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Article ; Online: Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With

Sender, Vicky / Hentrich, Karina / Henriques-Normark, Birgitta

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 643326

Abstract: Secondary bacterial infections enhance the disease burden of influenza infections substantially. ...

Abstract	Secondary bacterial infections enhance the disease burden of influenza infections substantially.
MeSH term(s)	COVID-19/complications ; Coinfection ; Host-Pathogen Interactions/immunology ; Humans ; Influenza, Human/complications ; Pneumococcal Infections/pathology ; Respiratory System/pathology ; Respiratory Tract Infections/microbiology ; Respiratory Tract Infections/virology ; Streptococcus pneumoniae
Language	English
Publishing date	2021-03-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.643326
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Proton Motive Force Disruptors Block Bacterial Competence and Horizontal Gene Transfer.

Domenech, Arnau / Brochado, Ana Rita / Sender, Vicky / Hentrich, Karina / Henriques-Normark, Birgitta / Typas, Athanasios / Veening, Jan-Willem

Cell host & microbe

2020 Volume 27, Issue 4, Page(s) 544–555.e3

Abstract: Streptococcus pneumoniae is a commensal of the human nasopharynx that can also cause severe antibiotic-resistant infections. Antibiotics drive the spread of resistance by inducing S. pneumoniae competence, in which bacteria express the transformation ... ...

Abstract	Streptococcus pneumoniae is a commensal of the human nasopharynx that can also cause severe antibiotic-resistant infections. Antibiotics drive the spread of resistance by inducing S. pneumoniae competence, in which bacteria express the transformation machinery that facilitates uptake of exogenous DNA and horizontal gene transfer (HGT). We performed a high-throughput screen and identified potent inhibitors of S. pneumoniae competence, called COM-blockers. COM-blockers limit competence by inhibiting the proton motive force (PMF), thereby disrupting export of a quorum-sensing peptide that regulates the transformation machinery. Known chemical PMF disruptors and alterations in pH homeostasis similarly inhibit competence. COM-blockers limit transformation of clinical multi-drug-resistant strains and HGT in infected mice. At their active concentrations, COM-blockers do not affect growth, compromise antibiotic activity, or elicit detectable resistance. COM-blockers provide an experimental tool to inhibit competence and other PMF-involved processes and could help reduce the spread of virulence factors and antibiotic resistance in bacteria. VIDEO ABSTRACT.
MeSH term(s)	Animals ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/drug effects ; Drug Resistance, Microbial/drug effects ; Drug Resistance, Multiple/drug effects ; Gene Transfer, Horizontal/drug effects ; Humans ; Mice ; Proton-Motive Force ; Quorum Sensing/drug effects ; Streptococcus pneumoniae/drug effects ; Streptococcus pneumoniae/metabolism ; Virulence Factors
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; Virulence Factors ; competence factor, Streptococcus
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2020.02.002
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Article ; Online: Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR.

Hentrich, Karina / Löfling, Jonas / Pathak, Anuj / Nizet, Victor / Varki, Ajit / Henriques-Normark, Birgitta

Cell host & microbe

2016 Volume 20, Issue 3, Page(s) 307–317

Abstract: Streptococcus pneumoniae is a human-adapted pathogen that encounters terminally sialylated glycoconjugates and free sialic acid (Sia) in the airways. Upon scavenging by the bacterial sialidase NanA, Sias serve as carbon sources for the bacteria. Unlike ... ...

