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Article ; Online: Targeting necroptosis for the treatment of myositis.

Nagaraju, Kanneboyina / Morales, Melissa

2022 Volume 18, Issue 6, Page(s) 307–308

MeSH term(s)	Humans ; Myositis/drug therapy ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
Chemical Substances	Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-022-00775-7
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Article ; Online: Terence A Partridge: A career dedicated to pursuit of curiosity, mentorship, and secrets of skeletal muscle stem cells.

Jaiswal, Jyoti K / Nagaraju, Kanneboyina / Morgan, Jennifer

Journal of neuromuscular diseases

2021 Volume 8, Issue s2, Page(s) S173–S179

MeSH term(s)	Exploratory Behavior ; History, 20th Century ; History, 21st Century ; Humans ; Mentors ; Muscle, Skeletal ; Neuromuscular Diseases/history ; Stem Cells
Language	English
Publishing date	2021-12-01
Publishing country	Netherlands
Document type	Biography ; Editorial ; Historical Article ; Portrait
ISSN	2214-3602
ISSN (online)	2214-3602
DOI	10.3233/JND-219010
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Article ; Online: Loss of calpain3b in Zebrafish, a Model of Limb-Girdle Muscular Dystrophy, Increases Susceptibility to Muscle Defects Due to Elevated Muscle Activity

Prykhozhij, Sergey V. / Cáceres, Lucía / Ban, Kevin / Cordeiro-Santanach, Anna / Nagaraju, Kanneboyina / Hoffman, Eric P. / Berman, Jason N.

Genes (Basel). 2023 Feb. 15, v. 14, no. 2

2023

Abstract: Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1; formerly LGMD2A), characterized by progressive hip and shoulder muscle weakness, is caused by mutations in CAPN3. In zebrafish, capn3b mediates Def-dependent degradation of p53 in the liver and intestines. ... ...

Abstract	Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1; formerly LGMD2A), characterized by progressive hip and shoulder muscle weakness, is caused by mutations in CAPN3. In zebrafish, capn3b mediates Def-dependent degradation of p53 in the liver and intestines. We show that capn3b is expressed in the muscle. To model LGMDR1 in zebrafish, we generated three deletion mutants in capn3b and a positive-control dmd mutant (Duchenne muscular dystrophy). Two partial deletion mutants showed transcript-level reduction, whereas the RNA-less mutant lacked capn3b mRNA. All capn3b homozygous mutants were developmentally-normal adult-viable animals. Mutants in dmd were homozygous-lethal. Bathing wild-type and capn3b mutants in 0.8% methylcellulose (MC) for 3 days beginning 2 days post-fertilization resulted in significantly pronounced (20–30%) birefringence-detectable muscle abnormalities in capn3b mutant embryos. Evans Blue staining for sarcolemma integrity loss was strongly positive in dmd homozygotes, negative in wild-type embryos, and negative in MC-treated capn3b mutants, suggesting membrane instability is not a primary muscle pathology determinant. Increased birefringence-detected muscle abnormalities in capn3b mutants compared to wild-type animals were observed following induced hypertonia by exposure to cholinesterase inhibitor, azinphos-methyl, reinforcing the MC results. These mutant fish represent a novel tractable model for studying the mechanisms underlying muscle repair and remodeling, and as a preclinical tool for whole-animal therapeutics and behavioral screening in LGMDR1.
Keywords	Danio rerio ; azinphos-methyl ; cholinesterase ; hips ; homozygosity ; liver ; methylcellulose ; models ; muscles ; muscular dystrophy ; mutants ; therapeutics
Language	English
Dates of publication	2023-0215
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14020492
Database	NAL-Catalogue (AGRICOLA)

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Article: Death and Disability Reported with Cases of Vaccine Anaphylaxis Stratified by Administration Setting: An Analysis of the Vaccine Adverse Event Reporting System from 2017 to 2022.

