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Article ; Online: Sex-specific involvement of the Notch-JAG pathway in social recognition.

Jaaro-Peled, Hanna / Landek-Salgado, Melissa A / Cascella, Nicola G / Nucifora, Frederick C / Coughlin, Jennifer M / Nestadt, Gerald / Sedlak, Thomas W / Lavoie, Joelle / De Silva, Sarah / Lee, Somin / Tajinda, Katsunori / Hiyama, Hideki / Ishizuka, Koko / Yang, Kun / Sawa, Akira

Translational psychiatry

2022 Volume 12, Issue 1, Page(s) 99

Abstract: Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch-JAG pathway molecules ... ...

Abstract	Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch-JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant. Accordingly, we reverse-translated the significant finding from a surrogate tissue for neurons, and studied the behavioral profile of Notch1
MeSH term(s)	Animals ; Down-Regulation ; Female ; Humans ; Male ; Mice ; Olfactory Mucosa ; Psychotic Disorders
Language	English
Publishing date	2022-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-022-01867-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Autoimmune hypophysitis: expanding the differential diagnosis to CTLA-4 blockade.

Gutenberg, Angelika / Landek-Salgado, Melissa / Tzou, Shey-Cherng / Lupi, Isabella / Geis, Abby / Kimura, Hiroaki / Caturegli, Patrizio

Expert review of endocrinology & metabolism

2019 Volume 4, Issue 6, Page(s) 681–698

Abstract: Autoimmune hypophysitis is an increasingly recognized disorder that enters in the differential diagnosis of nonfunctioning pituitary masses. The differential diagnosis of these conditions is challenging because of similar clinical presentations and ... ...

Abstract	Autoimmune hypophysitis is an increasingly recognized disorder that enters in the differential diagnosis of nonfunctioning pituitary masses. The differential diagnosis of these conditions is challenging because of similar clinical presentations and radiological signs. This review describes the essential features of hypophysitis and the other nonfunctioning pituitary masses. It also emphasizes a recently described feature of hypophysitis: its appearance with unexpectedly high frequency in patients receiving treatments that abrogate the function of cytotoxic T lymphocyte antigen 4.
Language	English
Publishing date	2019-02-19
Publishing country	England
Document type	Journal Article
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1586/eem.09.37
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Modeling heterogeneous patients with a clinical diagnosis of schizophrenia with induced pluripotent stem cells.

Brennand, Kristen J / Landek-Salgado, Melissa A / Sawa, Akira

Biological psychiatry

2013 Volume 75, Issue 12, Page(s) 936–944

Abstract: Schizophrenia (SZ) is a devastating complex genetic mental condition that is heterogeneous in terms of clinical etiologies, symptoms, and outcomes. Despite decades of postmortem, neuroimaging, pharmacological, and genetic studies of patients, in addition ...

Abstract	Schizophrenia (SZ) is a devastating complex genetic mental condition that is heterogeneous in terms of clinical etiologies, symptoms, and outcomes. Despite decades of postmortem, neuroimaging, pharmacological, and genetic studies of patients, in addition to animal models, much of the biological mechanisms that underlie the pathology of SZ remain unknown. The ability to reprogram adult somatic cells into human induced pluripotent stem cells (hiPSCs) provides a new tool that supplies live human neurons for modeling complex genetic conditions such as SZ. The purpose of this review is to discuss the technical and clinical constraints currently limiting hiPSC-based studies. We posit that reducing the clinical heterogeneity of hiPSC-based studies, by selecting subjects with common clinical manifestations or rare genetic variants, will help our ability to draw meaningful insights from the necessarily small patient cohorts that can be studied at this time.
MeSH term(s)	Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/pathology ; Models, Neurological ; Neurons/pathology ; Schizophrenia/genetics ; Schizophrenia/pathology ; Schizophrenia/physiopathology ; Signal Transduction
Language	English
Publishing date	2013-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2013.10.025
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Article ; Online: Placenta suppresses experimental autoimmune hypophysitis through soluble TNF receptor 1.

Landek-Salgado, Melissa A / Rose, Noel R / Caturegli, Patrizio

Journal of autoimmunity

2011 Volume 38, Issue 2-3, Page(s) J88–96

Abstract: Pregnancy modulates autoimmune diseases through diverse and still incompletely defined mechanisms, in part operating at the decidua-placenta interface. To assess the immunological contribution of placenta, we administered mouse placental proteins to a ... ...

