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Book ; Online: Emerging Viruses: Host Immunity and Novel Therapeutic Interventions

Chen-Yu Hsu, Alan / Smed-Sörensen, Anna / Yuan Oh, Ding / Oshiumi, Hiroyuki

2019

Keywords	Medicine ; Immunology ; emerging viruses ; influenza viruses ; MERS-CoV ; Flavivirus ; Ebola virus ; Hantavirus
Size	1 electronic resource (226 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230296
ISBN	9782889457427 ; 2889457427
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Circulating Extracellular Vesicles Carry Immune Regulatory miRNAs and Regulate Vaccine Efficacy and Local Inflammatory Response After Vaccination.

Oshiumi, Hiroyuki

Frontiers in immunology

2021 Volume 12, Page(s) 685344

Abstract: Vaccination is the best prophylaxis for the prevention of infectious diseases, including coronavirus disease 2019. However, the efficacy of vaccines and onset of adverse reactions vary among individuals. Circulating extracellular vesicles (EVs) regulate ... ...

Abstract	Vaccination is the best prophylaxis for the prevention of infectious diseases, including coronavirus disease 2019. However, the efficacy of vaccines and onset of adverse reactions vary among individuals. Circulating extracellular vesicles (EVs) regulate the immune responses after vaccination by delivering microRNAs (miRNAs) to myeloid and lymphoid cells. Among these, miR-192 levels in serum EVs increase with aging, in an IL-6-dependent manner, reducing excessive IL-6 expression in aged mice, creating a negative feedback loop. Excessive IL-6 expression reduces vaccination efficacy in aged mice, while EV miR-192 improves efficacy in these aged mice as well, making this miRNA an interesting focus of study. miR-21 levels in serum EVs also increase with aging, and regulates the expression of IL-12 required for Th1 responses; therefore, EV miR-21 is expected to regulate vaccine efficacy. miR-451a, another important miRNA, is abundant in serum EVs and controls the expression of cytokines, such as type I interferon and IL-6. However, levels differ among individuals and correlate with local inflammatory symptoms experienced after a seasonal flu vaccination. These findings suggest the importance of EV miRNAs as a tool to improve vaccine efficacy and also as biomarkers to predict the immune response and adverse reactions after vaccinations.
MeSH term(s)	Aging/blood ; Aging/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Extracellular Vesicles/metabolism ; Humans ; Interferon Type I/biosynthesis ; Interferon Type I/immunology ; Interleukin-12 Subunit p35/biosynthesis ; Interleukin-12 Subunit p35/immunology ; Interleukin-6/biosynthesis ; Interleukin-6/immunology ; MicroRNAs/blood ; MicroRNAs/genetics ; SARS-CoV-2/immunology ; Th1 Cells/immunology ; Vaccination
Chemical Substances	COVID-19 Vaccines ; IL12A protein, human ; IL6 protein, human ; Interferon Type I ; Interleukin-12 Subunit p35 ; Interleukin-6 ; MIRN192 microRNA, human ; MIRN21 microRNA, human ; MIRN451 microRNA, human ; MicroRNAs
Language	English
Publishing date	2021-06-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.685344
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Recent Advances and Contradictions in the Study of the Individual Roles of Ubiquitin Ligases That Regulate RIG-I-Like Receptor-Mediated Antiviral Innate Immune Responses.

Oshiumi, Hiroyuki

Frontiers in immunology

2020 Volume 11, Page(s) 1296

Abstract: RIG-I and MDA5 are cytoplasmic viral RNA sensors and are essential for antiviral innate immune responses, such as type I interferon production. Post-translational modification is critical for the activation and inactivation of RIG-I and MDA5. At least ... ...