Abstract	Streptococcus pneumoniae is a human-adapted pathogen that encounters terminally sialylated glycoconjugates and free sialic acid (Sia) in the airways. Upon scavenging by the bacterial sialidase NanA, Sias serve as carbon sources for the bacteria. Unlike most animals in which cytidine-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts Sia N-acetylneuraminic acid (Neu5Ac) into N-glycolylneuraminic acid (Neu5Gc), humans have an inactive CMAH, causing an absence of Neu5Gc and excess Neu5Ac. We find that pneumococcal challenge in Cmah(-/-) mice leads to heightened bacterial loads, virulence, and NanA expression. In vitro, NanA is upregulated in response to Neu5Ac compared with Neu5Gc, a process controlled by the two-component response regulator CiaR and requiring Sia uptake by the transporter SatABC. Additionally, compared with Neu5Gc, Neu5Ac increases pneumococcal resistance to antimicrobial reactive oxygen species in a CiaR-dependent manner. Thus, S. pneumoniae senses and responds to Neu5Ac, leading to CiaR activation and increased virulence and potentially explaining the greater susceptibility in humans.
MeSH term(s)	Animals ; Bacterial Load ; Bacterial Proteins/metabolism ; Disease Models, Animal ; Gene Expression Regulation, Bacterial ; Mice ; Mice, Knockout ; Mixed Function Oxygenases/deficiency ; N-Acetylneuraminic Acid/metabolism ; Pneumonia, Pneumococcal/microbiology ; Protein Kinases/metabolism ; Streptococcus pneumoniae/drug effects ; Streptococcus pneumoniae/physiology ; Virulence Factors/biosynthesis
Chemical Substances	Bacterial Proteins ; Virulence Factors ; Mixed Function Oxygenases (EC 1.-) ; CMPacetylneuraminate monooxygenase (EC 1.14.18.2) ; Protein Kinases (EC 2.7.-) ; CiaR protein, Streptococcus pneumoniae (EC 2.7.3.-) ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2016-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2016.07.019
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Article ; Online: Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.

Sender, Vicky / Hentrich, Karina / Pathak, Anuj / Tan Qian Ler, Alicia / Embaie, Bethel Tesfai / Lundström, Susanna L / Gaetani, Massimiliano / Bergstrand, Jan / Nakamoto, Rei / Sham, Lok-To / Widengren, Jerker / Normark, Staffan / Henriques-Normark, Birgitta

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 49, Page(s) 31386–31397

Abstract: Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar ... ...

Abstract	Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Bacterial Proteins/metabolism ; Capillaries/pathology ; Glucose/metabolism ; Humans ; Inflammation/complications ; Inflammation/pathology ; Influenza, Human/microbiology ; Mice, Inbred C57BL ; Models, Biological ; Molecular Chaperones/metabolism ; Orthomyxoviridae Infections/microbiology ; Oxidation-Reduction ; Oxidative Stress ; Phagocytosis ; Pneumococcal Infections/microbiology ; Respiratory System/microbiology ; Respiratory System/pathology ; Respiratory System/virology ; Streptococcus pneumoniae/growth & development
Chemical Substances	Antioxidants ; Bacterial Proteins ; Molecular Chaperones ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2012265117
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Toll-Like Receptor 3/TRIF-Dependent IL-12p70 Secretion Mediated by Streptococcus pneumoniae RNA and Its Priming by Influenza A Virus Coinfection in Human Dendritic Cells.

Spelmink, Laura / Sender, Vicky / Hentrich, Karina / Kuri, Thomas / Plant, Laura / Henriques-Normark, Birgitta

mBio

2016 Volume 7, Issue 2, Page(s) e00168–16

Abstract: Unlabelled: A functional immune response is crucial to prevent and limit infections with Streptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types ...

