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  1. Book ; Audio / Video: Internetpräsentationen für Architekten und Freiberufler

    Büscher, Dirk

    [Leistungsbild, rechtliche Rahmenbedingungen und Marketingstrategien für Architekturbüros, insbesondere im Hinblick auf die Präsentation im Internet]

    (Wissenschaft auf CD-ROM)

    2001  

    Author's details von Dirk Büscher
    Series title Wissenschaft auf CD-ROM
    Keywords Architektenbüro ; Web Site ; Online-Marketing
    Language German
    Size 1 CD-ROM, 12 cm
    Edition [Elektronische Ressource]
    Publisher Tectum-Verl
    Publishing place Marburg
    Document type Book ; Audio / Video
    ISBN 3828850766 ; 9783828850767
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  2. Book ; Thesis: Die qualifizierte faktische Konzernierung - eine gelungene Fortbildung des Rechts der GmbH?

    Büscher, Dirk

    (Europäische Hochschulschriften : Reihe 2, Rechtswissenschaft ; 2632)

    1999  

    Author's details Dirk Büscher
    Series title Europäische Hochschulschriften : Reihe 2, Rechtswissenschaft ; 2632
    Keywords Qualifizierter faktischer Konzern ; Haftung ; GmbH ; Deutschland
    Language German
    Size XXV, 202 S, 21 cm
    Publisher Lang
    Publishing place Frankfurt am Main u.a.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Bochum, 1998
    ISBN 363134726X ; 9783631347263
    Database Former special subject collection: coastal and deep sea fishing

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  3. Book ; Thesis: Untersuchungen zur Rolle der zytosolischen Serin/Threonin-Kinase Raf-1 in der Makrophagenzellinie BAC-1.2F5

    Büscher, Dirk

    1994  

    Author's details von Dirk Büscher
    Language German
    Size 71, [14] S, Ill., graph. Darst
    Edition [Mikrofiche-Ausg.]
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Hannover, 1994
    Note Mikrofiche-Ausg.: 1 Mikrofiche : 24x
    Database Former special subject collection: coastal and deep sea fishing

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  4. Book ; Thesis: Untersuchungen zur Rolle der zytosolischen Serin/Threonin-Kinase Raf-1 in der Makrophagenzellinie BAC-1.2F5

    Büscher, Dirk

    1994  

    Author's details von Dirk Büscher
    Language German
    Size 71 Bl., Anh
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Hannover, 1994
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  5. Article: GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2

    Mizrahi, Rena A. / Lin, Wendy Y. / Gras, Ashley / Niedecken, Ariel R. / Wagner, Ellen K. / Keating, Sheila M. / Ikon, Nikita / Manickam, Vishal A. / Asensio, Michael A. / Leong, Jackson / Medina-Cucurella, Angelica V. / Benzie, Emily / Carter, Kyle P. / Chiang, Yao / Edgar, Robert C. / Leong, Renee / Lim, Yoong Wearn / Simons, Jan Fredrik / Spindler, Matthew J. /
    Stadtmiller, Kacy / Wayham, Nicholas / Büscher, Dirk / Terencio, Jose Vicente / Germanio, Clara Di / Chamow, Steven M. / Olson, Charles / Pino, Paula A. / Park, Jun-Gyu / Hicks, Amberlee / Ye, Chengjin / Garcia-Vilanova, Andreu / Martinez-Sobrido, Luis / Torrelles, Jordi B. / Johnson, David S. / Adler, Adam S.

    Pathogens. 2022 July 19, v. 11, no. 7

    2022  

    Abstract: Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope ... ...

    Abstract Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; cell growth ; cell lines ; drugs ; epitopes ; half life ; humans ; immunoglobulin G ; microfluidic technology ; models ; monoclonal antibodies ; neutralization ; pharmacokinetics ; product quality ; sequence diversity ; therapeutics ; toxicology ; viruses
    Language English
    Dates of publication 2022-0719
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11070806
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Biodistribution and Efficacy of Human Adipose-Derived Mesenchymal Stem Cells Following Intranodal Administration in Experimental Colitis.

