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Article ; Online: Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Cohen, Jessica / Mathew, Annette / Dourvetakis, Kirk D / Sanchez-Guerrero, Estella / Pangeni, Rajendra P / Gurusamy, Narasimman / Aenlle, Kristina K / Ravindran, Geeta / Twahir, Assma / Isler, Dylan / Sosa-Garcia, Sara Rukmini / Llizo, Axel / Bested, Alison C / Theoharides, Theoharis C / Klimas, Nancy G / Kempuraj, Duraisamy

Cells

2024 Volume 13, Issue 6

Abstract: Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the ... ...

Abstract	Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.
MeSH term(s)	Humans ; Neuroinflammatory Diseases ; Endothelial Cells ; Induced Pluripotent Stem Cells ; Neurodegenerative Diseases ; Inflammation
Language	English
Publishing date	2024-03-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13060511
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Article ; Online: Molecular Phenotypes of Acute Respiratory Distress Syndrome in the ROSE Trial Have Differential Outcomes and Gene Expression Patterns That Differ at Baseline and Longitudinally over Time.

Sinha, Pratik / Neyton, Lucile / Sarma, Aartik / Wu, Nelson / Jones, Chayse / Zhuo, Hanjing / Liu, Kathleen D / Sanchez Guerrero, Estella / Ghale, Rajani / Love, Christina / Mick, Eran / Delucchi, Kevin L / Langelier, Charles R / Thompson, B Taylor / Matthay, Michael A / Calfee, Carolyn S

American journal of respiratory and critical care medicine

2024 Volume 209, Issue 7, Page(s) 816–828

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Humans ; Phenotype ; Biomarkers ; Respiratory Distress Syndrome ; Blood Proteins/genetics ; Gene Expression
Chemical Substances	Biomarkers ; Blood Proteins
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202308-1490OC
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Article ; Online: In host evolution of beta lactam resistance during active treatment for

Spottiswoode, Natasha / Hao, Samantha / Sanchez-Guerrero, Estella / Detweiler, Angela M / Mekonen, Honey / Neff, Norma / Macmillan, Henriette / Schwartz, Brian S / Engel, Joanne / DeRisi, Joseph L / Miller, Steven A / Langelier, Charles R

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1241608

Abstract: Multidrug-resistant (MDR) ...

Abstract	Multidrug-resistant (MDR)
MeSH term(s)	United States ; Humans ; Pseudomonas aeruginosa/genetics ; beta-Lactam Resistance ; Carbapenems ; Sepsis ; Bacteremia/drug therapy
Chemical Substances	Carbapenems
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1241608
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Article ; Online: Whole-genome sequencing rule-out of suspected hospital-onset

Chu, Victoria T / Nafees, Saba / Waltari, Eric / McNeil, Nicole / Caughell, Carolyn / Sanchez-Guerrero, Estella / Wang, Lusha / Stanley, Kim / Cunningham, Gail / Wong, Joan / Phelps, Maíra / Tato, Cristina M / Miller, Steve / DeRisi, Joseph L / Yokoe, Deborah S / Ramirez-Avila, Lynn / Langelier, Charles R

Infection control and hospital epidemiology

2023 Volume 44, Issue 12, Page(s) 2059–2061

Abstract: Two independent temporal-spatial clusters of hospital- ... ...

Abstract	Two independent temporal-spatial clusters of hospital-onset
MeSH term(s)	Humans ; Rhizopus/genetics ; Phylogeny ; Genome, Bacterial ; Hospitals ; Disease Outbreaks
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2023.85
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Article ; Online: A 2-Gene Host Signature for Improved Accuracy of COVID-19 Diagnosis Agnostic to Viral Variants.

Albright, Jack / Mick, Eran / Sanchez-Guerrero, Estella / Kamm, Jack / Mitchell, Anthea / Detweiler, Angela M / Neff, Norma / Tsitsiklis, Alexandra / Hayakawa Serpa, Paula / Ratnasiri, Kalani / Havlir, Diane / Kistler, Amy / DeRisi, Joseph L / Pisco, Angela Oliveira / Langelier, Charles R

mSystems

2022 Volume 8, Issue 1, Page(s) e0067122

Abstract: The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false-negative viral PCR test results. Such tests are also susceptible to false-positive results due to trace contamination from high viral titer samples. Host immune ...

Abstract	The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false-negative viral PCR test results. Such tests are also susceptible to false-positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses, and nonviral conditions (
MeSH term(s)	Humans ; COVID-19/diagnosis ; SARS-CoV-2/genetics ; COVID-19 Testing ; Pandemics ; Sensitivity and Specificity
Language	English
Publishing date	2022-12-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-5077
ISSN (online)	2379-5077
DOI	10.1128/msystems.00671-22
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Article ; Online: Extracellular signal-regulated kinase-1 phosphorylates early growth response-1 at serine 26.