Abstract	Pregnancy modulates autoimmune diseases through diverse and still incompletely defined mechanisms, in part operating at the decidua-placenta interface. To assess the immunological contribution of placenta, we administered mouse placental proteins to a mouse model of autoimmune hypophysitis, a disease known to be strongly associated with pregnancy. Emulsified placental proteins suppressed both the cellular and humoral aspects of hypophysitis. Suppression was specific to self antigens and not seen when two foreign antigens, tetanus toxoid or tuberculin purified protein derivative, were used. Proteomic analysis revealed high levels of soluble TNF receptor 1 in placenta, suggesting that blockade of the TNF-α pathway was a mechanism of disease suppression. Placentas derived from mice deficient in TNF receptor 1 lost the ability to suppress hypophysitis. Notably, hypophysitis suppression was seen only when the TNF-α pathway was blocked locally, at the site of immunization, and not systemically. These findings provide evidence that placenta contributes to the immune tolerance of pregnancy by locally inhibiting the TNF-α pathway.
MeSH term(s)	Animals ; Autoantibodies/immunology ; Autoantigens/immunology ; Autoantigens/metabolism ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/metabolism ; Disease Models, Animal ; Female ; Immune Tolerance ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Knockout ; Pituitary Diseases/genetics ; Pituitary Diseases/immunology ; Pituitary Diseases/metabolism ; Pituitary Gland/immunology ; Placenta/immunology ; Placenta/metabolism ; Pregnancy ; Protein Binding/immunology ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; Thyroglobulin/immunology ; Thyroiditis, Autoimmune/genetics ; Thyroiditis, Autoimmune/immunology ; Thyroiditis, Autoimmune/metabolism
Chemical Substances	Autoantibodies ; Autoantigens ; Receptors, Tumor Necrosis Factor, Type I ; Thyroglobulin (9010-34-8)
Language	English
Publishing date	2011-07-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2011.07.001
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Thesis ; Online: Placental proteins, interleukin-12 and interleukin-15 influence the pathogenesis of autoimmune diseases in mice

Landek-Salgado, Melissa Anne

2010

Abstract: Autoimmune diseases affect between five and eight percent of the United States population and their pathogenesis is often unknown. Autoimmune diseases can be modulated by pregnancy in one of four ways: symptoms can improve, be unaffected, worsen, or ... ...

Abstract	Autoimmune diseases affect between five and eight percent of the United States population and their pathogenesis is often unknown. Autoimmune diseases can be modulated by pregnancy in one of four ways: symptoms can improve, be unaffected, worsen, or present in relation to pregnancy. Several theories have been proposed to explain the effect of pregnancy on autoimmunity, however, most of these theories are associated with tolerance or immunosuppression and do not account for autoimmune diseases that worsen or present in relation to pregnancy. Part one of this dissertation focuses on an autoimmune disease, autoimmune hypophysitis (AH), that presents in relation to pregnancy. The mechanisms for this association are unclear but we hypothesized that placental proteins may play a role. By using a mouse model of experimental autoimmune hypophysitis (EAH), our studies demonstrate that emulsified placental proteins uniquely suppress cell and humoral mediated autoimmune responses when co-localized with autoantigens. Conversely, non-emulsified placental proteins enhance EAH, possibly replicating syncytiotrophoblast shedding and representing a potential mechanism by which pregnancy brings about AH. We further demonstrate that placenta-derived immunoglobulin and the TNF superfamily, but not TNF-α, contribute to the suppression of EAH. Part two of this dissertation focuses on another autoimmune disease, Sjögren syndrome (SS). Although there are several mouse models of SS, none of them fully recapitulate the human disease. By using mice that over express interleukin-12, a cytokine that is elevated in SS, we show that interleukin-12 transgenic mice develop a lung and salivary phenotype similar to SS and thus represent a new model of the disease. Furthermore, we demonstrate that natural killer cells play a dual role in the pathogenesis of SS. By crossing interleukin-12 transgenic mice to interleukin-l5-/- mice, which lack natural killer cells, we show that natural killer cells induce the lung phenotype but prevent the salivary phenotype. In conclusion, our studies have enriched our understanding of the pathogenesis of AH and SS. Furthermore, our findings that placenta-derived immunoglobulin may suppress disease in a model of AH and that natural killer cells influence the initiation of disease in a model of SS could eventually lead to therapies for these diseases.
Keywords	Endocrinology\|Pathology\|Immunology
Subject code	610
Language	ENG
Publishing date	2010-01-01 00:00:01.0
Publisher	The Johns Hopkins University
Publishing country	us
Document type	Thesis ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preparation of mouse pituitary immunogen for the induction of experimental autoimmune hypophysitis.

