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Article ; Online: IL-1 receptor antagonist, MIS-C, and the peculiar autoimmunity of SARS-CoV-2.

Bassiri, Hamid / Canna, Scott W

The Lancet. Rheumatology

2022 Volume 4, Issue 5, Page(s) e305–e307

Language	English
Publishing date	2022-03-29
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(22)00090-X
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Species Differences in Blood Lymphocyte Responses After Spinal Cord Injury.

Ayala, Carlos / Fishman, Morgan / Noyelle, Margot / Bassiri, Hamid / Young, Wise

Journal of neurotrauma

2023 Volume 40, Issue 9-10, Page(s) 807–819

Abstract: People with spinal cord injury (SCI) get recurrent infections, such as urinary tract infections (UTIs) and pneumonias, that cause mortality and worsen neurological recovery. Over the past decades, researchers have proposed that post-SCI lymphopenia and ... ...

Abstract	People with spinal cord injury (SCI) get recurrent infections, such as urinary tract infections (UTIs) and pneumonias, that cause mortality and worsen neurological recovery. Over the past decades, researchers have proposed that post-SCI lymphopenia and decreased lymphocyte function increase susceptibility to infections and worsen neurological outcome in humans, leading to a condition called SCI-induced immune depression syndrome (SCI-IDS). In this review, we explore how SCI affects blood lymphocyte homeostasis and function in humans and rodents. Understanding how SCI affects blood lymphocytes will help the management of recurrent infections in spinal cord injured people and shed light on the clinical translation of findings in animal models to humans.
MeSH term(s)	Animals ; Humans ; Reinfection ; Species Specificity ; Spinal Cord Injuries ; Lymphocytes ; Spinal Cord
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2022.0122
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Distinct Bioenergetic Features of Human Invariant Natural Killer T Cells Enable Retained Functions in Nutrient-Deprived States.

Khurana, Priya / Burudpakdee, Chakkapong / Grupp, Stephan A / Beier, Ulf H / Barrett, David M / Bassiri, Hamid

Frontiers in immunology

2021 Volume 12, Page(s) 700374

Abstract: Invariant natural killer T (iNKT) cells comprise a unique subset of lymphocytes that are primed for activation and possess innate NK-like functional features. Currently, iNKT cell-based immunotherapies remain in early clinical stages, and little is known ...

Abstract	Invariant natural killer T (iNKT) cells comprise a unique subset of lymphocytes that are primed for activation and possess innate NK-like functional features. Currently, iNKT cell-based immunotherapies remain in early clinical stages, and little is known about the ability of these cells to survive and retain effector functions within the solid tumor microenvironment (TME) long-term. In conventional T cells (T
MeSH term(s)	Cells, Cultured ; Energy Metabolism/immunology ; Humans ; Lymphocyte Activation/immunology ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/metabolism
Language	English
Publishing date	2021-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2021.700374
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Article: Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation.

Vella, Laura A / Berna, Amalia Z / Blatz, Allison M / Logan, Joey / Sharma, Priya / Liu, Yang / Tedesco, Jonathan / Toland, Cara / Babiker, Leena / Hafertepe, Kathryn / Kammerman, Shane / Novacek, Josef / Akaho, Elikplim / Gonzalez, Alexander K / Taylor, Deanne / Diorio, Caroline / Balamuth, Fran / Bassiri, Hamid / Odom John, Audrey R

medRxiv : the preprint server for health sciences

2024

Abstract: Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to ... ...

Abstract	Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVβ21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.
Language	English
Publishing date	2024-01-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.11.24301110
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Article ; Online: Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8

Harabuchi, Shohei / Khan, Omar / Bassiri, Hamid / Yoshida, Taku / Okada, Yohei / Takizawa, Masaomi / Ikeda, Osamu / Katada, Akihiro / Kambayashi, Taku

Frontiers in immunology

2022 Volume 13, Page(s) 1032113

Abstract: Introduction: Activation of T cell receptor (TCR) signaling is critical for clonal expansion of CD8+ T cells. However, the effects of augmenting TCR signaling during chronic antigen exposure is less understood. Here, we investigated the role of ... ...