Klosko, Rachel C / Lynch, Sarah E / Cabral, Danielle L / Nagaraju, Kanneboyina / Johnston, Yvonne A / Steinberg, Joshua D / McCall, Kenneth L

Vaccines

2023 Volume 11, Issue 2

Abstract: The serious nature of post-vaccination anaphylaxis requires healthcare professionals to be adequately trained to respond to these hypersensitivity emergencies. The aim of this study was to compare outcomes reported with cases of vaccine anaphylaxis ... ...

Abstract	The serious nature of post-vaccination anaphylaxis requires healthcare professionals to be adequately trained to respond to these hypersensitivity emergencies. The aim of this study was to compare outcomes reported with cases of vaccine anaphylaxis stratified by administration setting. We queried reports in the Vaccine Adverse Event Reporting System (VAERS) database from 2017 to 2022 and identified cases involving anaphylaxis with an onset within one day of vaccine administration. The primary outcome was the combined prevalence of death or disability for each setting while the secondary outcome was the prevalence of hospitalization. Adjusted (age, sex, prior history of allergy, vaccine type) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis. A total of 2041 cases of anaphylaxis comprised the primary study cohort with representation in the sample from all 50 US states and the District of Columbia. The mean age was 43.3 ± 17.5 years, and most cases involved women (79.9%). Cases of anaphylaxis were reported after receiving a coronavirus vaccine (85.2%), influenza vaccine (5.9%), tetanus vaccine (2.2%), zoster vaccine (1.6%), measles vaccine (0.7%), and other vaccine (4.5%). Outcomes associated with reports of vaccine anaphylaxis included 35 cases of death and disability and 219 hospitalizations. Compared with all other settings, the aOR of death and disability when anaphylaxis occurred was 1.92 (95% CI, 0.86-4.54) in a medical provider's office, 0.85 (95% CI, 0.26-2.43) in a pharmacy and 1.01 (95% CI, 0.15-3.94) in a public health clinic. Compared with all other settings, the aOR of hospitalization when anaphylaxis occurred was 1.02 (95% CI, 0.71-1.47) in a medical provider's office, 1.06 (95% CI, 0.72-1.54) in a pharmacy, and 1.12 (95% CI, 0.61-1.93) in a public health clinic. An analysis of a national database across six years revealed no significant differences in the odds of death/disability and odds of hospitalization associated with post-vaccination anaphylaxis in the medical office, pharmacy, and public health clinic compared with all other settings. This study expands our understanding of the safety of immunization services and reinforces that all settings must be prepared to respond to such an emergency.
Language	English
Publishing date	2023-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11020276
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Article ; Online: Loss of

Prykhozhij, Sergey V / Caceres, Lucia / Ban, Kevin / Cordeiro-Santanach, Anna / Nagaraju, Kanneboyina / Hoffman, Eric P / Berman, Jason N

Genes

2023 Volume 14, Issue 2

Abstract: Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1; formerly LGMD2A), characterized by progressive hip and shoulder muscle weakness, is caused by mutations ... ...

Abstract	Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1; formerly LGMD2A), characterized by progressive hip and shoulder muscle weakness, is caused by mutations in
MeSH term(s)	Animals ; Zebrafish/genetics ; Muscular Dystrophies, Limb-Girdle/genetics ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/pathology
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14020492
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Article ; Online: A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state.

Roy, Runia / Dang, Utkarsh J / Huffman, Kim M / Alayi, Tchilabalo / Hathout, Yetrib / Nagaraju, Kanneboyina / Visich, Paul S / Hoffman, Eric P

Psychoneuroendocrinology

2023 Volume 159, Page(s) 106411

Abstract: Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, ... ...

Abstract	Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. Methods: The Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012-2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m Findings: Upon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM > PM [-4.02 fold; p < 0.001]; IL-8 AM > PM [-1.36 fold; p < 0.001]; IL-6 AM < PM [+1.49 fold; p < 0.001]; TNF-α AM < PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10 Interpretation: We provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks.
MeSH term(s)	Humans ; Child ; Hydrocortisone ; Longitudinal Studies ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Cross-Sectional Studies ; Interleukin-8 ; Internet ; Circadian Rhythm/physiology ; Saliva
Chemical Substances	Hydrocortisone (WI4X0X7BPJ) ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Interleukin-8
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2023.106411
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Article ; Online: Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis.

