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Philip S.,St Gregorios Cardiovascular Center | Philip S.,A Unit of Frontier Lifeline | Philip S.,Animal Technology Institute | Philip S.,National Taiwan University Hospital | And 4 more authors.
Pediatrics and Neonatology

Background: Left ventricular false tendons (LVFTs) are fibrous or fibromuscular bands stretching across the left ventricle (LV) from the ventricular septum to the papillary muscle or LV free wall but not connecting, like the chordae tendinae, to the mitral leaflet. LVFTs have become the focus of studies and discussions since the advent of echocardiography. Materials and Methods: We prospectively studied the prevalence of LVFTs by two-dimensional echocardiography in 476 infants and children referred to our institute for cardiac evaluation and cardiology workup. We also studied the morphology and histopathology of LVFTs in 68 congenital heart disease specimens and in 20 piglet hearts. The literature was reviewed and the clinical significance of LVFTs was discussed. Results: LVFTs of varying size and different location were detected in 371 (77.9%) of 476 infants and children studied, in 42 (61.8%) of 68 congenital heart disease specimens, and in 19 (95.0%) of 20 piglet hearts. Of the 75 LVFTs from the congenital heart disease specimens, 33 (44.4%) were fibrous type, measuring less than 1.4 mm; 38 (50.7%) were fibromuscular type, 1.5-2.4 mm; and 4 (5.3%) were muscular type, 2.5 mm or more in diameter. Of the 33 LVFTs from the piglet hearts, 23 (69.7%) and 10 (30.3%) were fibrous and fibromuscular, respectively, and none (0.0%) was muscular. Conclusions: LVFTs were detected partially or completely by modified two-dimensional echocardiography in both normal and abnormal hearts. LVFTs is a useful anatomical landmark of LV for the differentiation of morphological LV and right ventricle in segmental analysis of congenital heart disease. LVFTs are a cause of functional murmur. No pressure gradient was noted in the mid-LV or outflow tract. LVFTs could be a contributory factor in the generation of dysrhythmias during LV catheterization studies. LVFTs were more easily identifiable in neonates and young age patients because of a better delineation of images in echocardiography. © 2011, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. Source

Chien S.-C.,National Chung Hsing University | Wu Y.-C.,Academia Sinica, Taiwan | Chen Z.-W.,Animal Technology Institute | Yang W.-C.,Academia Sinica, Taiwan | And 5 more authors.
Evidence-based Complementary and Alternative Medicine

Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes. © 2015 Shih-Chang Chien et al. Source

Philip S.,St Gregorios Cardio Vascular Center | Philip S.,Animal Technology Institute | Lee W.-C.,Animal Technology Institute | Wu M.-H.,National Taiwan University Hospital | And 2 more authors.
Pediatrics and Neonatology

Background Immune complex (IC) vasculitis can be experimentally induced in animal models by intravenous injection of horse serum (HS), and the findings of HS-induced IC vasculitis in swine were very similar to that of Kawasaki disease (KD). The IC mechanism may be involved in the pathogenesis of vasculitis in KD. Here, we studied the two-dimensional (2D) echocardiographic and histopathological findings of acute, subacute, and healing phases of vasculitis induced by two different types of HS, and the reproducibility of IC vasculitis in swine. Methods and results Our study group consisted of 24 pure-bred landrace male piglets of 1.5-3 months of age. They were divided into three HS groups (n = 17), namely, Group A (n = 8) receiving gamma globulin-free HS, and Group B (n = 6) receiving donor herd HS, three doses at 5-day intervals, and Group C (n = 3) that received only one dose of donor herd HS on Day 1, and the saline group (n = 7) that received three doses of intravenous normal saline (NS) at 5-day intervals. The 2D echocardiography was performed every 3-4 days, and all piglets were killed for histopathological studies at different dates from Days 2 to Day 60. All the HS groups developed rashes and demonstrated significant dilation (54-150%) of coronary arteries in Groups A and B; when compared (p < 0.02) with 9-53% dilation in Group C and the saline group. Histopathological changes of test groups were asymmetric coronary vasculitis in various stages, whereas none of the piglets in the control group developed vasculitis. No significant difference in the echocardiographic and histopathological findings was observed among the piglets that received two types of HS. Conclusion HS can induce IC vasculitis in swine. The rashes and 2D echocardiographic and histopathological studies of the acute to healing phases showed close similarities with KD, and it is concluded that swine may serve as a unique experimental model for IC vasculitis and for various therapeutic trials. © 2014, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. Source

