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Article ; Online: STAT6 joins the gain-of-function club.

Chen, Karin / Ochs, Hans D / Allenspach, Eric J

The Journal of allergy and clinical immunology

2023 Volume 152, Issue 1, Page(s) 53–55

MeSH term(s)	Humans ; Gain of Function Mutation ; Asthma ; Dermatitis, Atopic ; STAT6 Transcription Factor/genetics
Chemical Substances	STAT6 Transcription Factor ; STAT6 protein, human
Language	English
Publishing date	2023-05-14
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.05.003
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Article ; Online: Electrophoretic deposition of dielectric film on stimulation electrodes for the use in intraoperative neuromonitoring

Chen Karin J. / Oswald Johanna / Krüger Thilo

Current Directions in Biomedical Engineering, Vol 4, Iss 1, Pp 521-

2018 Volume 524

Abstract: Electrophoretic deposition (EPD) is a material processing technology which uses direct current (DC) voltage to deposit thin layers on a metallic substrate. EPD is a promising coating technology for medical devices due to its advantages such as thin ... ...

Abstract	Electrophoretic deposition (EPD) is a material processing technology which uses direct current (DC) voltage to deposit thin layers on a metallic substrate. EPD is a promising coating technology for medical devices due to its advantages such as thin homogenous layers and a broad range of usable substrates. The objective of this paper is to demonstrate how EPD can be deployed successfully to apply an insulation layer on a stimulation electrode. The Mapping suction probe by inomed Medizintechnik GmbH, Germany, was coated in this investigation. The unique feature of this product is that it combines both a surgical vacuum and a stimulation probe and is used for brain tumour resection. As for the insulation layer, ethylene chlorotrifluoroethylene (ECTFE) was chosen because of its good dielectric and biocompatible properties. ECTFE particles (Halar®6514, Solvay Specialty Polymer, Italy) were mixed with a solvent (Novec™ 7100DL Engineered Fluid, 3M™) to form a suspension. The coating process was partly automatized to ensure good repeatability and reproducibility. For coating, the stimulation probe was immersed in the suspension so that the counter electrode, a stainless-steel net, surrounded it equidistantly. A heat treatment of the coated device in an oven (FED56, Binder, Germany) was required afterwards to melt the deposited polymer particles. After the heat treatment, a glossy black layer (layer thickness 42 μm) was observed on the substrate. A smooth and homogenous surface confirmed that the coating is suitable for surgical application. However, due to a high evaporation rate of the solvent, the ratio of particles and solvent changes and the coating process will have to be controlled in the future to achieve a stable process. Further advantages of EPD such as short processing time, straightforward process flow and scalability enables high production quantities which is attractive for industrial application. EPD might be a promising coating technology for medical devices in the future.
Keywords	electrophoretic deposition ; insulation layer ; thin film ; medical device ; stimulation electrode ; Medicine ; R
Subject code	620
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	De Gruyter
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Resistin and adenylyl cyclase-associated protein 1 (CAP1) regulate the expression of genes related to insulin resistance in BNL CL.2 mouse liver cells

Avtanski, Dimiter / Chen, Karin / Poretsky, Leonid

Data in Brief. 2019 Aug., v. 25

2019

Abstract: Resistin is an adipokine produced in white adipose tissue that is thought to modulate insulin sensitivity in peripheral tissues (such as liver, skeletal muscle or adipose tissue). Human and murine resistin molecules share only about 60% sequence homology. ...

Abstract	Resistin is an adipokine produced in white adipose tissue that is thought to modulate insulin sensitivity in peripheral tissues (such as liver, skeletal muscle or adipose tissue). Human and murine resistin molecules share only about 60% sequence homology. [1] Contrary to humans, in which resistin is secreted mostly by macrophages, Park and Ahima 2013 resistin in rodents is produced primarily by the mature adipocytes of the white adipose tissue. Although resistin can bind to toll-like receptor 4 (TLF4) activating proinflammatory responses in human and rodents, [3–8] the inflammatory actions of resistin in human monocytes were found to be mediated by resistin binding to adenylyl cyclase-associated protein 1 (CAP1). [9] In this study, we aimed to investigate the in vitro effects of resistin on the expression of various genes related to insulin resistance in mouse liver cells. Using BNL CL.2 cells, we investigated the effect of resistin in untransfected or CAP1 siRNA-transfected cells on the expression of 84 key genes involved in insulin resistance.
Keywords	Toll-like receptor 4 ; adipocytes ; humans ; insulin resistance ; liver ; macrophages ; mice ; monocytes ; resistin ; sequence homology ; skeletal muscle ; white adipose tissue
Language	English
Dates of publication	2019-08
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.104112
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Article ; Online: Resistin and adenylyl cyclase-associated protein 1 (CAP1) regulate the expression of genes related to insulin resistance in BNL CL.2 mouse liver cells.

