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Book ; Online ; Thesis: Autoantikörper bei neuroimmunologischen Erkrankungen und ihre Rolle bei der Krankheitspathogenese und während der Schwangerschaft

Mader, Simone [Verfasser]

2022

Author's details	Simone Mader
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Universitätsbibliothek der Ludwig-Maximilians-Universität
Publishing place	München
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Editorial: Insights in inflammation: 2022.

Ghezzi, Pietro / Lucas, Rudolf / Mader, Simone / Miossec, Pierre / Sacre, Sandra

Frontiers in immunology

2023 Volume 14, Page(s) 1224343

MeSH term(s)	Humans ; Inflammation
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1224343
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis.

Boldrini, Vinícius Oliveira / Mader, Simone / Kümpfel, Tania / Meinl, Edgar

Multiple sclerosis and related disorders

2023 Volume 75, Page(s) 104733

Abstract: Ublituximab, an intravenous glycoengineered chimeric anti-CD20 IgG1 monoclonal antibody (mAb), is a new FDA-approved treatment for relapsing forms of Multiple Sclerosis (MS). Reassembling the other three anti-CD20 mAbs already in use for MS (rituximab, ... ...

Abstract	Ublituximab, an intravenous glycoengineered chimeric anti-CD20 IgG1 monoclonal antibody (mAb), is a new FDA-approved treatment for relapsing forms of Multiple Sclerosis (MS). Reassembling the other three anti-CD20 mAbs already in use for MS (rituximab, ocrelizumab and ofatumumab), ublituximab leads to depletion of B cells but spars long-lived plasma cells. Here, we discuss the main findings obtained during the phase 3 clinical trials (ULTIMATE I and II) for ublituximab versus teriflunomide. The current emergence and approval of new anti-CD20 mAbs with different dose regimens, routes of application, glycoengineering and mechanisms of action may contribute to different clinical outcomes.
MeSH term(s)	Humans ; Multiple Sclerosis/drug therapy ; Antigens, CD20 ; Antibodies, Monoclonal/therapeutic use ; Rituximab/therapeutic use ; Antineoplastic Agents/therapeutic use
Chemical Substances	ublituximab (U59UGK3IPC) ; Antigens, CD20 ; Antibodies, Monoclonal ; Rituximab (4F4X42SYQ6) ; Antineoplastic Agents
Language	English
Publishing date	2023-04-25
Publishing country	Netherlands
Document type	Letter
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2023.104733
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Article ; Online: Pathomechanisms in demyelination and astrocytopathy: autoantibodies to AQP4, MOG, GFAP, GRP78 and beyond.

Mader, Simone / Kümpfel, Tania / Meinl, Edgar

Current opinion in neurology

2022 Volume 35, Issue 3, Page(s) 427–435

Abstract: Purpose of review: The purpose of this review is to highlight the recently emerging pathomechanisms of diseases associated with autoantibodies to AQP4, MOG, GFAP, GRP78 and further novel targets. We discuss novel biomarkers and therapeutic approaches.!## ...

Abstract	Purpose of review: The purpose of this review is to highlight the recently emerging pathomechanisms of diseases associated with autoantibodies to AQP4, MOG, GFAP, GRP78 and further novel targets. We discuss novel biomarkers and therapeutic approaches. Recent findings: Although complement-mediated cytotoxicity (CDC) is regarded as the major effector mechanism for AQP4-IgG in neuromyelitis optica spectrum disorders (NMOSD), recent studies helped to understand the relevance of complement-independent effector mechanisms. For MOG-IgG mediated diseases the role of CDC is less clear. MOG-IgG may trigger a tightly controlled FcR and BTK-driven microglia proliferative response in MOG-antibody-associated diseases. Differences of antibody-mediated tissue damage may reflect differential response to therapy. In addition, antibodies to GFAP, GRP78 and further novel targets have been implicated in demyelination and astrocytopathy. Summary: Elucidating the whole spectrum of effector functions in diseases mediated by AQP4-IgG and MOG-IgG and understanding the role of additional novel autoantibodies involved in demyelination and astrocytopathy may guide further novel treatment decisions.
MeSH term(s)	Aquaporin 4 ; Autoantibodies ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Immunoglobulin G ; Neuromyelitis Optica
Chemical Substances	Aquaporin 4 ; Autoantibodies ; Endoplasmic Reticulum Chaperone BiP ; Immunoglobulin G
Language	English
Publishing date	2022-06-21
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000001052
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Article: Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease.