Tzou, Shey-Cherng / Landek-Salgado, Melissa A / Kimura, Hiroaki / Caturegli, Patrizio

Journal of visualized experiments : JoVE

2010 , Issue 46

Abstract: Autoimmune hypophysitis is a chronic inflammation of the pituitary gland caused or accompanied by autoimmunity(1). It has traditionally been considered a rare disease but reporting has increased markedly in recent years. Hypophysitis, in fact, develops ... ...

Abstract	Autoimmune hypophysitis is a chronic inflammation of the pituitary gland caused or accompanied by autoimmunity(1). It has traditionally been considered a rare disease but reporting has increased markedly in recent years. Hypophysitis, in fact, develops not uncommonly as a "side effect" in cancer patients treated with antibodies that block inhibitory receptors expressed on T lymphocytes, such as CTLA-4(2) and PD-1 receptors. Autoimmune hypophysitis can be induced experimentally by injecting mice with pituitary proteins mixed with an adjuvant(3). In this video article we demonstrate how to extract proteins from mouse pituitary glands and how to prepare them in a form suitable for inducing autoimmune hypophysitis in SJL mice.
MeSH term(s)	Adjuvants, Immunologic/chemistry ; Animals ; Antigens/immunology ; Antigens/isolation & purification ; Autoimmune Diseases/immunology ; Disease Models, Animal ; Mice ; Pituitary Diseases/immunology ; Pituitary Gland/chemistry ; Pituitary Gland/immunology
Chemical Substances	Adjuvants, Immunologic ; Antigens
Language	English
Publishing date	2010-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/2181
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Induction of experimental autoimmune hypophysitis in SJL mice.

Landek-Salgado, Melissa A / Tzou, Shey-Cherng / Kimura, Hiroaki / Caturegli, Patrizio

Journal of visualized experiments : JoVE

2010 , Issue 46

Abstract: Autoimmune hypophysitis can be reproduced experimentally by the injection of pituitary proteins mixed with an adjuvant into susceptible mice(1). Mouse models allow us to study how diseases unfold, often providing a good replica of the same processes ... ...

Abstract	Autoimmune hypophysitis can be reproduced experimentally by the injection of pituitary proteins mixed with an adjuvant into susceptible mice(1). Mouse models allow us to study how diseases unfold, often providing a good replica of the same processes occurring in humans. For some autoimmune diseases, like type 1A diabetes, there are models (the NOD mouse) that spontaneously develop a disease similar to the human counterpart. For many other autoimmune diseases, however, the model needs to be induced experimentally. A common approach in this regard is to inject the mouse with a dominant antigen derived from the organ being studied. For example, investigators interested in autoimmune thyroiditis inject mice with thyroglobulin(2), and those interested in myasthenia gravis inject them with the acetylcholine receptor(3). If the autoantigen for a particular autoimmune disease is not known, investigators inject a crude protein extract from the organ targeted by the autoimmune reaction. For autoimmune hypophysitis, the pathogenic autoantigen(s) remain to be identified(4), and thus a crude pituitary protein preparation is used. In this video article we demonstrate how to induce experimental autoimmune hypophysitis in SJL mice.
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Animals ; Antigens/administration & dosage ; Antigens/immunology ; Autoimmune Diseases/immunology ; Disease Models, Animal ; Mice ; Pituitary Diseases/immunology
Chemical Substances	Adjuvants, Immunologic ; Antigens
Language	English
Publishing date	2010-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/2182
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: IgG4-related hypophysitis: a new addition to the hypophysitis spectrum.

Leporati, Paola / Landek-Salgado, Melissa A / Lupi, Isabella / Chiovato, Luca / Caturegli, Patrizio

The Journal of clinical endocrinology and metabolism

2011 Volume 96, Issue 7, Page(s) 1971–1980

Abstract: Context: Hypophysitis is a chronic inflammation of the pituitary gland that comprises an increasingly complex clinicopathological spectrum. Within this spectrum, lymphocytic and granulomatous hypophysitis are the most common forms, but newer variants ... ...