Abstract	Unlabelled: A functional immune response is crucial to prevent and limit infections with Streptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types via antigen presentation and secretion of cytokines. In this study, we set out to understand how pneumococci activate human monocyte-derived DCs to produce interleukin-12 (IL-12) p70, an important cytokine during pneumococcal infections. We show that IL-12p70 production requires uptake of bacteria as well as the presence of the adaptor molecule TRIF, which is known to transfer signals of Toll-like receptor 3 (TLR3) or TLR4 from the endosome into the cell. While TLR4 is redundant for IL-12p70 production in DCs, we found that TLR3 is required to induce full IL-12p70 secretion. Influenza A virus (IAV) infection of DCs did not induce IL-12p70 but markedly upregulated TLR3 expression that during coinfection with S. pneumoniae significantly enhanced IL-12p70 secretion. Finally, we show that pneumococcal RNA can act as a bacterial stimulus for TLR3 and that it is a key signal to induce IL-12p70 production during challenge of DCs with pneumococci. Importance: Streptococcus pneumoniae, a common colonizer of the nose, is the causative agent of severe and deadly diseases. A well-orchestrated immune response is vital to prevent and limit these diseases. Dendritic cells (DCs) reside in the mucosal linings of the lungs and sample antigens. They are activated by pathogens to present antigens and secrete cytokines. While many studies focus on murine models, we focused our work on human monocyte-derived DCs. We found that pneumococcal RNA is an important stimulus in DCs to activate the endosomal receptor TLR3, a receptor previously not identified to sense pneumococci, and its adaptor molecule TRIF. This leads to secretion of the cytokine interleukin-12 (IL-12). Severe pneumococcal pneumonia occurs closely after influenza A virus (IAV) infection. We show that IAV infection upregulates TLR3 in DCs, which sensitizes the cells to endosomal pneumococcal RNA. This new insight contributes to unlock the interplay between pneumococci, IAV, and humans.
MeSH term(s)	Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/immunology ; Coinfection/immunology ; Coinfection/microbiology ; Coinfection/virology ; Cytokines/genetics ; Cytokines/immunology ; Dendritic Cells/immunology ; Dendritic Cells/microbiology ; Dendritic Cells/virology ; Humans ; Influenza A virus/immunology ; Influenza A virus/physiology ; Influenza, Human/genetics ; Influenza, Human/immunology ; Influenza, Human/virology ; Interleukin-12/genetics ; Interleukin-12/immunology ; Monocytes/immunology ; Pneumococcal Infections/genetics ; Pneumococcal Infections/immunology ; Pneumococcal Infections/microbiology ; RNA, Bacterial/genetics ; RNA, Bacterial/immunology ; Streptococcus pneumoniae/genetics ; Streptococcus pneumoniae/immunology ; Streptococcus pneumoniae/physiology ; Toll-Like Receptor 3/genetics ; Toll-Like Receptor 3/immunology
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Cytokines ; RNA, Bacterial ; TICAM1 protein, human ; TLR3 protein, human ; Toll-Like Receptor 3 ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2016-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00168-16
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Article ; Online: Toll-Like Receptor 3/TRIF-Dependent IL-12p70 Secretion Mediated by Streptococcus pneumoniae RNA and Its Priming by Influenza A Virus Coinfection in Human Dendritic Cells

Laura Spelmink / Vicky Sender / Karina Hentrich / Thomas Kuri / Laura Plant / Birgitta Henriques-Normark

mBio, Vol 7, Iss 2, p e00168-

2016 Volume 16

Abstract: A functional immune response is crucial to prevent and limit infections with Streptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types via antigen ... ...

Abstract	A functional immune response is crucial to prevent and limit infections with Streptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types via antigen presentation and secretion of cytokines. In this study, we set out to understand how pneumococci activate human monocyte-derived DCs to produce interleukin-12 (IL-12) p70, an important cytokine during pneumococcal infections. We show that IL-12p70 production requires uptake of bacteria as well as the presence of the adaptor molecule TRIF, which is known to transfer signals of Toll-like receptor 3 (TLR3) or TLR4 from the endosome into the cell. While TLR4 is redundant for IL-12p70 production in DCs, we found that TLR3 is required to induce full IL-12p70 secretion. Influenza A virus (IAV) infection of DCs did not induce IL-12p70 but markedly upregulated TLR3 expression that during coinfection with S. pneumoniae significantly enhanced IL-12p70 secretion. Finally, we show that pneumococcal RNA can act as a bacterial stimulus for TLR3 and that it is a key signal to induce IL-12p70 production during challenge of DCs with pneumococci.
Keywords	Science ; Q ; Microbiology ; QR1-502
Subject code	570
Language	English
Publishing date	2016-03-01T00:00:00Z
Publisher	American Society for Microbiology
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Sepsis bei neutropenischen Patienten