Avtanski, Dimiter / Chen, Karin / Poretsky, Leonid

Data in brief

2019 Volume 25, Page(s) 104112

Abstract	Resistin is an adipokine produced in white adipose tissue that is thought to modulate insulin sensitivity in peripheral tissues (such as liver, skeletal muscle or adipose tissue). Human and murine resistin molecules share only about 60% sequence homology. [1] Contrary to humans, in which resistin is secreted mostly by macrophages, Park and Ahima 2013 resistin in rodents is produced primarily by the mature adipocytes of the white adipose tissue. Although resistin can bind to toll-like receptor 4 (TLF4) activating proinflammatory responses in human and rodents, [3], [4], [5], [6], [7], [8] the inflammatory actions of resistin in human monocytes were found to be mediated by resistin binding to adenylyl cyclase-associated protein 1 (CAP1). [9] In this study, we aimed to investigate the
Language	English
Publishing date	2019-06-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.104112
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Article ; Online: Development of a Safety Surveillance Plan for the Academic Medicine Sponsor Performing First-in-Human Cellular Therapy Clinical Trials: A Report from the Consortium for Pediatric Cellular Immunotherapy.

Adams, Cheri / Keller, Michael / Michlitsch, Jennifer G / Aguayo-Hiraldo, Paibel / Chen, Karin / Hossain, Mohammad Z / Davis, Ann / Park, Julie R / Verneris, Michael R / Gardner, Rebecca A

Transplantation and cellular therapy

2024 Volume 30, Issue 5, Page(s) 475–487

Abstract: Pharmacovigilance (PV), also known as drug safety, is the science of risk management involving the detection, assessment, understanding, and prevention of adverse effects related to a medication. This discipline has traditionally focused on the ... ...

Abstract	Pharmacovigilance (PV), also known as drug safety, is the science of risk management involving the detection, assessment, understanding, and prevention of adverse effects related to a medication. This discipline has traditionally focused on the postmarketing period, with less attention to early-phase clinical trials. However, during the immunotherapy and cellular therapy investigational stage, regulatory agencies are increasingly emphasizing the need to identify and characterize safety signals earlier in clinical development as part of a comprehensive safety surveillance plan. Compliance with PV and safety regulations are further heightened as cell and gene therapy (CGT) trials grow in complexity and scope owing to ever-changing and increasingly rigorous regulatory mandates. Based on this changing landscape, a critical aspect of early-phase trials of cellular products where significant safety events are anticipated is to ensure that every effort is made to protect clinical trial participants by maximizing attention to the risk-versus-benefit profile. This includes the development of robust plans for safety surveillance that provide a continual assessment of safety signals to enable safety reporting to regulatory bodies and the Food and Drug Administration, a regular analysis of aggregate safety data, and a plan to communicate safety findings. This report focuses on PV in early-phase clinical trials of first-in-human investigational products sponsored by academic centers in which the availability of PV resources and subject matter experts is limited. To more fully understand the challenges of CGT PV oversight within pediatric academic medical centers conducting early-phase clinical trials, a working group from institutions participating in the Consortium for Pediatric Cellular Immunotherapy composed of faculty and regulatory professionals was convened to compare experiences, identify best practices, and review published literature to identify commonalities and opportunities for alignment. Here we present guidelines on PV planning in early-phase CGT clinical trials occurring in academic medical centers and offer strategies to mitigate risk to trial participants. Standards to address regulatory requirements and governance for safety signal identification and risk assessment are discussed.
MeSH term(s)	Humans ; Cell- and Tissue-Based Therapy/standards ; Cell- and Tissue-Based Therapy/methods ; Immunotherapy/adverse effects ; Immunotherapy/legislation & jurisprudence ; Immunotherapy/methods ; Clinical Trials as Topic/legislation & jurisprudence ; Pharmacovigilance ; Product Surveillance, Postmarketing
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2024.02.022
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Zs.A 5082: Show issues

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Article: Cytokine secretion in breast cancer cells – MILLIPLEX assay data

Chen, Karin / Satlof, Leo / Stoffels, Guillaume / Kothapalli, Udithi / Ziluck, Noah / Lema, Maribel / Poretsky, Leonid / Avtanski, Dimiter

Data in Brief. 2020 Feb., v. 28

2020

Abstract: Metastatic breast cancer is the most advanced stage of breast cancer and the leading cause of breast cancer mortality. Although understanding of the cancer progression and metastasis process has improved, the bi-directional communication between the ... ...

