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Article ; Online: Pausing drugs and spacing vaccines: an open question - Authors' reply.

Rubbert-Roth, Andrea / Schmiedeberg, Kristin / von Kempis, Johannes

The Lancet. Rheumatology

2021 Volume 3, Issue 10, Page(s) e683–e684

Language	English
Publishing date	2021-09-22
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(21)00276-9
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Article ; Online: Anti-interleukin-23-directed therapy and the recurrence of severe allergic asthma.

Schmiedeberg, Kristin / Rassouli, Frank / von Kempis, Johannes / Rubbert-Roth, Andrea

Rheumatology (Oxford, England)

2022 Volume 61, Issue 8, Page(s) e219–e220

MeSH term(s)	Asthma/drug therapy ; Humans ; Hypersensitivity ; Immunoglobulin E ; Interleukin-23
Chemical Substances	Interleukin-23 ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2022-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac071
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article ; Online: Anti-SARS-CoV-2 mRNA vaccine in patients with rheumatoid arthritis.

Rubbert-Roth, Andrea / Vuilleumier, Nicolas / Ludewig, Burkhard / Schmiedeberg, Kristin / Haller, Christoph / von Kempis, Johannes

The Lancet. Rheumatology

2021 Volume 3, Issue 7, Page(s) e470–e472

Language	English
Publishing date	2021-06-08
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(21)00186-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Anti-SARS-CoV-2 mRNA vaccines as inducers of humoral response against apolipoprotein A-1?

Vuilleumier, Nicolas / Pagano, Sabrina / Ludewig, Burkhard / Schmiedeberg, Kristin / Haller, Christoph / von Kempis, Johannes / Rubbert-Roth, Andrea

European journal of clinical investigation

2021 Volume 52, Issue 2, Page(s) e13713

Abstract: Background: COVID-19 and some anti-SARS-CoV-2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients' prognosis in predisposed individuals. Autoantibodies directed against ... ...

Abstract	Background: COVID-19 and some anti-SARS-CoV-2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients' prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A-1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID-19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti-SARS-CoV-2 mRNA-based vaccination on AAA1 autoimmune biomarkers in RA patients. Methods: 20 healthy controls and 77 RA mRNA-based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS-CoV-2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded. Results: mRNA-based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol. Conclusions: mRNA-based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies.
MeSH term(s)	2019-nCoV Vaccine mRNA-1273/adverse effects ; 2019-nCoV Vaccine mRNA-1273/therapeutic use ; Adult ; Aged ; Apolipoprotein A-I/immunology ; Arthritis, Rheumatoid/immunology ; Autoantibodies/immunology ; BNT162 Vaccine/adverse effects ; BNT162 Vaccine/therapeutic use ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; COVID-19 Vaccines/therapeutic use ; Case-Control Studies ; Female ; Humans ; Immunity, Humoral/immunology ; Immunocompetence ; Immunoglobulin G ; Male ; Middle Aged ; SARS-CoV-2 ; mRNA Vaccines/adverse effects ; mRNA Vaccines/therapeutic use
Chemical Substances	Apolipoprotein A-I ; Autoantibodies ; COVID-19 Vaccines ; Immunoglobulin G ; mRNA Vaccines ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.13713
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Zs.A 677: Show issues

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Article ; Online: Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses.

Schmiedeberg, Kristin / Vuilleumier, Nicolas / Pagano, Sabrina / Albrich, Werner C / Ludewig, Burkhard / Kempis, Johannes von / Rubbert-Roth, Andrea

The Lancet. Rheumatology

2021 Volume 4, Issue 1, Page(s) e11–e13

Language	English
Publishing date	2021-10-26
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(21)00328-3
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Article ; Online: Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA.

Schmiedeberg, Kristin / Abela, Irene A / Pikor, Natalia Barbara / Vuilleumier, Nicolas / Schwarzmueller, Magdalena / Epp, Selina / Pagano, Sabrina / Grabherr, Sarah / Patterson, Angelica Brooke / Nussberger, Madalina / Trkola, Alexandra / Ludewig, Burkhard / von Kempis, Johannes / Rubbert-Roth, Andrea

RMD open

2022 Volume 8, Issue 2

Abstract: Objectives: To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity.: Methods: The RECOVER study was a ... ...

