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  • 1
    Online Resource
    Online Resource
    Toward improved myocardial maturity in an organ-on-chip platform with immature cardiac myocytes
    SAGE Publications ; 2017
    In:  Experimental Biology and Medicine Vol. 242, No. 17 ( 2017-11), p. 1643-1656
    Details
    In: Experimental Biology and Medicine, SAGE Publications, Vol. 242, No. 17 ( 2017-11), p. 1643-1656
    Abstract: In vitro studies of cardiac physiology and drug response have traditionally been performed on individual isolated cardiomyocytes or isotropic monolayers of cells that may not mimic desired physiological traits of the laminar adult myocardium. Recent studies have reported a number of advances to Heart-on-a-Chip platforms for the fabrication of more sophisticated engineered myocardium, but cardiomyocyte immaturity remains a challenge. In the anisotropic musculature of the heart, interactions between cardiac myocytes, the extracellular matrix (ECM), and neighboring cells give rise to changes in cell shape and tissue architecture that have been implicated in both development and disease. We hypothesized that engineered myocardium fabricated from cardiac myocytes cultured in vitro could mimic the physiological characteristics and gene expression profile of adult heart muscle. To test this hypothesis, we fabricated engineered myocardium comprised of neonatal rat ventricular myocytes with laminar architectures reminiscent of that observed in the mature heart and compared their sarcomere organization, contractile performance characteristics, and cardiac gene expression profile to that of isolated adult rat ventricular muscle strips. We found that anisotropic engineered myocardium demonstrated a similar degree of global sarcomere alignment, contractile stress output, and inotropic concentration–response to the β-adrenergic agonist isoproterenol. Moreover, the anisotropic engineered myocardium exhibited comparable myofibril related gene expression to muscle strips isolated from adult rat ventricular tissue. These results suggest that tissue architecture serves an important developmental cue for building in vitro model systems of the myocardium that could potentially recapitulate the physiological characteristics of the adult heart. Impact statement With the recent focus on developing in vitro Organ-on-Chip platforms that recapitulate tissue and organ-level physiology using immature cells derived from stem cell sources, there is a strong need to assess the ability of these engineered tissues to adopt a mature phenotype. In the present study, we compared and contrasted engineered tissues fabricated from neonatal rat ventricular myocytes in a Heart-on-a-Chip platform to ventricular muscle strips isolated from adult rats. The results of this study support the notion that engineered tissues fabricated from immature cells have the potential to mimic mature tissues in an Organ-on-Chip platform.
    Type of Medium: Online Resource
    ISSN: 1535-3702 , 1535-3699
    URL: Article
    DOI: 10.1177/1535370217701006
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2020856-X
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  • 2
    Online Resource
    Online Resource
    Drug-induced Liver Fibrosis : Testing Nevirapine in a Viral-like Liver Setting Using Histopathology, MALDI IMS, and Gene Expression
    SAGE Publications ; 2016
    In:  Toxicologic Pathology Vol. 44, No. 1 ( 2016-01), p. 112-131
    Details
    In: Toxicologic Pathology, SAGE Publications, Vol. 44, No. 1 ( 2016-01), p. 112-131
    Abstract: Nevirapine (NVP) is associated with hepatotoxicity in 1–5% of patients. In rodent studies, NVP has been shown to cause hepatic enzyme induction, centrilobular hypertrophy, and skin rash in various rat strains but not liver toxicity. In an effort to understand whether NVP is metabolized differently in a transiently inflamed liver and whether a heightened immune response alters NVP-induced hepatic responses, female brown Norway rats were dosed with either vehicle or NVP alone (75 mg/kg/day for 15 days) or galactosamine alone (single intraperitoneal [ip] injection on day 7 to mimic viral hepatitis) or a combination of NVP (75/100/150 mg/kg/day for 15 days) and galactosamine (single 750 mg/kg ip on day 7). Livers were collected at necropsy for histopathology, matrix-assisted laser desorption/ionization imaging mass spectrometry and gene expression. Eight days after galactosamine, hepatic fibrosis was noted in rats dosed with the combination of NVP and galactosamine. No fibrosis occurred with NVP alone or galactosamine alone. Gene expression data suggested a viral-like response initiated by galactosamine via RNA sensors leading to apoptosis, toll-like receptor, and dendritic cell responses. These were exacerbated by NVP-induced growth factor, retinol, apoptosis, and periostin effects. This finding supports clinical reports warning against exacerbation of fibrosis by NVP in patients with hepatitis C.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    URL: Article
    DOI: 10.1177/0192623315617033
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2056753-4
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  • 3
    Online Resource
    Online Resource
    Apo-Metallothionein Emerging as a Major Player in the Cellular Activities of Metallothionein
    SAGE Publications ; 2006
    In:  Experimental Biology and Medicine Vol. 231, No. 9 ( 2006-10), p. 1528-1534
    Details
    In: Experimental Biology and Medicine, SAGE Publications, Vol. 231, No. 9 ( 2006-10), p. 1528-1534
    Abstract: Observations of apo-metallothlonein (apo-MT) have been made under a variety of physiologic circumstances, including zinc deficiency in cell culture and in rodents, cellular induction of MT by dexamethasone with concurrent Zn deficiency, a variety of tumors under normal Zn conditions, MT induction by Zn and Bi citrate, induction of hepatic MT after tumor cell Injection into nude mice, and overexpression of cardiac MT in MT transgenic mice. Experiments demonstrating both the lability of Zn and Cu bound to MT and the cellular stability of apo-MT are described to help rationalize the widespread presence of this metal-depleted species. Finally, comparative in vitro and cellular experiments examined the relative reactivity of Zn- and apo-MT with nitric oxide species, showing that apo-MT is much more reactive chemically and that in cells it may be a principal reactive species within the MT pool.