Kochanek, Matthias / Schalk, Enrico / Bergwelt, Michael von / Beutel, Karin / Buchheidt, Dieter / Hentrich, Marcus / Kiehl, Michael G. / Liebregts, Tobias / Lilienfeld-Toal, Marie von / Claßen, Annika / Mellinghoff, Sibylle Christiane / Penack, Olaf / Böll, Boris / Piepel, Christiane

Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen

(Onkopedia Leitlinien)

2019

Abstract: Sepsis und septischer Schock gehören zu den führenden Todesursachen bei Patienten* mit Chemotherapie-induzierter Neutropenie. Entscheidend sind Wahrnehmung der charakteristischen Symptome und rasches Handeln. Das optimale Management kann sich bei ... ...

Institution	Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie Schweizerische Gesellschaft für Medizinische Onkologie Schweizerische Gesellschaft für Hämatologie Deutsche Gesellschaft für Hämatologie und Onkologie / Arbeitsgemeinschaft Infektiologie Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin
Author's details	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V., OeGHO - Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie, SSMO/SSOM/SGMO - Schweizerische Gesellschaft für Medizinische Onkologie, SGH-SSH - Schweizerische Gesellschaft für Hämatologie/Société Suisse d'Hématologie ; Autoren: Matthias Kochanek, Enrico Schalk, Michael von Bergwelt-Baildon, Karin Beutel, Dieter Buchheidt, Marcus Hentrich, Michael Kiehl, Tobias Liebregts, Marie von Lilienfeld-Toal, Annika-Yanina Claßen, Sibylle Mellinghoff, Olaf Penack, Boris Böll, Christiane Piepel für die Arbeitsgemeinschaft Infektionen (AGIHO) der DGHO und die Arbeitsgruppe iCHOP von DGHO und DGIIN
Series title	Onkopedia Leitlinien
Abstract	Sepsis und septischer Schock gehören zu den führenden Todesursachen bei Patienten* mit Chemotherapie-induzierter Neutropenie. Entscheidend sind Wahrnehmung der charakteristischen Symptome und rasches Handeln. Das optimale Management kann sich bei neutropenen und nicht-neutropenen Patienten unterscheiden. Die Leitlinie ‚Management der Sepsis bei neutropenischen Patienten‘ wurde von der Arbeitsgemeinschaft Infektionen der DGHO (AGIHO) für die Diagnostik und Therapie dieser Patienten erstellt [1]. Grundlagen sind eine systematische Literaturrecherche, die einheitliche Bewertung der Evidenzstärke [2] und ein Konsensfindungsprozess. Dies ist die Kurzfassung dieser Empfehlungen.
Subject code	610
Language	German
Size	1 Online-Ressource (13 Seiten), Diagramme
Edition	Stand: April 2019
Publisher	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V
Publishing place	Berlin
Publishing country	Germany
Document type	Book ; Online
Note	Autoren früherer Versionen: Stefan Aebi, Maximilian Christopeit, Carolin Krämer, Helmut Ostermann, Olaf Penack, Mark Reinwald, Hans-Jürgen Salwender, Martin Schmidt-Hieber, Thomas Weber ; Open Access
HBZ-ID	HT020383297
DOI	10.4126/FRL01-006419185
Database	Repository for Life Sciences

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Book ; Online: Impfungen bei Tumorpatienten

Rieger, Christina / Liss, Blasius Janusch / Mellinghoff, Sibylle Christiane / Buchheidt, Dieter / Cornely, Oliver Andreas / Egerer, Gerlinde / Heinz, Werner / Hentrich, Marcus / Maschmeyer, Georg / Mayer, Karin Tina / Sandherr, Michael / Silling, Gerda / Ullmann, Andrew / Vehreschild, Maria J. G. T. / Lilienfeld-Toal, Marie von / Wolf, Hans-Heinrich / Giesen, Nicola

Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen

(Onkopedia Leitlinien)

2019

Abstract: Infektiöse Komplikationen sind eine wesentliche Ursache der Morbidität und Mortalität systemischer Tumortherapie. Prävention durch Impfungen ist ein wichtiger Aspekt der Patientenbetreuung. Dabei müssen immunsuppressive Einflüsse sowohl der ... ...

