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  1. Article ; Online: Flow Cytometry Reveals the Nature of Oncotic Cells.

    Vossenkamper, Anna / Warnes, Gary

    International journal of molecular sciences

    2019  Volume 20, Issue 18

    Abstract: The term necrosis is commonly applied to cells that have died via a non-specific pathway or mechanism but strictly is the description of the degradation processes involved once the plasma membrane of the cell has lost integrity. The signalling pathways ... ...

    Abstract The term necrosis is commonly applied to cells that have died via a non-specific pathway or mechanism but strictly is the description of the degradation processes involved once the plasma membrane of the cell has lost integrity. The signalling pathways potentially involved in accidental cell death (ACD) or oncosis are under-studied. In this study, the flow cytometric analysis of the intracellular antigens involved in regulated cell death (RCD) revealed the phenotypic nature of cells undergoing oncosis or necrosis. Sodium azide induced oncosis but also classic apoptosis, which was blocked by zVAD (z-Vla-Ala-Asp(OMe)-fluoromethylketone). Oncotic cells were found to be viability
    MeSH term(s) Apoptosis ; Biomarkers ; Caspases/metabolism ; Flow Cytometry ; Humans ; Immunophenotyping ; Models, Biological ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology
    Chemical Substances Biomarkers ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2019-09-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20184379
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Flow Cytometry Reveals the Nature of Oncotic Cells

    Anna Vossenkamper / Gary Warnes

    International Journal of Molecular Sciences, Vol 20, Iss 18, p

    2019  Volume 4379

    Abstract: The term necrosis is commonly applied to cells that have died via a non-specific pathway or mechanism but strictly is the description of the degradation processes involved once the plasma membrane of the cell has lost integrity. The signalling pathways ... ...

    Abstract The term necrosis is commonly applied to cells that have died via a non-specific pathway or mechanism but strictly is the description of the degradation processes involved once the plasma membrane of the cell has lost integrity. The signalling pathways potentially involved in accidental cell death (ACD) or oncosis are under-studied. In this study, the flow cytometric analysis of the intracellular antigens involved in regulated cell death (RCD) revealed the phenotypic nature of cells undergoing oncosis or necrosis. Sodium azide induced oncosis but also classic apoptosis, which was blocked by zVAD (z-Vla-Ala-Asp(OMe)-fluoromethylketone). Oncotic cells were found to be viability +ve /caspase-3 −ve /RIP3 +ve/−ve (Receptor-interacting serine/threonine protein kinase 3). These two cell populations also displayed a DNA damage response (DDR) phenotype pH2AX +ve /PARP −ve , cleaved PARP induced caspase independent apoptosis H2AX −ve /PARP +ve and hyper-activation or parthanatos H2AX +ve /PARP +ve . Oncotic cells with phenotype cell viability +ve /RIP3 −ve /caspase-3 −ve showed increased DDR and parthanatos. Necrostatin-1 down-regulated DDR in oncotic cells and increased sodium azide induced apoptosis. This flow cytometric approach to cell death research highlights the link between ACD and the RCD processes of programmed apoptosis and necrosis.
    Keywords accidental cell death ; oncosis ; DDR ; parthanatos ; flow cytometry ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Transitional B cells: how well are the checkpoints for specificity understood?

    Vossenkämper, Anna / Spencer, Jo

    Archivum immunologiae et therapiae experimentalis

    2011  Volume 59, Issue 5, Page(s) 379–384

    Abstract: It is crucial for the immune system to minimise the number of circulating mature self-reactive B cells, in order to reduce the potential for the development of autoantibody-related autoimmune diseases. Studies of animal models have identified two major ... ...

    Abstract It is crucial for the immune system to minimise the number of circulating mature self-reactive B cells, in order to reduce the potential for the development of autoantibody-related autoimmune diseases. Studies of animal models have identified two major checkpoints that ensure that such cells do not contribute to the naïve B cell repertoire. The first is in the bone marrow as B cells develop and the second is in the spleen; B cells that are released from the bone marrow as transitional B cells go through more stringent selection in the spleen before they develop into mature naïve B cells. Transitional B cells and their maturation have mostly been studied in mice. However, recent studies characterised human transitional B cells and found considerable differences to current models. In this review, we will consider these differences alongside known differences in mouse and human splenic function and ask whether human transitional B cells might develop along a different pathway.
    MeSH term(s) Animals ; Antigens, Differentiation, B-Lymphocyte/immunology ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Autoimmunity/immunology ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; Bone Marrow/metabolism ; Cell Differentiation/immunology ; Humans ; Mice ; Models, Biological ; Precursor Cells, B-Lymphoid/immunology ; Precursor Cells, B-Lymphoid/metabolism ; Signal Transduction ; Spleen/immunology ; Spleen/metabolism
    Chemical Substances Antigens, Differentiation, B-Lymphocyte
    Language English
    Publishing date 2011-07-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282209-x
    ISSN 1661-4917 ; 0004-069X
    ISSN (online) 1661-4917
    ISSN 0004-069X
    DOI 10.1007/s00005-011-0135-0
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    In stock of ZB MED Cologne/Königswinter

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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  4. Article ; Online: Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.