    Lopez-Santalla, Mercedes / Mancheño-Corvo, Pablo / Escolano, Amelia / Menta, Ramon / DelaRosa, Olga / Abad, Jose Luis / Büscher, Dirk / Redondo, Juan M / Bueren, Juan A / Dalemans, Wilfried / Lombardo, Eleuterio / Garin, Marina I

    Frontiers in immunology

    2017  Volume 8, Page(s) 638

    Abstract: Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC ... ...

    Abstract Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs). This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response. Intranodal (IN), also referred as intralymphatic, injection of cells, like dendritic cells, is being proposed in the clinic for the treatment of cancer and allergy, showing that this route of administration is clinically safe and efficient. In this study, we investigated, for the first time, the biodistribution and the efficacy of Luciferase
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.00638
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Intralymphatic Administration of Adipose Mesenchymal Stem Cells Reduces the Severity of Collagen-Induced Experimental Arthritis.

    Mancheño-Corvo, Pablo / Lopez-Santalla, Mercedes / Menta, Ramon / DelaRosa, Olga / Mulero, Francisca / Del Rio, Borja / Ramirez, Cristina / Büscher, Dirk / Bueren, Juan A / Lopez-Belmonte, Juan / Dalemans, Wilfried / Garin, Marina I / Lombardo, Eleuterio

    Frontiers in immunology

    2017  Volume 8, Page(s) 462

    Abstract: Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Previous studies have demonstrated that ...

    Abstract Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Previous studies have demonstrated that MSCs, administered systemically, migrate to lymphoid tissues associated with the inflammatory site where functional MSC-induced immune cells with a regulatory phenotype were increased mediating the immunomodulatory effects of MSCs. These results suggest that homing of MSCs to the lymphatic system plays an important role in the mechanism of action of MSCs
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.00462
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis.

    Martín Arranz, Eduardo / Martín Arranz, María Dolores / Robredo, Tomás / Mancheño-Corvo, Pablo / Menta, Ramón / Alves, Francisco Javier / Suárez de Parga, Jose Manuel / Mora Sanz, Pedro / de la Rosa, Olga / Büscher, Dirk / Lombardo, Eleuterio / de Miguel, Fernando

    Stem cell research & therapy

    2018  Volume 9, Issue 1, Page(s) 95

    Abstract: Background: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived ... ...

    Abstract Background: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats.
    Methods: Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (10
    Results: Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (- 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (- 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment.
    Conclusions: ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis.
    MeSH term(s) Adipose Tissue/cytology ; Animals ; Cells, Cultured ; Colitis, Ulcerative/etiology ; Colitis, Ulcerative/pathology ; Colitis, Ulcerative/therapy ; Constriction, Pathologic ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Rats ; Rats, Sprague-Dawley ; Trinitrobenzenesulfonic Acid/toxicity
    Chemical Substances Trinitrobenzenesulfonic Acid (8T3HQG2ZC4)
    Language English
    Publishing date 2018-04-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-018-0837-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Toll-like receptor-mediated signaling in human adipose-derived stem cells: implications for immunogenicity and immunosuppressive potential.

    Lombardo, Eleuterio / DelaRosa, Olga / Mancheño-Corvo, Pablo / Menta, Ramón / Ramírez, Cristina / Büscher, Dirk

    Tissue engineering. Part A

    2009  Volume 15, Issue 7, Page(s) 1579–1589

    Abstract: Human adipose-derived stem cells (hASCs) are mesenchymal stem cells with reduced immunogenicity and the capability to modulate immune responses. These properties make hASCs of special interest as therapeutic agents in the settings of chronic inflammatory ...

