Search results for "fusion"
showing 10 items of 4513 documents
Preparation Steps for Measurement of Reactivity in Mouse Retinal Arterioles <em>Ex Vivo</em>
2018
Vascular insufficiency and alterations in normal retinal perfusion are among the major factors for the pathogenesis of various sight-threatening ocular diseases, such as diabetic retinopathy, hypertensive retinopathy, and possibly glaucoma. Therefore, retinal microvascular preparations are pivotal tools for physiological and pharmacological studies to delineate the underlying pathophysiological mechanisms and to design therapies for the diseases. Despite the wide use of mouse models in ophthalmic research, studies on retinal vascular reactivity are scarce in this species. A major reason for this discrepancy is the challenging isolation procedures owing to the small size of these retinal blo…
Glypican-3 and Hep Par-1 are Useful Biomarkers in the Cytologic Assessment of Ascites.
2018
Till date, the utility of cytologic assessment of ascites for the identification of hepatocellular carcinoma (HCC) cells is still debated and the usefulness of immunocytochemistry for glypican-3 (GPC3) and Hep Par-1 in this setting has not been reported. Liquid-based cytology of ascitic fluid of 28 cirrhotic patients was performed and the spots obtained were stained with hematoxylin and eosin, papanicolau, and with GPC3 and Hep Par-1 antibodies. GPC3 and Hep Par-1 antibodies stained positively the atypical cells in the ascites of 2 patients with HCC showing an exophytic growth pattern. The specimens of the patients with nonexophytic HCC, other non-HCC cancers, or cirrhosis stained negativel…
IL-4 induces the formation of multinucleated giant cells and expression of ?5 integrin in central giant cell lesion
2017
Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDN…
Imaging in mice and men: Pathophysiological insights into multiple sclerosis from conventional and advanced MRI techniques
2019
Abstract Magnetic resonance imaging (MRI) is the most important tool for diagnosing multiple sclerosis (MS). However, MRI is still unable to precisely quantify the specific pathophysiological processes that underlie imaging findings in MS. Because autopsy and biopsy samples of MS patients are rare and biased towards a chronic burnt-out end or fulminant acute early stage, the only available methods to identify human disease pathology are to apply MRI techniques in combination with subsequent histopathological examination to small animal models of MS and to transfer these insights to MS patients. This review summarizes the existing combined imaging and histopathological studies performed in M…
Defining Ewing and Ewing-like small round cell tumors (SRCT): The need for molecular techniques in their categorization and differential diagnosis. A…
2016
Abstract Background Differentiation of Ewing sarcoma family of tumors (ESFT) and Ewing-like tumors remains problematic. Certain ESFT with morphological and immunohistochemical (IHC) profiles lack the EWSR1-ETS transcript. To improve diagnostic accuracy we investigated the presence of several specific transcripts in 200 small round cell tumors (SRCT) displaying ESFT morphology and immunophenotype in which EWSR1 FISH analysis was non-informative or negative. Design 200 tumors (formalin-fixed, paraffin-embedded) were analyzed by RT-PCR. All tumors were tested for EWSR1-ETS , EWSR1 / WT1 , PAX3 / 7-FOX01 or SYT / SSX transcripts, and the negative tumors were subsequently analyzed for CIC / DUX4…
Early silent microstructural degeneration and atrophy of the thalamocortical network in multiple sclerosis
2016
Recent studies on patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) demonstrated thalamic atrophy. Here we addressed the following question: Is early thalamic atrophy in patients with CIS and relapsing-remitting MS (RRMS) mainly a direct consequence of white matter (WM) lesions-as frequently claimed-or is the atrophy stronger correlated to "silent" (nonlesional) microstructural thalamic alterations? One-hundred and ten patients with RRMS, 12 with CIS, and 30 healthy controls were admitted to 3 T magnetic resonance imaging. Fractional anisotropy (FA) was computed from diffusion tensor imaging (DTI) to assess thalamic and WM microstructure. The relative thalamic vol…
Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis
2016
Twin pregnancies are at increased risk of stillbirth. Uncomplicated twin pregnancies are commonly delivered earlier to prevent stillbirth; however, there is a risk of neonatal complications associated with being born prior to 39 weeks’ gestation. The optimal gestational age for delivery in twin pregnancies is unknown and likely varies by chorionicity. The present study aimed to determine the prospective risk of stillbirth in women with uncomplicated monochorionic and dichorionic twin pregnancies, and neonatal mortality risks, when delivered beyond 34 weeks of gestation. Data on twin pregnancies that reported rates of stillbirth were obtained from MEDLINE, EMBASE, and Cochrane Library. Separ…
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.
2019
Abstract Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <…
Small endogenous molecules as moiety to improve targeting of CNS drugs.
2016
A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…
Chimeric proteins tagged with specific 3xHA cassettes may present instability and functional problems
2017
Epitope-tagging of proteins has become a widespread technique for the analysis of protein function, protein interactions and protein localization among others. Tagging of genes by chromosomal integration of PCR amplified cassettes is a widely used and fast method to label proteins in vivo. Different systems have been developed during years in the yeast Saccharomyces cerevisiae. In the present study, we analysed systematically a set of yeast proteins that were fused to different tags. Analysis of the tagged proteins revealed an unexpected general effect on protein level when some specific tagging module was used. This was due in all cases to a destabilization of the proteins and caused a red…