Abstract	Metastatic breast cancer is the most advanced stage of breast cancer and the leading cause of breast cancer mortality. Although understanding of the cancer progression and metastasis process has improved, the bi-directional communication between the tumor cell and the tumor microenvironment is still not well understood. Breast cancer cells are highly secretory, and their secretory activity is modulated by a variety of inflammatory stimuli present in the tumor microenvironment. Here, we characterized the cytokine expression in human breast cancer cells (MDA-MB-231, MCF-7, T-47D, and BT-474) in vitro using 41 cytokine MILLIPLEX assay. Further, we compared cytokine expression in breast cancer cells to those in non-tumorigenic human breast epithelial MCF-10A cells.
Keywords	breast neoplasms ; breasts ; cytokines ; epithelium ; humans ; metastasis ; mortality ; neoplasm cells ; neoplasm progression ; secretion
Language	English
Dates of publication	2020-02
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.104798
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Article ; Online: Lymphoma in Partial DiGeorge Syndrome: Report of 2 Cases.

Lozano-Chinga, Michell / Diaz-Cabrera, Natalie / Khimani, Farhad / Chen, Karin / Bohnsack, John / Walter, Jolan E / Tabatabaian, Farnaz / Afify, Zeinab

Journal of pediatric hematology/oncology

2021 Volume 44, Issue 3, Page(s) e819–e822

Abstract: Primary immunodeficiency diseases are associated with an increased tendency for noninfectious complications of autoimmunity and malignancy, particularly leukemia and lymphoma. The mechanisms of immune dysregulation have been linked to the combination of ... ...

Abstract	Primary immunodeficiency diseases are associated with an increased tendency for noninfectious complications of autoimmunity and malignancy, particularly leukemia and lymphoma. The mechanisms of immune dysregulation have been linked to the combination of dysregulated immune cells and environmental factors such as infections. In particular, dysfunction in T-cell subsets and Epstein-Barr virus contributes to the development of autoimmunity and lymphoproliferative disease in primary immunodeficiency diseases. There are scant reports of patients with partial DiGeorge syndrome and Epstein-Barr virus-driven lymphoma. We report 1 patients with partial DiGeorge syndrome who developed lymphoma, and review reported cases in the literature.
MeSH term(s)	DiGeorge Syndrome/complications ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma/complications ; Lymphoproliferative Disorders/complications ; Primary Immunodeficiency Diseases
Language	English
Publishing date	2021-12-28
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/MPH.0000000000002388
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Zs.A 1537: Show issues

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Article ; Online: PEGylated

Verma, Anupam / Chen, Karin / Bender, Cynthia / Gorney, Nathan / Leonard, Whitney / Barnette, Phillip

Pediatric hematology and oncology

2019 Volume 36, Issue 5, Page(s) 277–286

Abstract: Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity ... ...

Abstract	Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.
MeSH term(s)	Adolescent ; Adult ; Asparaginase/administration & dosage ; Asparaginase/adverse effects ; Asparaginase/immunology ; Bacterial Proteins/administration & dosage ; Bacterial Proteins/adverse effects ; Bacterial Proteins/immunology ; Child ; Child, Preschool ; Desensitization, Immunologic ; Drug Hypersensitivity/immunology ; Drug Hypersensitivity/prevention & control ; Escherichia coli/enzymology ; Female ; Humans ; Male ; Pectobacterium chrysanthemi/enzymology ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
Chemical Substances	Bacterial Proteins ; Polyethylene Glycols (3WJQ0SDW1A) ; pegaspargase (7D96IR0PPM) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2019-07-12
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	632914-7
ISSN	1521-0669 ; 0888-0018
ISSN (online)	1521-0669
ISSN	0888-0018
DOI	10.1080/08880018.2019.1634778
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Article ; Online: Chronic Granulomatous Disease With Inflammatory Bowel Disease: Clinical Presentation, Treatment, and Outcomes From the USIDNET Registry.