Morales, Melissa / Alayi, Tchilabalo D / Tawalbeh, Shefa M / Sydenstricker, Agnes V / Spathis, Rita / Kim, Hanna / Nagaraju, Kanneboyina / Hathout, Yetrib / Rider, Lisa G

Rheumatology (Oxford, England)

2023 Volume 62, Issue 9, Page(s) 3161–3168

Abstract: Objectives: To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach.: Methods: First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects ( ...

Abstract	Objectives: To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach. Methods: First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects (n = 21) and processed for analysis using a standardized liquid chromatography-tandem mass spectrometry approach. Biomarkers with significantly altered levels were correlated with clinical measures of myositis disease activity and damage. A subset of candidate biomarkers was validated using commercially available ELISA kits. Results: In total, 2348 proteins were detected in the samples, with 275 proteins quantified across all samples. Among the differentially altered proteins, cathepsin D and galectin-3 binding protein were significantly increased in the urine of JDM patients (adjusted P < 0.05), supporting previous findings in myositis patients. These two candidate biomarkers were confirmed with ELISAs. Cathepsin D positively correlated with Myositis Damage Index (r = 0.57, P < 0.05) and negatively correlated with the Childhood Myositis Assessment Scale (r = -0.54, P < 0.05). We also identified novel JDM candidate biomarkers involved with key features of myositis, including extracellular matrix remodelling proteins. Conclusion: This study confirmed the presence of several proteins in the urine of JDM patients that were previously found to be elevated in the blood of myositis patients and identified novel candidate biomarkers that require validation. These results support the use of urine as a source for biomarker development in JDM.
MeSH term(s)	Humans ; Child ; Dermatomyositis ; Cathepsin D ; Proteomics ; Myositis ; Mass Spectrometry
Chemical Substances	Cathepsin D (EC 3.4.23.5)
Language	English
Publishing date	2023-01-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead033
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Article ; Online: Characterization of the dystrophin-associated protein complex by mass spectrometry.

Canessa, Emily H / Spathis, Rita / Novak, James S / Beedle, Aaron / Nagaraju, Kanneboyina / Bello, Luca / Pegoraro, Elena / Hoffman, Eric P / Hathout, Yetrib

Mass spectrometry reviews

2022 Volume 43, Issue 1, Page(s) 90–105

Abstract: The dystrophin-associated protein complex (DAPC) is a highly organized multiprotein complex that plays a pivotal role in muscle fiber structure integrity and cell signaling. The complex is composed of three distinct interacting subgroups, intracellular ... ...

Abstract	The dystrophin-associated protein complex (DAPC) is a highly organized multiprotein complex that plays a pivotal role in muscle fiber structure integrity and cell signaling. The complex is composed of three distinct interacting subgroups, intracellular peripheral proteins, transmembrane glycoproteins, and extracellular glycoproteins subcomplexes. Dystrophin protein nucleates the DAPC and is important for connecting the intracellular actin cytoskeletal filaments to the sarcolemma glycoprotein complex that is connected to the extracellular matrix via laminin, thus stabilizing the sarcolemma during muscle fiber contraction and relaxation. Genetic mutations that lead to lack of expression or altered expression of any of the DAPC proteins are associated with different types of muscle diseases. Hence characterization of this complex in healthy and dystrophic muscle might bring insights into its role in muscle pathogenesis. This review highlights the role of mass spectrometry in characterizing the DAPC interactome as well as post-translational glycan modifications of some of its components such as α-dystroglycan. Detection and quantification of dystrophin using targeted mass spectrometry are also discussed in the context of healthy versus dystrophic skeletal muscle.
MeSH term(s)	Dystrophin/analysis ; Dystrophin/genetics ; Dystrophin/metabolism ; Dystrophin-Associated Protein Complex/analysis ; Dystrophin-Associated Protein Complex/metabolism ; Laminin/analysis ; Laminin/metabolism ; Sarcolemma/chemistry ; Sarcolemma/metabolism ; Muscle, Skeletal/chemistry ; Muscle, Skeletal/metabolism ; Glycoproteins/analysis
Chemical Substances	Dystrophin ; Dystrophin-Associated Protein Complex ; Laminin ; Glycoproteins
Language	English
Publishing date	2022-11-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1491946-1
ISSN	1098-2787 ; 0277-7037
ISSN (online)	1098-2787
ISSN	0277-7037
DOI	10.1002/mas.21823
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Article: Role of major histocompatibility complex class I molecules in autoimmune myositis.