Abstract	RIG-I and MDA5 are cytoplasmic viral RNA sensors and are essential for antiviral innate immune responses, such as type I interferon production. Post-translational modification is critical for the activation and inactivation of RIG-I and MDA5. At least seven ubiquitin ligases have been reported to be involved in either K63- or K48-linked polyubiquitination of RIG-I and MDA5, and these ubiquitin ligases are further regulated by other factors. TRIM25 is an E3 ubiquitin ligase that delivers a K63-linked polyubiquitin moiety to the caspase activation and recruitment domains (CARDs) of RIG-I, thereby activating the antiviral innate immune response. Recent studies have shown that NDR2, ZCCHC3, and Lnczc3h7a promote TRIM25-mediated RIG-I activation. Riplet is another ubiquitin ligase that mediates the K63-linked polyubiquitination of the C-terminal domain (CTD) of RIG-I; however, it was also reported that Riplet delivers the K63-linked polyubiquitin moiety to the CARDs of RIG-I as well as to the CTD, thereby activating RIG-I. Further, there are several factors that attenuate the activation of RIG-I and MDA5. RNF125, TRIM40, and c-Cbl mediate K48-linked polyubiquitination and induce degradation of RIG-I and/or MDA5. USP21 and CYLD remove the K63-linked polyubiquitin chain from RIG-I, and NLRP12 inhibits polyubiquitin-mediated RIG-I activation. Although these new regulators have been reported, their distinctive roles and functional differences remain elusive, and in some cases, studies on the topic are contradictory to each other. In the present review, recent studies related to post-translational modifications of RIG-I and MDA5 are summarized, and several controversies and unanswered questions in this field are discussed.
MeSH term(s)	Animals ; DEAD Box Protein 58/metabolism ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Protein Binding ; Protein Processing, Post-Translational ; Receptors, Immunologic/metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Viral Proteins/metabolism ; Virus Diseases/immunology ; Virus Diseases/metabolism ; Virus Diseases/virology
Chemical Substances	Receptors, Immunologic ; Viral Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; RIGI protein, human (EC 3.6.1.-) ; DEAD Box Protein 58 (EC 3.6.4.13)
Language	English
Publishing date	2020-06-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01296
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [The innate immune response to SARS-CoV-2].

Takashima, Ken / Oshiumi, Hiroyuki

Uirusu

2021 Volume 71, Issue 1, Page(s) 33–40

MeSH term(s)	COVID-19 ; Humans ; Immune Evasion ; Immunity, Innate ; SARS-CoV-2
Language	Japanese
Publishing date	2021-12-08
Publishing country	Japan
Document type	Journal Article
ZDB-ID	603272-2
ISSN	0042-6857
ISSN	0042-6857
DOI	10.2222/jsv.71.33
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Article ; Online: E3 Ubiquitin Ligase Riplet Is Expressed in T Cells and Suppresses T Cell-Mediated Antitumor Immune Responses.

Iwamoto, Asuka / Tsukamoto, Hirotake / Nakayama, Hideki / Oshiumi, Hiroyuki

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 208, Issue 8, Page(s) 2067–2076

Abstract: The E3 ubiquitin ligase Riplet mediates retinoic acid-inducible gene-I polyubiquitination and is essential for viral-induced expression of type I IFNs in dendritic cells and macrophages. The function of Riplet in innate immunity has been well ... ...

Abstract	The E3 ubiquitin ligase Riplet mediates retinoic acid-inducible gene-I polyubiquitination and is essential for viral-induced expression of type I IFNs in dendritic cells and macrophages. The function of Riplet in innate immunity has been well demonstrated; however, its role in adaptive immunity during the antitumor immune response is unclear. In this study, we examined the role of Riplet in the T cell-mediated antitumor immune response. Riplet was expressed in T cells and upregulated in CD8
MeSH term(s)	Adaptive Immunity/immunology ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells ; Immunity, Innate/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Th1 Cells/immunology ; Ubiquitin-Protein Ligases/biosynthesis ; Ubiquitin-Protein Ligases/immunology
Chemical Substances	Rnf135 protein, mouse (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100096
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Zs.MG 28: Show issues

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Article ; Online: K63-linked polyubiquitination of LGP2 by Riplet regulates RIG-I-dependent innate immune response.

Kouwaki, Takahisa / Nishimura, Tasuku / Wang, Guanming / Nakagawa, Reiko / Oshiumi, Hiroyuki

EMBO reports

2022 Volume 24, Issue 2, Page(s) e54844

Abstract: Type I interferons (IFNs) exhibit strong antiviral activity and induce the expression of antiviral proteins. Since excessive expression of type I IFNs is harmful to the host, their expression should be turned off at the appropriate time. In this study, ... ...

Abstract	Type I interferons (IFNs) exhibit strong antiviral activity and induce the expression of antiviral proteins. Since excessive expression of type I IFNs is harmful to the host, their expression should be turned off at the appropriate time. In this study, we find that post-translational modification of LGP2, a member of the RIG-I-like receptor family, modulates antiviral innate immune responses. The LGP2 protein undergoes K63-linked polyubiquitination in response to cytoplasmic double-stranded RNAs or viral infection. Our mass spectrometry analysis reveals the K residues ubiquitinated by the Riplet ubiquitin ligase. LGP2 ubiquitination occurs with a delay compared to RIG-I ubiquitination. Interestingly, ubiquitination-defective LGP2 mutations increase the expression of type I IFN at a late phase, whereas the mutant proteins attenuate other antiviral proteins, such as SP100, PML, and ANKRD1. Our data indicate that delayed polyubiquitination of LGP2 fine-tunes RIG-I-dependent antiviral innate immune responses at a late phase of viral infection.
MeSH term(s)	Humans ; Antiviral Agents ; DEAD Box Protein 58/genetics ; DEAD Box Protein 58/metabolism ; DEAD-box RNA Helicases/genetics ; Immunity, Innate ; Interferon Type I/genetics ; Ubiquitin/metabolism ; Ubiquitination ; Virus Diseases
Chemical Substances	Antiviral Agents ; DEAD Box Protein 58 (EC 3.6.4.13) ; DEAD-box RNA Helicases (EC 3.6.4.13) ; Interferon Type I ; Ubiquitin ; RIGI protein, human (EC 3.6.1.-) ; DHX58 protein, human (EC 2.7.7.-)
Language	English
Publishing date	2022-12-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202254844
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 41: Show issues