Mader, Simone / Brimberg, Lior

Cells

2019 Volume 8, Issue 2

Abstract: Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in ... ...

Abstract	Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer's disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.
MeSH term(s)	Animals ; Aquaporin 4/metabolism ; Brain/embryology ; Brain/metabolism ; Disease ; Embryonic Development ; Glymphatic System/metabolism ; Health ; Humans
Chemical Substances	Aquaporin 4
Language	English
Publishing date	2019-01-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8020090
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Article ; Online: MOG-IgG-Associated Bilateral Optic Neuritis in Temporal Relation to Monkeypox Vaccination.

Engels, Daniel / Mader, Simone / Förderreuther, Stefanie / Reindl, Markus / Havla, Joachim / Meinl, Edgar / Kümpfel, Tania / Gerdes, Lisa Ann

Annals of neurology

2023 Volume 93, Issue 6, Page(s) 1216–1217

MeSH term(s)	Humans ; Smallpox Vaccine ; Optic Neuritis ; Myelin-Oligodendrocyte Glycoprotein ; Immunoglobulin G ; Autoantibodies ; Aquaporin 4
Chemical Substances	Smallpox Vaccine ; Myelin-Oligodendrocyte Glycoprotein ; Immunoglobulin G ; Autoantibodies ; Aquaporin 4
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26664
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Article ; Online: Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease

Simone Mader / Lior Brimberg

Cells, Vol 8, Iss 2, p

2019 Volume 90

Abstract	Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer’s disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.
Keywords	aquaporin-4 ; autoantibodies ; disease ; development ; neuromyelitis optica spectrum disorder ; glymphatic system ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Disulfiram and dithiocarbamate analogues demonstrate promising antischistosomal effects.

Rennar, Georg A / Gallinger, Tom L / Mäder, Patrick / Lange-Grünweller, Kerstin / Haeberlein, Simone / Grünweller, Arnold / Grevelding, Christoph G / Schlitzer, Martin

European journal of medicinal chemistry

2022 Volume 242, Page(s) 114641

Abstract: Schistosomiasis is a neglected tropical disease with more than 200 million new infections per year. It is caused by parasites of the genus Schistosoma and can lead to death if left untreated. Currently, only two drugs are available to combat ... ...