Santiago, Fernando S / Sanchez-Guerrero, Estella / Zhang, Guishui / Zhong, Ling / Raftery, Mark J / Khachigian, Levon M

Biochemical and biophysical research communications

2019 Volume 510, Issue 3, Page(s) 345–351

Abstract: Egr-1, an immediate-early gene product and master regulator was originally described as a phosphoprotein following its discovery in the 1980s. However specific residue(s) phosphorylated in Egr-1 remain elusive. Here we phosphorylated recombinant Egr-1 in ...

Abstract	Egr-1, an immediate-early gene product and master regulator was originally described as a phosphoprotein following its discovery in the 1980s. However specific residue(s) phosphorylated in Egr-1 remain elusive. Here we phosphorylated recombinant Egr-1 in vitro with ERK1 prior to mass spectrometry, which identified phosphorylation of Ser
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies, Monoclonal ; Cells, Cultured ; Early Growth Response Protein 1/chemistry ; Early Growth Response Protein 1/immunology ; Early Growth Response Protein 1/metabolism ; Immunoprecipitation ; Mass Spectrometry ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Rats ; Sequence Alignment ; Serine/metabolism
Chemical Substances	Antibodies, Monoclonal ; Early Growth Response Protein 1 ; Egr1 protein, mouse ; Egr1 protein, rat ; Serine (452VLY9402) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
Language	English
Publishing date	2019-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2019.01.019
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Article ; Online: Prolonged silent carriage, genomic virulence potential and transmission between staff and patients characterize a neonatal intensive care unit (NICU) outbreak of methicillin-resistant

Madera, Sharline / McNeil, Nicole / Serpa, Paula Hayakawa / Kamm, Jack / Pak, Christy / Caughell, Carolyn / Nichols, Amy / Dynerman, David / Li, Lucy M / Sanchez-Guerrero, Estella / Phelps, Maira S / Detweiler, Angela M / Neff, Norma / Reyes, Helen / Miller, Steve A / Yokoe, Deborah S / DeRisi, Joseph L / Ramirez-Avila, Lynn / Langelier, Charles R

Infection control and hospital epidemiology

2022 Volume 44, Issue 1, Page(s) 40–46

Abstract: Background: Methicillin-resistant : Objective: Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority.: Methods: We investigated a cluster of clinical MRSA cases in the ... ...

Abstract	Background: Methicillin-resistant Objective: Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority. Methods: We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP). Results: Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events. Conclusions: Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.
MeSH term(s)	Infant, Newborn ; Infant ; Humans ; Methicillin-Resistant Staphylococcus aureus/genetics ; Intensive Care Units, Neonatal ; Cross Infection/epidemiology ; Staphylococcal Infections/prevention & control ; Virulence/genetics ; Prospective Studies ; Phylogeny ; Disease Outbreaks/prevention & control ; Infection Control/methods ; Genomics
Language	English
Publishing date	2022-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2022.48
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Article ; Online: A 2-Gene Host Signature for Improved Accuracy of COVID-19 Diagnosis Agnostic to Viral Variants

medRxiv

Abstract: The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false negative viral PCR test results. Such tests are also susceptible to false positive results due to trace contamination from high viral titer samples. Host immune ...

Abstract	The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false negative viral PCR test results. Such tests are also susceptible to false positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses and non-viral conditions (n=318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to predict COVID-19. Optimal classifiers achieve an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n=553). We show that a classifier relying on a single interferon-stimulated gene, such as IFI6 or IFI44, measured in RT-qPCR assays (n=144) achieves AUC values as high as 0.88. Addition of a second gene, such as GBP5, significantly improves the specificity compared to other respiratory viruses. The performance of a clinically practical 2-gene RT-qPCR classifier is robust across common SARS-CoV-2 variants, including Omicron, and is unaffected by cross-contamination, demonstrating its utility for improving accuracy of COVID-19 diagnostics.
Keywords	covid19
Language	English
Publishing date	2022-01-07
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.01.06.21268498
Database	COVID19

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Article ; Online: Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-dependent Egr-1 transactivation.

Sanchez-Guerrero, Estella / Midgley, Valerie C / Khachigian, Levon M

Nucleic acids research

2008 Volume 36, Issue 6, Page(s) 1941–1951

Abstract: Platelet-derived growth factors are a family of mitogens and chemoattractants comprising of four ligand genes (A-, B-, C-, D-chains) implicated in many physiologic and pathophysiologic processes, including atherosclerosis, fibrosis and tumorigenesis. Our ...