Institution	Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie Schweizerische Gesellschaft für Medizinische Onkologie Schweizerische Gesellschaft für Hämatologie
Author's details	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V., OeGHO - Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie, SSMO/SSOM/SGMO - Schweizerische Gesellschaft für Medizinische Onkologie, SGH-SSH - Schweizerische Gesellschaft für Hämatologie/Société Suisse d'Hématologie ; Autoren: Christina Rieger, Blasius Liss, Sibylle Mellinghoff, Dieter Buchheidt, Oliver A. Cornely, Gerlinde Egerer, Werner Heinz, Marcus Hentrich, Georg Maschmeyer, Karin Mayer, Michael Sandherr, Gerda Silling, Andrew J. Ullmann, Maria J. G. T. Vehreschild, Marie von Lilienfeld-Toal, Hans-Heinrich Wolf, Nicola Lehners für die Arbeitsgemeinschaft Infektionen (AGIHO) der DGHO
Series title	Onkopedia Leitlinien
Abstract	Infektiöse Komplikationen sind eine wesentliche Ursache der Morbidität und Mortalität systemischer Tumortherapie. Prävention durch Impfungen ist ein wichtiger Aspekt der Patientenbetreuung. Dabei müssen immunsuppressive Einflüsse sowohl der Grundkrankheit als auch der antineoplastischen Therapie berücksichtigt werden. Diese Empfehlungen schließen die Hochdosistherapie mit autologer Stammzelltransplantation ein, während die allogene Stammzelltransplantation Gegenstand einer eigenen Leitlinie ist. Die Leitlinie ‚Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors’ wurde von der Arbeitsgemeinschaft Infektionen der DGHO (AGIHO) für die Diagnostik und Therapie dieser Patienten erstellt [1]. Grundlagen der Empfehlungen sind eine systematische Literaturrecherche, die einheitliche Bewertung der Evidenzstärke [2] und ein Konsensfindungsprozess. Dies ist die Kurzfassung dieser Empfehlungen.
Subject code	610
Language	German
Size	1 Online-Ressource (9 Seiten)
Edition	Stand: April 2019
Publisher	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V
Publishing place	Berlin
Publishing country	Germany
Document type	Book ; Online
Note	Open Access
HBZ-ID	HT020614848
DOI	10.4126/FRL01-006423546
Database	Repository for Life Sciences

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Book ; Online: Impfungen bei Tumorpatienten

Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen

(Onkopedia Leitlinien)

2019

Institution	Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie Schweizerische Gesellschaft für Medizinische Onkologie Schweizerische Gesellschaft für Hämatologie Deutsche Gesellschaft für Hämatologie und Onkologie / Arbeitsgemeinschaft Infektiologie
Author's details	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V., OeGHO - Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie, SSMO/SSOM/SGMO - Schweizerische Gesellschaft für Medizinische Onkologie, SGH-SSH - Schweizerische Gesellschaft für Hämatologie/Société Suisse d'Hématologie ; Autoren: Christina Rieger, Blasius Liss, Sibylle Mellinghoff, Dieter Buchheidt, Oliver A. Cornely, Gerlinde Egerer, Werner Heinz, Marcus Hentrich, Georg Maschmeyer, Karin Mayer, Michael Sandherr, Gerda Silling, Andrew J. Ullmann, Maria J.G.T. Vehreschild, Marie von Lilienfeld-Toal, Hans-Heinrich Wolf, Nicola Lehners für die Arbeitsgemeinschaft Infektionen (AGIHO) der DGHO
Series title	Onkopedia Leitlinien
Abstract	Infektiöse Komplikationen sind eine wesentliche Ursache der Morbidität und Mortalität systemischer Tumortherapie. Prävention durch Impfungen ist ein wichtiger Aspekt der Patientenbetreuung. Dabei müssen immunsuppressive Einflüsse sowohl der Grundkrankheit als auch der antineoplastischen Therapie berücksichtigt werden. Diese Empfehlungen schließen die Hochdosistherapie mit autologer Stammzelltransplantation ein, während die allogene Stammzelltransplantation Gegenstand einer eigenen Leitlinie ist. Die Leitlinie ‚Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors’ wurde von der Arbeitsgemeinschaft Infektionen der DGHO (AGIHO) für die Diagnostik und Therapie dieser Patienten erstellt [1]. Grundlagen der Empfehlungen sind eine systematische Literaturrecherche, die einheitliche Bewertung der Evidenzstärke [2] und ein Konsensfindungsprozess. Dies ist die Kurzfassung dieser Empfehlungen.
Subject code	610
Language	German
Size	1 Online-Ressource (9 Seiten)
Edition	Stand: April 2019
Publisher	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V
Publishing place	Berlin
Publishing country	Germany
Document type	Book ; Online
Note	Open Access
HBZ-ID	HT020276141
DOI	10.4126/FRL01-006417384
Database	Repository for Life Sciences

