in vivo. Intranasal inoculation of mice with this vector or a vector expressing murine IL-6 increased adenovirus-specific immunoglobulin A (IgA) titres in lung lavage fluid threefold compared with those elicited by control virus. The simultaneous expression of both cytokines by co-inoculation altered the kinetics of the mucosal anti-adenovirus IgA response and resulted in a more than additive increase in antibody titres. The co-expression effect on IgA synthesis was not due to an increase in numbers of antigen-specific resident lung tissue lymphocytes. When mucosal IgG responses were examined, IL-6 expression had the largest impact on anti-adenovirus levels, whereas co-expression produced an intermediate response. Systemic immune responses were also affected by IL-6 expression as a twofold increase in serum IgG anti-adenovirus titres was observed after a secondary challenge with wild-type adenovirus. These results demonstrate a relevant role for IL-5 and IL-6 in the development of mucosal immune responses in vivo and suggest that the incorporation of either IL-5 and/or IL-6 into recombinant adenovirus vectors may be a useful tool in the development of mucosal vaccines.

Published
2000

67. PARP inhibition by olaparib or gene knockout blocks asthma-like manifestation in mice by modulating CD4+ T cell function.

Author

Ghonim, Mohamed A., Pyakurel, Kusma, Ibba, Salome V., Al-Khami, Amir A., Wang, Jefrey, Rodriguez, Paulo, Rady, Hamada F., El-Bahrawy, Ali H., Lammi, Matthew R., Mansy, Moselhy S., Al-Ghareeb, Kamel, Ramsay, Alistair, Ochoa, Augusto, Naura, Amarjit S., and Boulares, A. Hamid

Subjects
ASTHMATICS, T cells, OVALBUMINS, ASTHMA, CYTOKINES, CHEMOKINES
Abstract

Background: An important portion of asthmatics do not respond to current therapies. Thus, the need for new therapeutic drugs is urgent. We have demonstrated a critical role for PARP in experimental asthma. Olaparib, a PARP inhibitor, was recently introduced in clinical trials against cancer. The objective of the present study was to examine the efficacy of olaparib in blocking established allergic airway inflammation and hyperresponsiveness similar to those observed in human asthma in animal models of the disease. Methods: We used ovalbumin (OVA)-based mouse models of asthma and primary CD4+ T cells. C57BL/6J WT or PARP-1-/- mice were subjected to OVA sensitization followed by a single or multiple challenges to aerosolized OVA or left unchallenged. WT mice were administered, i.p., 1 mg/kg, 5 or 10 mg/kg of olaparib or saline 30 min after each OVA challenge. Results: Administration of olaparib in mice 30 min post-challenge promoted a robust reduction in airway eosinophilia, mucus production and hyperresponsiveness even after repeated challenges with ovalbumin. The protective effects of olaparib were linked to a suppression of Th2 cytokines eotaxin, IL-4, IL-5, IL-6, IL-13, and M-CSF, and ovalbumin- specific IgE with an increase in the Th1 cytokine IFN-γ. These traits were associated with a decrease in splenic CD4+ T cells and concomitant increase in T-regulatory cells. The aforementioned traits conferred by olaparib administration were consistent with those observed in OVA-challenged PARP-1-/- mice. Adoptive transfer of Th2-skewed OTII- WT CD4+ T cells reversed the Th2 cytokines IL-4, IL-5, and IL-10, the chemokine GM-CSF, the Th1 cytokines IL-2 and IFN-γ, and ovalbumin-specific IgE production in ovalbumin-challenged PARP-1-/-mice suggesting a role for PARP-1 in CD4+ T but not B cells. In ex vivo studies, PARP inhibition by olaparib or PARP-1 gene knockout markedly reduced CD3/CD28-stimulated gata-3 and il4 expression in Th2-skewed CD4+ T cells while causing a moderate elevation in t-bet and IFN-γ expression in Th1-skewed CD4+ T cells. Conclusions: Our findings show the potential of PARP inhibition as a viable therapeutic strategy and olaparib as a likely candidate to be tested in human asthma clinical trials. [ABSTRACT FROM AUTHOR]

Published
2015
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68. Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity

Author

Ramsay, Alistair, Kent, Stephen J, Strugnell, R, Suhrbier, A, Thomson, Scott, Ramshaw, Ian, Ramsay, Alistair, Kent, Stephen J, Strugnell, R, Suhrbier, A, Thomson, Scott, and Ramshaw, Ian