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Article ; Online: The role of macrophages in anti-tumor immune responses: pathological significance and potential as therapeutic targets.

Tsukamoto, Hirotake / Komohara, Yoshihiro / Oshiumi, Hiroyuki

Human cell

2021 Volume 34, Issue 4, Page(s) 1031–1039

Abstract: Malignant tumors comprise various types of normal cells and tumor cells, and are infiltrated by large numbers of immune cells, including macrophages. The results of numerous studies on the function and significance of intratumoral macrophages (tumor- ... ...

Abstract	Malignant tumors comprise various types of normal cells and tumor cells, and are infiltrated by large numbers of immune cells, including macrophages. The results of numerous studies on the function and significance of intratumoral macrophages (tumor-associated macrophages) suggest that these macrophages generally enhance tumor progression rather than act as anti-tumor immune agents. Although much remains unknown, in this review, we attempt to describe the role of macrophages in the tumor microenvironment, and discuss their potential mechanisms on the recent immunotherapy.
MeSH term(s)	Cell Differentiation ; Disease Progression ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Macrophage Activation ; Macrophages/classification ; Macrophages/immunology ; Molecular Targeted Therapy ; Neoplasms/immunology ; Neoplasms/therapy ; Tumor Microenvironment/immunology
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-04-27
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1149134-6
ISSN	1749-0774 ; 0914-7470
ISSN (online)	1749-0774
ISSN	0914-7470
DOI	10.1007/s13577-021-00514-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: RIG-I-Like Receptor-Mediated Recognition of Viral Genomic RNA of Severe Acute Respiratory Syndrome Coronavirus-2 and Viral Escape From the Host Innate Immune Responses.

Kouwaki, Takahisa / Nishimura, Tasuku / Wang, Guanming / Oshiumi, Hiroyuki

Frontiers in immunology

2021 Volume 12, Page(s) 700926

Abstract: RIG-I-like receptors (RLR), RIG-I and MDA5, are cytoplasmic viral RNA sensors that recognize viral double-stranded RNAs and trigger signals to induce antiviral responses, including type I interferon production. Severe acute respiratory syndrome ... ...

Abstract	RIG-I-like receptors (RLR), RIG-I and MDA5, are cytoplasmic viral RNA sensors that recognize viral double-stranded RNAs and trigger signals to induce antiviral responses, including type I interferon production. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the coronavirus disease 2019 pandemic. However, the RLR role in innate immune response to SARS-CoV-2 has not been fully elucidated. Here, we studied the roles of RLR in cytokine expression responding to SARS-CoV-2 and found that not only MDA5 but also RIG-I are involved in innate immune responses in some types of human cells. Transfection of total RNAs extracted from SARS-CoV-2-infected cells into epithelial cells induced IFN-β, IP-10, and Ccl5 mRNA expression. The cytokine expression was reduced by knockout of either RIG-I or MDA5, suggesting that both proteins are required for appropriate innate immune response to SARS-CoV-2. Two viral genomic RNA regions strongly induced type I IFN expression, and a 200-base fragment of viral RNA preferentially induced type I IFN in a RIG-I-dependent manner. In contrast, SARS-CoV-2 infectious particles hardly induced cytokine expression, suggesting viral escape from the host response. Viral 9b protein inhibited RIG-I and MAVS interaction, and viral 7a protein destabilized the TBK1 protein, leading to attenuated IRF-3 phosphorylation required for type I IFN expression. Our data elucidated the mechanism underlying RLR-mediated response to SARS-CoV-2 infection and viral escape from the host innate immune response.
MeSH term(s)	COVID-19/immunology ; Gene Knockdown Techniques ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Immune Evasion ; Immunity, Innate ; Interferon Regulatory Factor-3/metabolism ; Interferon Type I/metabolism ; Interferon-Induced Helicase, IFIH1/genetics ; Interferon-Induced Helicase, IFIH1/metabolism ; Phosphorylation ; RNA, Viral/immunology ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism ; SARS-CoV-2/physiology ; Severe Acute Respiratory Syndrome/immunology ; Signal Transduction ; Viral Matrix Proteins/metabolism
Chemical Substances	IRF3 protein, human ; Interferon Regulatory Factor-3 ; Interferon Type I ; PLAAT4 protein, human ; RNA, Viral ; Receptors, Retinoic Acid ; Viral Matrix Proteins ; sars7a protein, SARS virus ; IFIH1 protein, human (EC 3.6.1.-) ; Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13)
Language	English
Publishing date	2021-06-25
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.2021.700926
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Article ; Online: Aging-Associated Extracellular Vesicles Contain Immune Regulatory microRNAs Alleviating Hyperinflammatory State and Immune Dysfunction in the Elderly.