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Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: LRRK2 guides the actin cytoskeleton at growth cones together with ARHGEF7 and Tropomyosin 4.

Häbig, Karina / Gellhaar, Sandra / Heim, Birgit / Djuric, Verena / Giesert, Florian / Wurst, Wolfgang / Walter, Carolin / Hentrich, Thomas / Riess, Olaf / Bonin, Michael

Biochimica et biophysica acta

2013 Volume 1832, Issue 12, Page(s) 2352–2367

Abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of Parkinson's disease (PD). However, LRRK2 function and molecular mechanisms causing the parkinsonian phenotype remain widely unknown. Most of LRRK2 ... ...

Abstract	Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of Parkinson's disease (PD). However, LRRK2 function and molecular mechanisms causing the parkinsonian phenotype remain widely unknown. Most of LRRK2 knockdown and overexpression models strengthen the relevance of LRRK2 in regulating neurite outgrowth. We have recently identified ARHGEF7 as the first guanine nucleotide exchange factor (GEF) of LRRK2. This GEF is influencing neurite outgrowth through regulation of actin polymerization. Here, we examined the expression profile of neuroblastoma cells with reduced LRRK2 and ARHGEF7 levels to identify additional partners of LRRK2 in this process. Tropomyosins (TPMs), and in particular TPM4, were the most interesting candidates next to other actin cytoskeleton regulating transcripts in this dataset. Subsequently, enhanced neurite branching was shown using primary hippocampal neurons of LRRK2 knockdown animals. Furthermore, we observed an enhanced number of growth cones per neuron and a mislocalization and dysregulation of ARHGEF7 and TPM4 in these neuronal compartments. Our results reveal a fascinating connection between the neurite outgrowth phenotype of LRRK2 models and the regulation of actin polymerization directing further investigations of LRRK2-related pathogenesis.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Animals ; Biomarkers/metabolism ; Blotting, Western ; Cell Proliferation ; Cells, Cultured ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Growth Cones/metabolism ; Guanine Nucleotide Exchange Factors ; Hippocampus/cytology ; Hippocampus/metabolism ; Humans ; Immunoenzyme Techniques ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Mice ; Mice, Knockout ; NIH 3T3 Cells ; Neurites/metabolism ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Neurons/cytology ; Neurons/metabolism ; Oligonucleotide Array Sequence Analysis ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Serine-Threonine Kinases/physiology ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Rho Guanine Nucleotide Exchange Factors/antagonists & inhibitors ; Rho Guanine Nucleotide Exchange Factors/genetics ; Rho Guanine Nucleotide Exchange Factors/metabolism ; Tropomyosin/genetics ; Tropomyosin/metabolism
Chemical Substances	ARHGEF7 protein, human ; Biomarkers ; Guanine Nucleotide Exchange Factors ; RNA, Messenger ; RNA, Small Interfering ; Rho Guanine Nucleotide Exchange Factors ; TPM4 protein, human ; Tropomyosin ; LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; Lrrk2 protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2013-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2013.09.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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