    Type of Medium: Online Resource
    ISSN: 1535-3702 , 1535-3699
    URL: Article
    DOI: 10.1177/153537020623100912
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 2020856-X
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  • 4
    Online Resource
    Online Resource
    Multilevel Mediation Modeling in Group-Based Intervention Studies
    SAGE Publications ; 1999
    In:  Evaluation Review Vol. 23, No. 4 ( 1999-08), p. 418-444
    Details
    In: Evaluation Review, SAGE Publications, Vol. 23, No. 4 ( 1999-08), p. 418-444
    Abstract: This article proposes and evaluates a method to test for mediation in multilevel data sets formed when an intervention administered to intact groups is designed to produce change in individual mediator and outcome variables. Simulated data of this form were used to compare ordinary least squares (OLS) and two multilevel estimators of the mediated effect. OLS and multilevel standard error approximations were also evaluated and recommendations given for optimal estimator choice. These methods were applied to data from an existing substance use intervention to show the impact multilevel mediation modeling can have on the conclusions drawn from real-world evaluation studies.
    Type of Medium: Online Resource
    ISSN: 0193-841X , 1552-3926
    URL: Article
    DOI: 10.1177/0193841X9902300404
    RVK:
    CL 1000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1999
    detail.hit.zdb_id: 1500138-6
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  • 5
    Online Resource
    Online Resource
    Applications of Laser Scanning Cytometry in Immunohistochemistry and Routine Histopathology
    SAGE Publications ; 2008
    In:  Toxicologic Pathology Vol. 36, No. 1 ( 2008-01), p. 117-132
    Details
    In: Toxicologic Pathology, SAGE Publications, Vol. 36, No. 1 ( 2008-01), p. 117-132
    Abstract: Laser scanning cytometry (LSC) is a powerful tool for qualitative and quantitative analysis of tissue sections in preclinical drug development. LSC combines the strengths of flow cytometry with tissue architecture retention. This technology has been used predominantly with immunofluorescent techniques on cell culture and tissue sections, but recently LSC has shown promise in evaluating chromogenic immunohistochemistry (IHC) and histochemical products in paraffin-embedded and/or frozen tissue sections. Inverted light scatter measurements or a combination of inverted scatter and fluorescence allows automated determination of cell/nuclear counts (e.g., proliferation labeling indices), cell area (e.g., cellular hypertrophy), stromal elements, and labeling intensity (e.g., cytoplasmic/organellar proteins) in chromogen-labeled IHC or histochemical stained sections that correlates well with standard manual quantification methods. Segmentation with autofluorescence or dual immunolabeling facilitates capture of labeling data from specific cell populations. LSC evaluation of HE-stained sections is accomplished using autofluorescence/eosin fluorescence and inverse scatter. A standardized fluorescent approach with archivability, a lack of fluorescence quenching (photobleaching), and amenability to evaluation of multiple markers in a section has been demonstrated using Qdot® nanocrystals. Examples of LSC use in chromogenic IHC, routine histopathology, and Qdot® labeling will be reviewed, and advantages and disadvantages of this technology will be discussed.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    URL: Article
    DOI: 10.1177/0192623307312704
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 2056753-4
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  • 6
    Online Resource
    Online Resource
    A Poorly Differentiated Germ Cell Tumor (Seminoma) in a Long Evans Rat
    SAGE Publications ; 1998
    In:  Toxicologic Pathology Vol. 26, No. 5 ( 1998-09), p. 691-694
    Details
    In: Toxicologic Pathology, SAGE Publications, Vol. 26, No. 5 ( 1998-09), p. 691-694
    Abstract: A large neoplasm that replaced 1 testis of a Long Evans Rat was noted at the final necropsy of a dietary 2-yr study. By light microscopy, the morphological features were consistent with a poorly differentiated seminoma. Ultrastructurally, the cells were polygonal, had a round nucleus, had straight cellular boundaries, and bore no resemblance to Sertoli cells. Although there was little evidence of spermatocytic differentiation, the presence of proacrosomal granules and vesicles, prominent Golgi apparatus, tight intercellular junctions, and a few centriolar pairs without axoneme development, in conjunction with the absence of lipid droplets or abundant smooth endoplasmic reticulum, supported the diagnosis of seminoma rather than Leydig cell tumor. The cells were S-100-and vimentin-positive, although cytokeratin- and a-fetoprotein-negative. Seminomas are extremely rare neoplasms in rats; this is the first report in this strain and the first extensive analysis of a rat seminoma without spermatocytic differentiation.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    URL: Article
    DOI: 10.1177/019262339802600515
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1998
    detail.hit.zdb_id: 2056753-4
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