Abstract	Platelet-derived growth factors are a family of mitogens and chemoattractants comprising of four ligand genes (A-, B-, C-, D-chains) implicated in many physiologic and pathophysiologic processes, including atherosclerosis, fibrosis and tumorigenesis. Our understanding of the molecular mechanisms, which regulate PDGF-C transcription remains incomplete. Transient transfection analysis, conventional and quantitative real-time PCR revealed the induction of PDGF-C transcription and mRNA expression in smooth muscle cells (SMCs) exposed to the peptide hormone angiotensin (ATII), which induces Egr-1. Occupancy of a G + C-rich element in the proximal region of the PDGF-C promoter was unaffected by ATII. Instead we discovered, using both nuclear extracts and recombinant proteins with EMSA and ChIP analyses, the existence of a second Egr-1-binding element located 500 bp upstream. ATII induction of PDGF-C transcription is mediated by the angiotensin type 1 receptor (AT1R) and Egr-1 activation through this upstream element. DNAzyme ED5 targeting Egr-1 blocked ATII-inducible PDGF-C expression. Moreover, increased PDGF-C expression after exposure to ATII depends upon the differentiation state of the SMCs. This study demonstrates the existence of this novel ATII-AT1R-Egr-1-PDGF-C axis in SMCs of neonatal origin, but not in adult SMCs, where ATII induces Egr-1 but not PDGF-C.
MeSH term(s)	Angiotensin II/pharmacology ; Animals ; Base Sequence ; Binding Sites ; Cells, Cultured ; Early Growth Response Protein 1/metabolism ; Gene Expression ; Lymphokines/biosynthesis ; Lymphokines/genetics ; Molecular Sequence Data ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Platelet-Derived Growth Factor/biosynthesis ; Platelet-Derived Growth Factor/genetics ; Promoter Regions, Genetic ; Rats ; Receptor, Angiotensin, Type 1/metabolism ; Transcriptional Activation
Chemical Substances	Early Growth Response Protein 1 ; Lymphokines ; Platelet-Derived Growth Factor ; Receptor, Angiotensin, Type 1 ; platelet-derived growth factor C ; Angiotensin II (11128-99-7)
Language	English
Publishing date	2008-02-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkm923
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Article ; Online: Repression of PDGF-R-α after cellular injury involves TNF-α, formation of a c-Fos-YY1 complex, and negative regulation by HDAC.

Zhang, Ning / Chan, Cecilia W S / Sanchez-Guerrero, Estella / Khachigian, Levon M

American journal of physiology. Cell physiology

2012 Volume 302, Issue 11, Page(s) C1590–8

Abstract: Wound healing is a complex dynamic process involving a variety of cell types, including fibroblasts that express and respond to cytokines and growth factors in the local microenvironment. The mechanisms controlling gene expression after injury at a ... ...

Abstract	Wound healing is a complex dynamic process involving a variety of cell types, including fibroblasts that express and respond to cytokines and growth factors in the local microenvironment. The mechanisms controlling gene expression after injury at a transcriptional level are poorly understood. Here we show that decreased expression of a key receptor, PDGF-receptor (R)-α, after fibroblast injury is due to the release and paracrine activity of TNF-α. TNF-α inhibits PDGF-R-α expression and this involves formation of a c-Fos-Yin Yang 1 (YY1) complex and histone deacetylase (HDAC) activity. c-Fos, induced by TNF-α, negatively regulates PDGF-R-α transcription. Small interfering RNA (siRNA) targeting c-Fos or the zinc finger transcription factor YY1 inhibits TNF-α suppression of PDGF-R-α expression. Coimmunoprecipitation studies show that TNF-α stimulates the formation of a complex between c-Fos with YY1. Furthermore, chromatin immunoprecipitation (ChIP) analysis reveals the enrichment of c-Fos, YY1, and HDAC-1 at the PDGF-R-α promoter in cells exposed to TNF-α. With suberoylanilide hydroxamic acid (SAHA) and HDAC-1 siRNA, we demonstrate that HDAC mediates TNF-α repression of PDGF-R-α. These findings demonstrate that transcriptional repression of PDGF-R-α after fibroblast injury involves paracrine activity of endogenous TNF-α, the formation of a c-Fos-YY1 complex, and negative regulatory activity by HDAC.
MeSH term(s)	Animals ; Base Sequence ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Histone Deacetylases/genetics ; Histone Deacetylases/metabolism ; Hydroxamic Acids/metabolism ; Mice ; Molecular Sequence Data ; NIH 3T3 Cells ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-fos/metabolism ; RNA Interference ; RNA, Small Interfering ; Receptor, Platelet-Derived Growth Factor alpha/biosynthesis ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Regulatory Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Tumor Necrosis Factor-alpha/metabolism ; Vorinostat ; YY1 Transcription Factor/genetics ; YY1 Transcription Factor/metabolism
Chemical Substances	DNA-Binding Proteins ; Hydroxamic Acids ; Proto-Oncogene Proteins c-fos ; RNA, Small Interfering ; Tumor Necrosis Factor-alpha ; YY1 Transcription Factor ; YY1 protein, human ; Vorinostat (58IFB293JI) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2012-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00429.2011
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