Nagaraju, Kanneboyina

Current opinion in rheumatology

2005 Volume 17, Issue 6, Page(s) 725–730

Abstract: Purpose of review: Recent work has continued to clarify the role of major histocompatibility complex class I in the pathogenesis of autoimmune myositis. In the past year, several new observations have been made in this area. This review describes these ... ...

Abstract	Purpose of review: Recent work has continued to clarify the role of major histocompatibility complex class I in the pathogenesis of autoimmune myositis. In the past year, several new observations have been made in this area. This review describes these findings and discusses their relevance to the pathogenesis of autoimmune myositis. Recent findings: Recent studies have confirmed earlier observations of the up-regulation of major histocompatibility complex class I antigens in myositis. In particular, a recent study has strengthened the conclusion that major histocompatibility complex class I expression is highly specific to inflammatory myopathies and may be of diagnostic value. Two new studies have indicated that endoplasmic reticulum stress response pathway (the endoplasmic reticulum overload [NF-kB] and unfolded protein response [GRP78]) are highly activated in patients with myositis. One study using transgenic mice has further indicated that abnormal accumulation of major histocompatibility complex class I in the endoplasmic reticulum of muscle may be responsible for the initiation of this endoplasmic reticulum stress response. Furthermore, studies of normal muscle cells have shown that endoplasmic reticulum stress also plays an important role in skeletal muscle development. Investigations of autoantigen expression in myositis biopsies have revealed that regenerating muscle cells express high levels of autoantigens and major histocompatibility complex class I, indicating that these cells are the targets of cytotoxic T-cell attack and may participate in the initiation of a myositis-specific autoimmune response. Summary: Defining the role of major histocompatibility complex class I in autoimmune myositis may be useful not only for diagnosis of this group of diseases but also for therapeutic opportunities for these difficult disorders.
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Histocompatibility Antigens Class I/physiology ; Humans ; Myositis/immunology
Chemical Substances	Histocompatibility Antigens Class I
Language	English
Publishing date	2005-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1045317-9
ISSN	1531-6963 ; 1040-8711
ISSN (online)	1531-6963
ISSN	1040-8711
DOI	10.1097/01.bor.0000179947.58271.9a
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Article ; Online: Risk factors and disease mechanisms in myositis.

Miller, Frederick W / Lamb, Janine A / Schmidt, Jens / Nagaraju, Kanneboyina

Nature reviews. Rheumatology

2018 Volume 14, Issue 5, Page(s) 255–268

Abstract: Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic ... ...

Abstract	Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic processes in the various idiopathic inflammatory myopathy (IIM) phenotypes (known collectively as myositis) have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in some populations, and several genetic variants associated with other autoimmune diseases have been identified as IIM risk factors. Environmental risk factors are less well studied than genetic factors but might include viruses, bacteria, ultraviolet radiation, smoking, occupational and perinatal exposures and a growing list of drugs (including biologic agents) and dietary supplements. Disease mechanisms vary by phenotype, with evidence of shared innate and adaptive immune and metabolic pathways in some phenotypes but unique pathways in others. The heterogeneity and rarity of the IIMs make advancements in diagnosis and treatment cumbersome. Novel approaches, better-defined phenotypes, and international, multidisciplinary consensus have contributed to progress, and it is hoped that these methods will eventually enable therapeutic intervention before the onset or major progression of disease. In the future, preemptive strategies for IIM management might be possible.
MeSH term(s)	Disease Management ; Environmental Exposure/adverse effects ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; HLA Antigens/genetics ; Haplotypes ; Humans ; Myositis/etiology ; Myositis/genetics ; Phenotype
Chemical Substances	HLA Antigens
Language	English
Publishing date	2018-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/nrrheum.2018.48
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