Abstract	Schistosomiasis is a neglected tropical disease with more than 200 million new infections per year. It is caused by parasites of the genus Schistosoma and can lead to death if left untreated. Currently, only two drugs are available to combat schistosomiasis: praziquantel and, to a limited extent, oxamniquine. However, the intensive use of these two drugs leads to an increased probability of the emergence of resistance. Thus, the search for new active substances and their targeted development are mandatory. In this study the substance class of "dithiocarbamates" and their potential as antischistosomal agents is highlighted. These compounds are derived from the basic structure of the human aldehyde dehydrogenase inhibitor disulfiram (tetraethylthiuram disulfide, DSF) and its metabolites. Our compounds revealed promising activity (in vitro) against adults of Schistosoma mansoni, such as the reduction of egg production, pairing stability, vitality, and motility. Moreover, tegument damage as well as gut dilatations or even the death of the parasite were observed. We performed detailed structure-activity relationship studies on both sides of the dithiocarbamate core leading to a library of approximately 300 derivatives (116 derivatives shown here). Starting with 100 μm we improved antischistosomal activity down to 25 μm by substitution of the single bonded sulfur atom for example with different benzyl moieties and integration of the two residues on the nitrogen atom into a cyclic structure like piperazine. Its derivatization at the 4-nitrogen with a sulfonyl group or an acyl group led to the most active derivatives of this study which were active at 10 μm. In light of this SAR study, we identified 17 derivatives that significantly reduced motility and induced several other phenotypes at 25 μm, and importantly five of them have antischistosomal activity also at 10 μm. These derivatives were found to be non-cytotoxic in two human cell lines at 100 μm. Therefore, dithiocarbamates seem to be interesting new candidates for further antischistosomal drug development.
MeSH term(s)	Adult ; Aldehyde Dehydrogenase/pharmacology ; Animals ; Disulfiram/pharmacology ; Humans ; Neglected Diseases ; Nitrogen/pharmacology ; Oxamniquine/chemistry ; Oxamniquine/pharmacology ; Piperazines/pharmacology ; Praziquantel/pharmacology ; Schistosoma mansoni ; Schistosomiasis/drug therapy ; Schistosomicides/pharmacology ; Sulfur/pharmacology
Chemical Substances	Piperazines ; Schistosomicides ; Oxamniquine (0O977R722D) ; Praziquantel (6490C9U457) ; Sulfur (70FD1KFU70) ; Aldehyde Dehydrogenase (EC 1.2.1.3) ; Nitrogen (N762921K75) ; Disulfiram (TR3MLJ1UAI)
Language	English
Publishing date	2022-08-18
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2022.114641
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Article ; Online: Novel insights into pathophysiology and therapeutic possibilities reveal further differences between AQP4-IgG- and MOG-IgG-associated diseases.

Mader, Simone / Kümpfel, Tania / Meinl, Edgar

Current opinion in neurology

2020 Volume 33, Issue 3, Page(s) 362–371

Abstract: Purpose of review: This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies.: Recent findings: Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a ... ...

Abstract	Purpose of review: This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies. Recent findings: Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune diseases of the central nervous system (CNS). Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to differences in clinical response of anti-CD20 therapy remains to be analyzed. Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19 + B cells), and satralizumab (anti-IL-6R blocking IL-6 actions). Summary: New insights into pathological mechanisms and therapeutic responses argue to consider NMOSD with AQP4-IgG and MOGAD as separate disease entities.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Aquaporin 4/immunology ; Autoantibodies/immunology ; Humans ; Immunoglobulin G/immunology ; Immunologic Factors/therapeutic use ; Myelin-Oligodendrocyte Glycoprotein/immunology ; Neuromyelitis Optica/drug therapy ; Neuromyelitis Optica/immunology
Chemical Substances	Antibodies, Monoclonal, Humanized ; Aquaporin 4 ; Autoantibodies ; Immunoglobulin G ; Immunologic Factors ; Myelin-Oligodendrocyte Glycoprotein ; inebilizumab (74T7185BMM) ; eculizumab (A3ULP0F556) ; satralizumab (YB18NF020M)
Language	English
Publishing date	2020-05-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000000813
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Article ; Online: Intramuscular vaccination against SARS-CoV-2 transiently induces neutralizing IgG rather than IgA in the saliva.

Winklmeier, Stephan / Rübsamen, Heike / Özdemir, Ceren / Wratil, Paul R / Lupoli, Gaia / Stern, Marcel / Schneider, Celine / Eisenhut, Katharina / Ho, Samantha / Wong, Hoi Kiu / Taskin, Damla / Petry, Marvin / Weigand, Michael / Eichhorn, Peter / Foesel, Bärbel U / Mader, Simone / Keppler, Oliver T / Kümpfel, Tania / Meinl, Edgar

Frontiers in immunology

2024 Volume 15, Page(s) 1330864

Abstract: The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of ... ...

Abstract	The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection.
MeSH term(s)	Humans ; BNT162 Vaccine ; Breakthrough Infections ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2 ; Saliva ; Vaccination ; Immunoglobulin A ; Immunoglobulin G
Chemical Substances	BNT162 Vaccine ; COVID-19 Vaccines ; Immunoglobulin A ; Immunoglobulin G
Language	English
Publishing date	2024-02-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1330864
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