Abstract	Introduction: Activation of T cell receptor (TCR) signaling is critical for clonal expansion of CD8+ T cells. However, the effects of augmenting TCR signaling during chronic antigen exposure is less understood. Here, we investigated the role of diacylglycerol (DAG)-mediated signaling downstream of the TCR during chronic lymphocytic choriomeningitis virus clone 13 (LCMV CL13) infection by blocking DAG kinase zeta (DGKζ), a negative regulator of DAG. Methods: We examined the activation, survival, expansion, and phenotype of virus-specific T cell in the acute and chronic phases of LCMV CL13-infected in mice after DGKζ blockade or selective activation of ERK. Results: Upon LCMV CL13 infection, DGKζ deficiency promoted early short-lived effector cell (SLEC) differentiation of LCMV-specific CD8+ T cells, but this was followed by abrupt cell death. Short-term inhibition of DGKζ with ASP1570, a DGKζ-selective pharmacological inhibitor, augmented CD8+ T cell activation without causing cell death, which reduced virus titers both in the acute and chronic phases of LCMV CL13 infection. Unexpectedly, the selective enhancement of ERK, one key signaling pathway downstream of DAG, lowered viral titers and promoted expansion, survival, and a memory phenotype of LCMV-specific CD8+ T cells in the acute phase with fewer exhausted T cells in the chronic phase. The difference seen between DGKζ deficiency and selective ERK enhancement could be potentially explained by the activation of the AKT/mTOR pathway by DGKζ deficiency, since the mTOR inhibitor rapamycin rescued the abrupt cell death seen in virus-specific DGKζ KO CD8+ T cells. Discussion: Thus, while ERK is downstream of DAG signaling, the two pathways lead to distinct outcomes in the context of chronic CD8+ T cell activation, whereby DAG promotes SLEC differentiation and ERK promotes a memory phenotype.
MeSH term(s)	Animals ; Mice ; CD8-Positive T-Lymphocytes ; Diglycerides/metabolism ; Lymphocytic Choriomeningitis ; Lymphocytic choriomeningitis virus ; Receptors, Antigen, T-Cell ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; MAP Kinase Signaling System
Chemical Substances	Diglycerides ; Receptors, Antigen, T-Cell ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1032113
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Article ; Online: Emapalumab for the treatment of refractory cytokine release syndrome in pediatric patients.

Schuelke, Matthew R / Bassiri, Hamid / Behrens, Edward M / Canna, Scott / Croy, Colleen / DiNofia, Amanda / Gollomp, Kandace / Grupp, Stephan / Lambert, Michele / Lambrix, Arathi / Maude, Shannon L / Myers, Regina / Newman, Haley / Petrosa, Whitney / Seif, Alix / Sullivan, Kathleen E / Teachey, David T / Diorio, Caroline

Blood advances

2023 Volume 7, Issue 18, Page(s) 5603–5607

MeSH term(s)	Humans ; Child ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/etiology ; Antibodies, Monoclonal/adverse effects ; Antibodies, Neutralizing
Chemical Substances	Emapalumab ; Antibodies, Monoclonal ; Antibodies, Neutralizing
Language	English
Publishing date	2023-09-18
Publishing country	United States
Document type	Research Support, Non-U.S. Gov't ; Letter
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010712
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Article ; Online: Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells.

McNerney, Kevin O / Karageorgos, Spyridon A / Hogarty, Michael D / Bassiri, Hamid

Frontiers in immunology

2020 Volume 11, Page(s) 873

Abstract: Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care ... ...

Abstract	Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective treatments for this disease. While the monoclonal antibody dinutuximab has demonstrated the potential for immunotherapy to improve overall NB outcomes, the 5-year overall survival of high-risk patients has not yet substantially changed. The frequency and type of invariant natural killer T cells (iNKTs) and natural killer cells (NKs) has been associated with improved outcomes in several solid and liquid malignancies, including NB. Indeed, iNKTs and NKs inhibit tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs), kill cancer stem cells (CSCs) and neuroblasts, and robustly secrete cytokines to recruit additional immune effectors. These capabilities, and promising pre-clinical and early clinical data suggest that iNKT- and NK-based therapies may hold promise as both stand-alone and combination treatments for NB. In this review we will summarize the biologic features of iNKTs and NKs that confer advantages for NB immunotherapy, discuss the barriers imposed by the NB tumor microenvironment, and examine the current state of such therapies in pre-clinical models and clinical trials.
MeSH term(s)	Animals ; Child ; Clinical Trials as Topic ; Disease Models, Animal ; Humans ; Immunotherapy, Adoptive/methods ; Killer Cells, Natural/immunology ; Killer Cells, Natural/transplantation ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/transplantation ; Neuroblastoma/therapy ; Tumor Microenvironment
Language	English
Publishing date	2020-05-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2020.00873
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children.

Chang, Joyce C / Matsubara, Daisuke / Morgan, Ryan W / Diorio, Caroline / Nadaraj, Sumekala / Teachey, David T / Bassiri, Hamid / Behrens, Edward M / Banerjee, Anirban

Journal of the American Heart Association

2021 Volume 10, Issue 16, Page(s) e021428

Abstract: Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine ...