    Roberts, Kevin J / Cubitt, Marion F / Carlton, Timothy M / Rodrigues-Duarte, Lurdes / Maggiore, Luana / Chai, Ray / Clare, Simon / Harcourt, Katherine / MacDonald, Thomas T / Ray, Keith P / Vossenkämper, Anna / West, Michael R / Crowe, J Scott

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 19422

    Abstract: Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn's disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised ... ...

    Abstract Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn's disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies.
    MeSH term(s) Animals ; Antibodies, Bispecific/administration & dosage ; Antibodies, Bispecific/pharmacology ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacology ; Drug Evaluation, Preclinical/methods ; Female ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Interleukin-23/immunology ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/immunology
    Chemical Substances Antibodies, Bispecific ; Antibodies, Monoclonal ; Interleukin-23 ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2021-09-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-97236-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Online ; Thesis: Neutralisation von Interleukin-18 zur Therapie einer überschiessenden Th1-Immunreaktion nach oraler Infektion mit Toxoplasma gondii im Mausmodell

    Vossenkämper, Anna

    2005  

    Author's details vorgelegt von Anna Vossenkämper
    Language German
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Freie Univ., Diss--Berlin, 2005
    Note Dateiformat: zip, Dateien im PDF-Format
    Database Former special subject collection: coastal and deep sea fishing

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  6. Book ; Online ; Thesis: Neutralisation von Interleukin-18 zur Therapie einer überschiessenden Th1-Immunreaktion nach oraler Infektion mit Toxoplasma gondii im Mausmodell

    Vossenkämper, Anna [Verfasser]

    2005  

    Author's details vorgelegt von Anna Vossenkämper
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  7. Article ; Online: Always one step ahead: How pathogenic bacteria use the type III secretion system to manipulate the intestinal mucosal immune system.

    Vossenkämper, Anna / Macdonald, Thomas T / Marchès, Olivier

    Journal of inflammation (London, England)

    2011  Volume 8, Page(s) 11

    Abstract: The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to tolerate ... ...

    Abstract The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to tolerate commensal bacteria and food antigens. Intestinal pathogens have developed strategies to regulate intestinal immunity and inflammation in order to establish or prolong infection. The organisms that employ a type III secretion system use a molecular syringe to deliver effector proteins into the cytoplasm of host cells. These effectors target the host cell cytoskeleton, cell organelles and signaling pathways. This review addresses the multiple mechanisms by which the type III secretion system targets the intestinal immune response, with a special focus on pathogenic E. coli.
    Language English
    Publishing date 2011-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2164385-4
    ISSN 1476-9255 ; 1476-9255
    ISSN (online) 1476-9255
    ISSN 1476-9255
    DOI 10.1186/1476-9255-8-11
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  8. Article ; Online: Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease

    Kevin J. Roberts / Marion F. Cubitt / Timothy M. Carlton / Lurdes Rodrigues-Duarte / Luana Maggiore / Ray Chai / Simon Clare / Katherine Harcourt / Thomas T. MacDonald / Keith P. Ray / Anna Vossenkämper / Michael R. West / J. Scott Crowe

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Abstract Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn’s disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, ... ...

    Abstract Abstract Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn’s disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Always one step ahead

    Marchès Olivier / MacDonald Thomas T / Vossenkämper Anna

    Journal of Inflammation, Vol 8, Iss 1, p

    How pathogenic bacteria use the type III secretion system to manipulate the intestinal mucosal immune system

    2011  Volume 11

    Abstract: Abstract The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to ... ...

    Abstract Abstract The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to tolerate commensal bacteria and food antigens. Intestinal pathogens have developed strategies to regulate intestinal immunity and inflammation in order to establish or prolong infection. The organisms that employ a type III secretion system use a molecular syringe to deliver effector proteins into the cytoplasm of host cells. These effectors target the host cell cytoskeleton, cell organelles and signaling pathways. This review addresses the multiple mechanisms by which the type III secretion system targets the intestinal immune response, with a special focus on pathogenic E. coli .
    Keywords gut-associated lymphoid tissue ; type 3 secretion system ; EPEC ; Shigella ; Pathology ; RB1-214 ; Medicine ; R ; DOAJ:Pathology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 570
    Language English
    Publishing date 2011-05-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease.

    Crowe, J Scott / Roberts, Kevin J / Carlton, Timothy M / Maggiore, Luana / Cubitt, Marion F / Clare, Simon / Harcourt, Katherine / Reckless, Jill / MacDonald, Thomas T / Ray, Keith P / Vossenkämper, Anna / West, Michael R

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 4941

    Abstract: TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 ... ...

    Abstract TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.
    MeSH term(s) Administration, Oral ; Animals ; Biomarkers/blood ; Colon/metabolism ; Colon/pathology ; Cytokines/blood ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Ileum/metabolism ; Ileum/pathology ; Inflammatory Bowel Diseases/blood ; Inflammatory Bowel Diseases/chemically induced ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/pathology ; Infliximab/pharmacokinetics ; Infliximab/pharmacology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Mice ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/blood
    Chemical Substances Biomarkers ; Cytokines ; Tumor Necrosis Factor-alpha ; Infliximab (B72HH48FLU)
    Language English
    Publishing date 2018-03-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-23277-7
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