Abstract

In this article, we describe several novel genetic vaccination strategies designed to facilitate the development of different types of immune responses. These include: i) the consecutive use of DNA and fowlpoxvirus vectors in 'prime-boost' strategies which induce greatly enhanced and sustained levels of both cell-mediated immunity and humoral immunity, including mucosal responses; ii) the co-expression of genes encoding cytokines and cell-surface receptors, and the use of immunogenic carrier molecules, for immune modulation and/or improved targeting of vector-expressed vaccine antigens; and iii) the expression of minimal immunogenic amino acid sequences, particularly cytotoxic CD8+ T-cell determinants, in 'polytope' vector vaccines. The capacity to modulate and enhance specific immune responses by the use of approaches such as these may underpin the development of vaccines against diseases for which no effective strategies are currently available.

Published
1999

74. Interleukin-17

Author

Kolls, Jay K., primary, Kanaly, Suzanne T., additional, and Ramsay, Alistair J., additional

Published
2003
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83. IL-5-Deficient Mice Have a Developmental Defect in CD5+ B-1 Cells and Lack Eosinophilia but Have Normal Antibody and Cytotoxic T Cell Responses

Author

Kopf, Manfred, primary, Brombacher, Frank, additional, Hodgkin, Philip D, additional, Ramsay, Alistair J, additional, Milbourne, Elizabeth A, additional, Dai, Wen J, additional, Ovington, Karen S, additional, Behm, Carolyn A, additional, Köhler, Georges, additional, Young, Ian G, additional, and Matthaei, Klaus I, additional

Published
1996
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92. CD4+ T cell-independent DNA vaccination against opportunistic infections.

Author

Mingquan Zheng, Ramsay, Alistair J., Robichaux, Myles B., Norris, Karen A., Kliment, Corrine, Crowe, Christopher, Rapaka, Rekha R., Steele, Chad, McAllister, Florencia, Shellito, Judd E., Marrero, Luis, Schwarzenberger, Paul, Qiu Zhong, and Kolls, Jay K.

Subjects
*OPPORTUNISTIC infections, *CD4 antigen, *VACCINATION, *T cells, *PREVENTION of communicable diseases, *IMMUNOGLOBULINS
Abstract

Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell-independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modifed DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens. [ABSTRACT FROM AUTHOR]

Published
2005
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93. Raw material gains erode Chinese mill margins in Jan.

Author

Lim, Paul, Ramsay, Alistair, and Pan, Zihuan

Subjects
RAW materials, INDUSTRIAL costs, COKING coal, SUPPLY chains, IRON ores
Abstract

Fastmarkets' Ferrous Analytics report helps subscribers keep track of hot metal costs and steel production spreads in China, along with key pricing components of the steelmaking raw materials supply chain in Asia. [ABSTRACT FROM AUTHOR]

Published
2022

98. Chinese mill margins recover in December; scrap now commands premium over hot metal.

Author

Lim, Paul, Ramsay, Alistair, Fan, Jane, and Pan, Zihuan

Subjects
METALS, INDUSTRIAL costs, RAW materials, COKING coal, SUPPLY chains
Abstract

Fastmarkets' Ferrous Analytics report helps subscribers keep track of hot metal costs and steel production spreads in China, along with key pricing components of the steelmaking raw materials supply chain in Asia. [ABSTRACT FROM AUTHOR]

Published
2022

99. China steelmaking margins narrow on lower steel prices in Nov.

Author

Lim, Paul, Ramsay, Alistair, and Fan, Jane

Subjects
STEEL prices, STEEL manufacture, COKING coal, IRON ores
Abstract

China, steel, iron ore, coking coal, hot rolled coil, rebar, steel scrap, ferrous scrap, billet Keywords: China; steel; iron ore; coking coal; hot rolled coil; rebar; steel scrap; ferrous scrap; billet EN China steel iron ore coking coal hot rolled coil rebar steel scrap ferrous scrap billet N.PAG N.PAG 1 01/03/22 20220103 NES 220103 Fastmarkets' Ferrous Analytics report helps subscribers keep track of hot metal costs and steel production spreads in China, along with key pricing components of the steelmaking raw materials supply chain in Asia. [Extracted from the article]

Published
2022

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