LaBere, Brenna / Gutierrez, Maria J / Wright, Hannah / Garabedian, Elizabeth / Ochs, Hans D / Fuleihan, Ramsay L / Secord, Elizabeth / Marsh, Rebecca / Sullivan, Kathleen E / Cunningham-Rundles, Charlotte / Notarangelo, Luigi D / Chen, Karin

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 5, Page(s) 1325–1333.e5

Abstract: Background: Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune ... ...

Abstract	Background: Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune diseases. Up to 50% of patients have gastrointestinal (GI) involvement and meet diagnostic criteria for inflammatory bowel disease (CGD-IBD). Objective: We analyzed patients with CGD from the US Immunodeficiency Network (USIDNET) registry to determine whether IBD changes the presentation, treatment, and outcomes of patients with CGD. Methods: A retrospective evaluation of CGD cases from the USIDNET registry was completed. CGD-IBD was defined as the presence of any major physician-reported inflammatory, noninfectious GI disease manifestation. Demographic information, conditions, infections, antimicrobial therapies, immunomodulator use, and hematopoietic stem cell transplantation data were analyzed. Results: Of 194 patients with a diagnosis of CGD, 96 met criteria for IBD and 98 were categorized in the non-IBD group. Patients with CGD-IBD had an increased rate of infection compared with the non-IBD group (0.66 vs 0.36 infections/patient/year). Enteric organism infections were more common in patients with IBD. Immunomodulators were used at a significantly higher percentage in patients with IBD compared with patients without IBD (80% vs 56%, P < .001). Of the entire CGD cohort, 17 patients died (8.8%), with no significant difference between patients with IBD and patients without IBD (P = 1.00). Conclusion: Infectious events, enteric organism infections, and use of immunomodulatory drugs were higher in patients with IBD than patients without IBD; however, mortality was not increased. Patients with CGD and concurrent IBD are at increased risk for disease complications, supporting the importance of early recognition, diagnosis, and treatment.
MeSH term(s)	Granulomatous Disease, Chronic/diagnosis ; Granulomatous Disease, Chronic/epidemiology ; Granulomatous Disease, Chronic/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Inflammatory Bowel Diseases/epidemiology ; Inflammatory Bowel Diseases/therapy ; Registries ; Retrospective Studies
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2021.12.035
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Zs.A 7086: Show issues

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Article: Pyoderma Gangrenosum-like Wounds in Leukocyte Adhesion Deficiency: Case Report and Review of Literature.

Simpson, Andrew M / Chen, Karin / Bohnsack, John F / Lamont, Matthew N / Siddiqi, Faizi A / Gociman, Barbu

Plastic and reconstructive surgery. Global open

2018 Volume 6, Issue 8, Page(s) e1886

Abstract: Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency characterized by impairment of leukocyte migration during an inflammatory response. LAD patients can experience recurrent neutrophilic wounds similar to pyoderma gangrenosum (PG), ... ...

Abstract	Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency characterized by impairment of leukocyte migration during an inflammatory response. LAD patients can experience recurrent neutrophilic wounds similar to pyoderma gangrenosum (PG), predominantly of the skin and mucosal surfaces. There have been only a few reports addressing the management of extensive, life-threatening wounds in LAD patients. We describe here both the systemic and local management employed to successfully treat a severe PG-like cutaneous lesion in the setting of LAD in a 9-year-old female. A comprehensive literature review was performed to identify previously reported similar cases. Under aggressive systemic and local management, the wound was stabilized and complete epithelialization was achieved in 8 months. Eight studies documenting 11 patients with LAD and PG-like lesions were identified in our review of the literature. The complexity of wounds associated with LAD requires an aggressive, multidisciplinary approach. Involvement of pediatrics, immunology, plastic surgery, infectious disease, and physical therapy is essential to obtaining a positive outcome. In the setting of LAD with PG-like lesions, the only viable option is allowing for closure by secondary epithelialization. This was achieved in our patient once the wound was stabilized with the systemic administration of infliximab and topical administration of tacrolimus.
Language	English
Publishing date	2018-08-08
Publishing country	United States
Document type	Case Reports
ZDB-ID	2851682-5
ISSN	2169-7574 ; 2169-7574
ISSN (online)	2169-7574
ISSN	2169-7574
DOI	10.1097/GOX.0000000000001886
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