Tsukamoto, Hirotake / Kouwaki, Takahisa / Oshiumi, Hiroyuki

iScience

2020 Volume 23, Issue 9, Page(s) 101520

Abstract: Aging-associated changes in the immune system often lead to immune dysfunction; however, the mechanisms that underlie this phenomenon have yet to be fully elucidated. This study found that the microRNA-192 (miR-192) is an aging-associated immune ... ...

Abstract	Aging-associated changes in the immune system often lead to immune dysfunction; however, the mechanisms that underlie this phenomenon have yet to be fully elucidated. This study found that the microRNA-192 (miR-192) is an aging-associated immune regulatory microRNA whose concentration was significantly increased in aged extracellular vesicles (EVs) due to the hyperinflammatory state of aged mice. Interestingly, EV miR-192 exhibited anti-inflammatory effects on macrophages. In our aged mouse model, aging was associated with prolonged inflammation in the lung upon stimulation with inactivated influenza whole virus particles (WVP), whereas EV miR-192 alleviated the prolonged inflammation associated with aging. The hyperinflammatory state of aged mice resulted in reduced production of specific antibodies and efficacy of vaccination with WVP; however, EV miR-192 attenuated this hyperinflammatory state and improved vaccination efficacy in aged mice. Our data indicate that aged EVs constitute a negative feedback loop that alleviates aging-associated immune dysfunction.
Language	English
Publishing date	2020-09-01
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101520
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Article ; Online: HPV vaccines induce trained immunity and modulate pro-inflammatory cytokine expression in response to secondary Toll-like receptor stimulations.

Yamaguchi, Mako / Mtali, Yohana S / Sonokawa, Hitomi / Takashima, Ken / Fukushima, Yoshimi / Kouwaki, Takahisa / Oshiumi, Hiroyuki

Microbiology and immunology

2023 Volume 68, Issue 2, Page(s) 65–74

Abstract: Cervical cancer is caused mostly by human papillomavirus (HPV), and several HPV vaccines have been developed to prevent its onset. Vaccines include antigens as well as adjuvants, with adjuvants playing an important role in activating the innate immune ... ...

Abstract	Cervical cancer is caused mostly by human papillomavirus (HPV), and several HPV vaccines have been developed to prevent its onset. Vaccines include antigens as well as adjuvants, with adjuvants playing an important role in activating the innate immune responses necessary for inducing adaptive immunological responses. Recent research has shown the presence of trained immunity inside the innate immune system. However, trained immunity conferred by HPV vaccinations is not well understood. In this work, we explored the innate immune responses and trained immunity caused by two HPV vaccines, Cervarix and Gardasil. Cervarix includes monophosphoryl lipid A and an aluminum adjuvant, and it significantly increased the expression of IL-6 and IFN-β mRNAs in RAW264.7 cells. On the contrary, Gardasil, which only includes an aluminum adjuvant, exhibited little cytokine expression but increased the expression of TLRs. Furthermore, Cervarix significantly increased IL-1β secretion from mouse macrophages, while Gardasil only mildly induced IL-1β secretion. Interestingly, initial stimulation with Gardasil enhanced the expression of IL-6 and TNF-α mRNAs upon secondary stimulation with TLR ligands, indicating that Gardasil induced trained immunity in macrophages. Moreover, Gardasil injection into mice resulted in enhanced TNF-α production in sera following secondary TLR stimulation. Our findings suggest that HPV vaccinations have the ability to induce trained immunity that modulate TLR ligand responses.
MeSH term(s)	Humans ; Animals ; Mice ; Cytokines ; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 ; Tumor Necrosis Factor-alpha ; Interleukin-6/genetics ; Trained Immunity ; Papillomavirus Infections/prevention & control ; Aluminum ; Papillomavirus Vaccines/genetics ; Adjuvants, Immunologic ; Toll-Like Receptors
Chemical Substances	Cytokines ; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Aluminum (CPD4NFA903) ; Papillomavirus Vaccines ; Adjuvants, Immunologic ; Toll-Like Receptors
Language	English
Publishing date	2023-12-17
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.13108
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