Lee K.-H.,Animal Technology Institute | Chuang C.-K.,Animal Technology Institute | Guo S.-F.,Animal Technology Institute | Tu C.-F.,Animal Technology Institute
Stem Cells and Development

The inhibition of endogenous differentiation-inducing signaling or the enhancement of growth capacity and viability of preimplantation embryos, via 2i (PD0325901 and CHIR99021), dramatically improves the establishment of mouse embryonic stem cells (mESCs). Using adrenocorticotropic hormone fragments 1-24 (ACTH 1-24), which enhances survival and/or proliferation of mESCs, also increases the derivation of mESCs from single blastomeres significantly. The CHIR99021 pathway and the proposed ACTH pathway are likely different. Therefore, this study aimed to assess the synergetic effects of 2i and ACTH 1-24 on derivation of mESCs. Results in the present study demonstrate that germline-transmitted mESCs could be efficiently derived from ICR and C57BL/6J at 0.5-4.5 days postcoitum denuded zygotes to blastocysts or isolated blastomeres of 2-8-cell embryos and cultured in 10μL droplets with human foreskin fibroblast (Hs68) or STO (a mouse embryonic fibroblast line) feeders and in knockout serum replacement (KSR) ESC medium containing 2i or ACTH 1-24. The overall success rates for C57BL/6J and ICR were 56.2% when cultured in 2i+ACTH 1-24, 26.6% in 2i, 6.7% in ACTH 1-24, and 4.8% in KSR ESC medium. These results imply that CHIR99021 and ACTH 1-24 are synergistically enhancing the establishment of mESCs. The proposed protocol also demonstrates a highly efficient and reproducible method, has a simple layout, is easy to apply, and could be used as an alternative method for routinely establishing mESC lines. © Copyright 2012, Mary Ann Liebert, Inc. 2012. Source

Chang J.-T.,Animal Technology Institute | Chen Y.-C.,Animal Technology Institute | Chou Y.-C.,Animal Technology Institute | Wang S.-R.,Animal Technology Institute

All biological products are derived from complex living systems and are often mixed with large numbers of impurities. For reasons of safety, residual host-cell DNA must be eliminated during processing. To assay host-cell DNA content in biopharmaceutical products derived from porcine sources, this study applies the quantitative real-time polymerase chain reaction (Q-PCR) method. The optimized assay in this study is based on the pol region of the porcine endogenous retrovirus (PERV). Assay validation results demonstrate that the proposed assay has appropriate accuracy, preciseness, reproducibility, and sensitivity. Primer and probe specificity are evaluated in real-time Q-PCR reactions using genomic DNA from rabbit, mouse, cat, hamster, monkey, human cell, yeast, and Escherichia coli as templates. The sensitivity of real-time Q-PCR is determined using genomic DNA from the porcine kidney cell line. The reliable detection range is within 0.5-105pg/reaction. The limit of quantitation is 500fg. The sensitivity of the assay meets the authority criterion. Moreover, the assay is applied to determine the level of host-cell DNA in recombinant human coagulation factor IX (rhFIX) from transgenic pigs. The real-time Q-PCR assay is thus a promising new tool for quantitative detection and clearance validation of residual porcine DNA when manufacturing recombinant therapeutics. © 2013. Source

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