Abstract	Objectives: To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. Methods: The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. Results: In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. Conclusion: In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen.
MeSH term(s)	Humans ; SARS-CoV-2 ; Immunoglobulin A ; Prospective Studies ; COVID-19/prevention & control ; Arthritis, Rheumatoid ; Immunoglobulin G ; Immunoglobulin M ; Antiviral Agents ; Viral Proteins ; RNA, Messenger
Chemical Substances	Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Antiviral Agents ; Viral Proteins ; RNA, Messenger
Language	English
Publishing date	2022-10-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2022-002575
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Book ; Thesis: Molekulare Klonierung, Charakterisierung und Struktur-Funktions-Beziehungen von olfaktorischen Rezeptoren für Schlüsselaromastoffe

Schmiedeberg, Kristin

2004

Author's details	vorgelegt von Kristin Schmiedeberg
Language	German
Size	120 Bl, graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Potsdam, 2005
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: T Cells of Infants Are Mature, but Hyporeactive Due to Limited Ca2+ Influx.

Schmiedeberg, Kristin / Krause, Hardy / Röhl, Friedrich-Wilhelm / Hartig, Roland / Jorch, Gerhard / Brunner-Weinzierl, Monika C

PloS one

2016 Volume 11, Issue 11, Page(s) e0166633

Abstract: CD4 T cells in human infants and adults differ in the initiation and strength of their responses. The molecular basis for these differences is not yet understood. To address this the principle key molecular events of TCR- and CD28-induced signaling in ... ...

Abstract	CD4 T cells in human infants and adults differ in the initiation and strength of their responses. The molecular basis for these differences is not yet understood. To address this the principle key molecular events of TCR- and CD28-induced signaling in naive CD4 T cells, such as Ca2+ influx, NFAT expression, phosphorylation and translocation into the nucleus, ERK activation and IL-2 response, were analyzed over at least the first 3 years of life. We report dramatically reduced IL-2 and TNFα responses in naive CD31+ T cells during infancy. Looking at the obligatory Ca2+ influx required to induce T cell activation and proliferation, we demonstrate characteristic patterns of impairment for each stage of infancy that are partly due to the differential usage of Ca2+ stores. Consistent with those findings, translocation of NFATc2 is limited, but still dependent on Ca2+ influx as demonstrated by sensitivity to cyclosporin A (CsA) treatment. Thus weak Ca2+ influx functions as a catalyst for the implementation of restricted IL-2 response in T cells during infancy. Our studies also define limited mobilization of Ca2+ ions as a characteristic property of T cells during infancy. This work adds to our understanding of infants' poor T cell responsiveness against pathogens.
MeSH term(s)	Adolescent ; Adult ; CD28 Antigens/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Calcium/metabolism ; Cell Nucleus/metabolism ; Cells, Cultured ; Child ; Child, Preschool ; Cyclosporine/pharmacology ; Egtazic Acid/pharmacology ; Fetal Blood/cytology ; Humans ; Infant ; Infant, Newborn ; Interleukin-2/metabolism ; Lymphocyte Activation/drug effects ; Middle Aged ; NFATC Transcription Factors/metabolism ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Young Adult
Chemical Substances	CD28 Antigens ; Interleukin-2 ; NFATC Transcription Factors ; Platelet Endothelial Cell Adhesion Molecule-1 ; Tumor Necrosis Factor-alpha ; Egtazic Acid (526U7A2651) ; Cyclosporine (83HN0GTJ6D) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0166633
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Article: Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2.

Schmiedeberg, Kristin / Shirokova, Elena / Weber, Hans-Peter / Schilling, Boris / Meyerhof, Wolfgang / Krautwurst, Dietmar

Journal of structural biology

2007 Volume 159, Issue 3, Page(s) 400–412

Abstract: An interaction of odorants with olfactory receptors is thought to be the initial step in odorant detection. However, ligands have been reported for only 6 out of 380 human olfactory receptors, with their structural determinants of odorant recognition ... ...

