68 research outputs found
Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression
Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al
The association of serum calprotectin (S100A8/S100A9) levels with disease relapses in PR3-ANCA-associated vasculitis
OBJECTIVES: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in AAV. This study investigated serum S100A8/A9 levels as a biomarker predicting future relapse in a large cohort of patients with severe ANCA-associated vasculitis (AAV). METHODS: Serum levels of S100A8/A9 were measured at baseline, months 2, and 6 following treatment initiation in 144 patients in the RAVE trial (cyclophosphamide/azathioprine vs. rituximab for induction of remission) who attained complete remission. RESULTS: Patients were divided into 4 groups: PR3-ANCA with (n=37), and without (n=56) relapse, and MPO-ANCA with (n=6) and without (n=45) relapse. Serum S100A8/A9 levels decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between relapsers and non-relapsers in the PR3-AAV group (p=0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 between baseline and month 2 (p=0.006) and baseline and month 6 (p=0.0099) for all patients. Subgroup analysis demonstrated it was patients treated with rituximab and who increased levels of S100A8/A9 who were at greatest risk of future relapse (p=0.028). CONCLUSION: An increase in serum S100A8/A9 by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with rituximab at higher risk of relapse by 18 months. As rituximab is increasingly used for remission induction in relapsing PR3-ANCA patients, S100A8/A9 may assist in identifying those patients requiring more intensive or prolonged treatment
In Vitro Cell Models for Ophthalmic Drug Development Applications
© Sara Shafaie et al. 2016; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Tissue engineering is a rapidly expanding field that aims to establish feasible techniques to fabricate biologically equivalent replacements for diseased and damaged tissues/organs. Emerging from this prospect is the development of in vitro representations of organs for drug toxicity assessment. Due to the ever-increasing interest in ocular drug delivery as a route for administration as well as the rise of new ophthalmic therapeutics, there is a demand for physiologically accurate in vitro models of the eye to assess drug delivery and safety of new ocular medicines. This review summarizes current existing ocular models and highlights the important factors and limitations that need to be considered during their use.Peer reviewe
Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression
Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma
SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine
Données ethnobotaniques et chimiques des plantes médicinales utilisées en Afrique dans les traitements traditionnels vétérinaires
Les savoirs traditionnels sur les plantes utilisées dans les traitements des personnes et des animaux en Afrique tropicale constituent une approche méthodologique de recherche industrielle de nouvelles molécules actives d’origine végétale. Une méthode basée sur des enquêtes ethnobotaniques réalisées de janvier 2010 à mai 2011 a été appliquée pour recueillir des informations sur une quarantaine de plantes réparties dans huit pays d’Afrique de l’Ouest et du Centre auprès de 181 tradipraticiens. Une recherche documentaire a été faite pour confirmer l’identité scientifique et ethnopharmacologique des plantes étudiées. Des expérimentations ont été faites pour savoir les groupes chimiques des substances actives de chacune des plantes par des essais, dosage, et réalisations au laboratoire.Les résultats trouvés présentent des groupes de plantes par propriétés thérapeutiques similaires. Les résultats prédictifs des essais cliniques demandent des recherches complémentaires d’isolement des molécules en vue de la configuration spatiale de leurs formules chimiques.Mots clés : savoirs traditionnels, plantes thérapeutiques, constituants chimiques, activités thérapeutiques, développement pharmaceutique. Afrique tropical
Effects of Surfactant Retreatment in Vitro: A Method to Evaluate Changes in Cell Junctions and in Cell Viability
The Use of Simultaneous Fluorescence and Differential Phase Confocal Microscopy to Study Alamar Blueâ„¢ Reduction in an Epithelial Cell Line
RT-PCR analysis of cardiac and skeletal muscle transcription factors, sk-fMHC, cTn-I mRNA expression.
<p><b>Lane 1</b>: ED13 ventricle, <b>Lane 2</b>: ED20 ventricle; <b>Lane 3</b>: ND0 ventricle; <b>Lane 4</b>: ND4 ventricle; <b>Lane 5</b>: PND10 ventricle; <b>Lane 6</b>: Adult ventricle; <b>Lane 7</b>: ED13 hind limbs; <b>Lane 8</b>: ED20 hind limbs, <b>Lane 9</b>: ND0 hind limbs; <b>Lane 10</b>: ND4 hind-limbs; <b>Lane 11</b>: PND10 gastrocnemius muscle; <b>Lane 12</b>: Adult gastrocnemius muscle. We note that ED20 skeletal muscle (hind limbs) mRNA expression patterns are similar to ED20 ventricular myocardium.</p
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