    Abstract Human adipose-derived stem cells (hASCs) are mesenchymal stem cells with reduced immunogenicity and the capability to modulate immune responses. These properties make hASCs of special interest as therapeutic agents in the settings of chronic inflammatory and autoimmune diseases. Exogenous and endogenous toll-like receptor (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis because of the permanent exposure of the immune system to TLR-specific stimuli. Therefore, hASCs employed in therapy are potentially exposed to TLR ligands, which may result in the modulation of hASC activity and therapeutic potency. In this study, we demonstrate that hASCs possess active TLR2, TLR3, and TLR4, because activation with specific ligands resulted in induction of nuclear factor kappa B-dependent genes, such as manganese superoxide dismutase and the release of interleukin (IL)-6 and IL-8. TLR3 and TLR4 ligands increased osteogenic differentiation, but no effect on adipogenic differentiation or proliferation was observed. Moreover, we show that TLR activation does not impair the immunogenic and immunosuppressive properties of hASCs. These results may have important implications with respect to the safety and efficacy of hASC-based cell therapies.
    MeSH term(s) Adipocytes/cytology ; Adult ; Cell Differentiation ; Cell Proliferation ; Female ; Gene Expression Regulation ; Humans ; Immune Tolerance/immunology ; Immunologic Factors/metabolism ; Ligands ; Male ; Phenotype ; Signal Transduction ; Stem Cells/cytology ; Stem Cells/immunology ; Toll-Like Receptors/genetics ; Toll-Like Receptors/metabolism
    Chemical Substances Immunologic Factors ; Ligands ; Toll-Like Receptors
    Language English
    Publishing date 2009-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.tea.2008.0340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses.

    González, Manuel A / Gonzalez-Rey, Elena / Rico, Laura / Büscher, Dirk / Delgado, Mario

    Gastroenterology

    2009  Volume 136, Issue 3, Page(s) 978–989

    Abstract: Background & aims: Crohn's disease is a chronic disease characterized by severe T-helper (Th)1 cell-driven inflammation of the colon partially caused by a loss of immune tolerance against mucosal antigens. Mesenchymal stem cells were recently described ... ...

    Abstract Background & aims: Crohn's disease is a chronic disease characterized by severe T-helper (Th)1 cell-driven inflammation of the colon partially caused by a loss of immune tolerance against mucosal antigens. Mesenchymal stem cells were recently described to suppress effector T-cell responses and have therapeutic effects in some immune disorders. Here, we investigated the potential therapeutic effects of human adipose-derived mesenchymal stem cells (hASCs) in a model of inflammatory bowel disease.
    Methods: Mice with trinitrobenzene sulfonic acid-induced colitis were treated with hASCs after onset of disease and clinical scores were evaluated. Inflammatory response was determined by measuring the levels of different inflammatory mediators in colon and serum. Th1-mediated effector responses were evaluated by determining the proliferation and cytokine profile of activated mesenteric lymph node cells. The number of regulatory T cells and the suppressive capacity on Th1 cell responses was determined.
    Results: Systemic infusion of hASCs or murine ASCs ameliorated the clinical and histopathologic severity of colitis, abrogating body weight loss, diarrhea, and inflammation and increasing survival (P < .001). This therapeutic effect was mediated by down-regulating both Th1-driven autoimmune and inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin-10 levels (P < .001), directly acting on activated macrophages. hASCs also impaired Th1 cell expansion and induced/activated CD4(+)CD25(+)FoxP3(+) regulatory T cells with suppressive capacity on Th1 effector responses in vitro and in vivo (P < .001).
    Conclusions: hASCs emerge as key regulators of immune tolerance and as attractive candidates for a cell-based therapy for Crohn's disease.
    MeSH term(s) Adipose Tissue/cytology ; Animals ; Autoimmunity ; Cells, Cultured ; Colitis/immunology ; Colitis/pathology ; Colitis/therapy ; Crohn Disease/immunology ; Crohn Disease/pathology ; Crohn Disease/therapy ; Disease Models, Animal ; Down-Regulation/immunology ; Humans ; Immune Tolerance ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology
    Language English
    Publishing date 2009-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2008.11.041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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