Abstract	An interaction of odorants with olfactory receptors is thought to be the initial step in odorant detection. However, ligands have been reported for only 6 out of 380 human olfactory receptors, with their structural determinants of odorant recognition just beginning to emerge. Guided by the notion that amino acid positions that interact with specific odorants would be conserved in orthologs, but variable in paralogs, and based on the prediction of a set of 22 of such amino acid positions, we have combined site-directed mutagenesis, rhodopsin-based homology modelling, and functional expression in HeLa/Olf cells of receptors OR1A1 and OR1A2. We found that (i) their odorant profiles are centred around citronellic terpenoid structures, (ii) two evolutionary conserved amino acid residues in transmembrane domain 3 are necessary for the responsiveness of OR1A1 and the mouse ortholog Olfr43 to (S)-(-)-citronellol, (iii) changes at these two positions are sufficient to account for the differential (S)-(-)-citronellol responsiveness of the paralogs OR1A1 and OR1A2, and (iv) the interaction sites for (S)-(-)-citronellal and (S)-(-)-citronellol differ in both human receptors. Our results show that the orientation of odorants within a homology modelling-derived binding pocket of olfactory receptor orthologs is defined by evolutionary conserved amino acid positions.
MeSH term(s)	Aldehydes/chemistry ; Amino Acid Sequence ; Animals ; Conserved Sequence ; HeLa Cells ; Humans ; Ligands ; Mice ; Molecular Sequence Data ; Monoterpenes/chemistry ; Mutagenesis, Site-Directed ; Odorants ; Receptors, Odorant/chemistry ; Receptors, Odorant/genetics ; Rhodopsin/chemistry ; Rhodopsin/genetics ; Sequence Analysis, Protein ; Smell/genetics
Chemical Substances	Aldehydes ; Ligands ; Monoterpenes ; OR1A1 protein, human ; OR1A2 protein, human ; Receptors, Odorant ; Rhodopsin (9009-81-8) ; citronellol (P01OUT964K) ; citronellal (QB99VZZ7GZ)
Language	English
Publishing date	2007-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1032718-6
ISSN	1095-8657 ; 1047-8477
ISSN (online)	1095-8657
ISSN	1047-8477
DOI	10.1016/j.jsb.2007.04.013
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Zs.A 1428: Show issues

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Article: Identification of specific ligands for orphan olfactory receptors. G protein-dependent agonism and antagonism of odorants.

Shirokova, Elena / Schmiedeberg, Kristin / Bedner, Peter / Niessen, Heiner / Willecke, Klaus / Raguse, Jan-Dirk / Meyerhof, Wolfgang / Krautwurst, Dietmar

The Journal of biological chemistry

2004 Volume 280, Issue 12, Page(s) 11807–11815

Abstract: Olfactory receptors are the largest group of orphan G protein-coupled receptors with an infinitely small number of agonists identified out of thousands of odorants. The de-orphaning of olfactory receptor (OR) is complicated by its combinatorial odorant ... ...

Abstract	Olfactory receptors are the largest group of orphan G protein-coupled receptors with an infinitely small number of agonists identified out of thousands of odorants. The de-orphaning of olfactory receptor (OR) is complicated by its combinatorial odorant coding and thus requires large scale odorant and receptor screening and establishing receptor-specific odorant profiles. Here, we report on the stable reconstitution of OR-specific signaling in HeLa/Olf cells via G protein alphaolf and adenylyl cyclase type-III to the Ca2+ influx-mediating olfactory cyclic nucleotide-gated CNGA2 channel. We demonstrate the central role of Galphaolf in odorant-specific signaling out of OR. The employment of the non-typical G protein alpha15 dramatically altered the odorant specificities of 3 of 7 receptors that had been characterized previously by different groups. We further show for two OR that an odorant may be an agonist or antagonist, depending on the G protein used. HeLa/Olf cells proved suitable for high-throughput screening in fluorescence-imaging plate reader experiments, resulting in the de-orphaning of two new OR for the odorant (-)citronellal from an expression library of 93 receptors. To demonstrate the G protein dependence of its odorant response pattern, we screened the most sensitive (-)citronellal receptor Olfr43 versus 94 odorants simultaneously in the presence of Galpha15 or Galphaolf. We finally established an EC50-ranking odorant profile for Olfr43 in HeLa/Olf cells. In summary, we conclude that, in heterologous systems, odorants may function as agonists or antagonists, depending on the G protein used. HeLa/Olf cells provide an olfactory model system for functional expression and de-orphaning of OR.
MeSH term(s)	Acyclic Monoterpenes ; Aldehydes/pharmacology ; Calcium/metabolism ; Cyclic AMP/biosynthesis ; GTP-Binding Proteins/physiology ; HeLa Cells ; Humans ; Isoproterenol/pharmacology ; Ligands ; Monoterpenes/pharmacology ; Receptors, Odorant/agonists ; Receptors, Odorant/antagonists & inhibitors ; Receptors, Odorant/metabolism
Chemical Substances	Acyclic Monoterpenes ; Aldehydes ; Ligands ; Monoterpenes ; Receptors, Odorant ; Cyclic AMP (E0399OZS9N) ; GTP-Binding Proteins (EC 3.6.1.-) ; Isoproterenol (L628TT009W) ; citronellal (QB99VZZ7GZ) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2004-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M411508200
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