Abstract	Context: Hypophysitis is a chronic inflammation of the pituitary gland that comprises an increasingly complex clinicopathological spectrum. Within this spectrum, lymphocytic and granulomatous hypophysitis are the most common forms, but newer variants have recently been reported. Objective: The aims of the study were to describe a new patient with IgG4-related hypophysitis, review the published literature, and provide diagnostic criteria. Setting: A 75-yr-old man presented with a 1-yr history of frontal headache. Initial studies revealed panhypopituitarism and a mass in both the sella turcica and the sphenoidal sinus. The patient underwent transphenoidal surgery, initiated high-dose prednisone followed by hormone replacement therapy, and was closely monitored for 3 yr. Results: Symptoms improved after prednisone, along with shrinkage of the pituitary and sphenoidal masses, but recurred when prednisone dose was lowered. Histopathology showed a marked mononuclear infiltrate in both the pituitary and sphenoidal specimens, mainly characterized by increased numbers of plasma cells. Many of the infiltrating plasma cells (>10 per high-power field) were IgG4-positive. Review of the literature identified 11 cases of IgG4-related hypophysitis (two diagnosed based on pituitary histopathology). Conclusions: We describe the first Caucasian patient with biopsy-proven IgG4-related hypophysitis and provide classification criteria for this disease.
MeSH term(s)	Aged ; Headache/etiology ; Headache/immunology ; Headache/surgery ; Humans ; Hypophysectomy ; Immunoglobulin G/immunology ; Male ; Pituitary Diseases/complications ; Pituitary Diseases/diagnosis ; Pituitary Diseases/immunology ; Pituitary Diseases/surgery ; Pituitary Gland/immunology ; Pituitary Gland/surgery ; Treatment Outcome
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2011-05-18
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2010-2970
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Induction of experimental autoimmune hypophysitis in sjl mice

Landek-Salgado, Melissa A / Tzou, Shey-Cherng / Kimura, Hiroaki / Caturegli, Patrizio

Journal of visualized experiments. 2010 Dec. 17, , no. 46

2010

Abstract: Autoimmune hypophysitis can be reproduced experimentally by the injection of pituitary proteins mixed with an adjuvant into susceptible mice1. Mouse models allow us to study how diseases unfold, often providing a good replica of the same processes ... ...

Abstract	Autoimmune hypophysitis can be reproduced experimentally by the injection of pituitary proteins mixed with an adjuvant into susceptible mice1. Mouse models allow us to study how diseases unfold, often providing a good replica of the same processes occurring in humans. For some autoimmune diseases, like type 1A diabetes, there are models (the NOD mouse) that spontaneously develop a disease similar to the human counterpart. For many other autoimmune diseases, however, the model needs to be induced experimentally. A common approach in this regard is to inject the mouse with a dominant antigen derived from the organ being studied. For example, investigators interested in autoimmune thyroiditis inject mice with thyroglobulin2, and those interested in myasthenia gravis inject them with the acetylcholine receptor3. If the autoantigen for a particular autoimmune disease is not known, investigators inject a crude protein extract from the organ targeted by the autoimmune reaction. For autoimmune hypophysitis, the pathogenic autoantigen(s) remain to be identified4, and thus a crude pituitary protein preparation is used. In this video article we demonstrate how to induce experimental autoimmune hypophysitis in SJL mice.
Keywords	acetylcholine ; adjuvants ; animal models ; antigens ; crude protein ; diabetes ; mice ; myasthenia gravis ; proteins
Language	English
Dates of publication	2010-1217
Size	p. e2182.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/2182
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Anatabine ameliorates experimental autoimmune thyroiditis.

Caturegli, Patrizio / De Remigis, Alessandra / Ferlito, Marcella / Landek-Salgado, Melissa A / Iwama, Shintaro / Tzou, Shey-Cherng / Ladenson, Paul W

Endocrinology

2012 Volume 153, Issue 9, Page(s) 4580–4587

Abstract: Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. ... ...

Abstract	Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile.
MeSH term(s)	Alkaloids/therapeutic use ; Animals ; Cell Line ; Female ; Mice ; Pyridines/therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroiditis, Autoimmune/drug therapy
Chemical Substances	Alkaloids ; Pyridines ; anatabine (5PP654XB7D)
Language	English
Publishing date	2012-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2012-1452
Database	MEDical Literature Analysis and Retrieval System OnLINE

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