Abstract	Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS-C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive-inotropic requirements. Compared with controls, cases with MIS-C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS-C had abnormal left ventricular function (
MeSH term(s)	Adolescent ; Age Factors ; Atrial Function, Left ; Biomarkers/blood ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/immunology ; Child ; Cross-Sectional Studies ; Cytokine Release Syndrome/diagnosis ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/immunology ; Cytokines/blood ; Echocardiography ; Female ; Heart Diseases/diagnostic imaging ; Heart Diseases/etiology ; Heart Diseases/immunology ; Heart Diseases/physiopathology ; Humans ; Inflammation Mediators/blood ; Male ; Prognosis ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Systemic Inflammatory Response Syndrome/complications ; Systemic Inflammatory Response Syndrome/diagnosis ; Systemic Inflammatory Response Syndrome/immunology ; Ventricular Function, Left ; Ventricular Function, Right
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators
Language	English
Publishing date	2021-08-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.121.021428
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 3502 Stimulating iNKT Cell-Mediated Neuroblastoma Cytotoxicity in a Mouse Model

Kevin Owen McNerney / Hamid Bassiri / Spyridon Karageorgos / Priya Khurana

Journal of Clinical and Translational Science, Vol 3, Pp 21-

2019 Volume 21

Abstract: OBJECTIVES/SPECIFIC AIMS: Overall Research Aim: To develop an iNKT-cell engaging reagent (“CAb”)to induce neuroblastoma-directed cytotoxicity in vitro and in a mouse model of neuroblastoma. Objective 1: Explore the contribution of different GD2 ... ...

Abstract	OBJECTIVES/SPECIFIC AIMS: Overall Research Aim: To develop an iNKT-cell engaging reagent (“CAb”)to induce neuroblastoma-directed cytotoxicity in vitro and in a mouse model of neuroblastoma. Objective 1: Explore the contribution of different GD2 affinities to the cytotoxicity against neuroblastoma cells in vitro. Objective 2: Deteremine whether use of different stimulatory glycolipids (alpha-GalCer vs. C34) alter the activation and cytotoxicity of iNKT cells against neuroblastoma in vitro. Objective 3: To analyze survival of an immunocompetent mouse model of neuroblastoma treated with C34-loaded vs alpha-GalCer-loaded CAb molecule, and to analyze the tumor microenvironment in each treatment condition. METHODS/STUDY POPULATION: CAb molecule will be generated by fusing a CD1d protein to an scFv domain for GD2 using cloning techniques. Previous work by our group has used a streptavidin-biotin system to link CD1d to an antibody against GD2, which is large and immunogenic. Protein expression of this novel fusion protein will occur in HEK293 cells. This new CAb molecule will then be loaded with alpha-GalCer or C34 for use in cytotoxicity and in vivo experiments. Cytotoxicity Assessment: Chromium assays will be used to assess the specific cytotoxicity generated by iNKT cells against neuroblastoma cells in vitro. iNKT cells will be activated by “CAb’s” with relatively high and low affinity for GD2, and also with Alpha-GalCer and C34 glycolipid antigen. flow cytometry will be used to assess for CD107a and Interferon Gamma. Mouse Model of Neuroblastoma: TH-MYCN +/+ mice will be used as an immunocompetent model of neuroblastoma. These mice have the MYCN gene under the control of a tyrosine hydroxylase promoter, and spontaneously develop neuroblastomas by 2 weeks of life which are uniformly fatal by 8 weeks of life. In vivo survival studies will be conducted by injecting CAb of relatively high and low affinity, loaded with glycolipid antigen intraperitonealy into TH-MYCN+/+ mice starting at 2 weeks of age, twice weekly. ...
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intravenous colistin use for infections due to MDR Gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis.

Karageorgos, Spyridon A / Bassiri, Hamid / Siakallis, George / Miligkos, Michael / Tsioutis, Constantinos

The Journal of antimicrobial chemotherapy

2019 Volume 74, Issue 9, Page(s) 2497–2506

Abstract: Background: Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs).: Methods: Systematic review of intravenous colistin ... ...

Abstract	Background: Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs). Methods: Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018). Results: Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%-38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%-21.5%). Conclusions: While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.
MeSH term(s)	Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii/drug effects ; Administration, Intravenous ; Adolescent ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/pharmacology ; Child ; Child, Preschool ; Colistin/administration & dosage ; Colistin/adverse effects ; Colistin/pharmacokinetics ; Critical Illness ; Drug Resistance, Multiple, Bacterial ; Female ; Gram-Negative Bacteria/drug effects ; Gram-Negative Bacterial Infections/drug therapy ; Gram-Negative Bacterial Infections/microbiology ; Humans ; Intensive Care Units, Pediatric ; Male
Chemical Substances	Anti-Bacterial Agents ; Colistin (Z67X93HJG1)
Language	English
Publishing date	2019-04-30
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkz165
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