The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene

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Tranexamic acid-associated necrosis and intralesional thrombosis of uterine leiomyomas: A clinicopathologic study of 147 cases emphasizing the importance of drug-induced necrosis and early infarcts in leiomyomas

INTRODUCTION: Women with menorrhagia have increased levels of plasminogen activators in the endometrium. Tranexamic acid (cyklokapron), an antifibrinolytic agent, is commonly prescribed worldwide to women with menorrhagia, including those with fibroids. Necrosis in uterine leiomyomas may be associated with pregnancy, and progestogen or oral contraceptive use but its association with tranexamic acid has not been investigated. Four hundred ninety patients with uterine leiomyomas in 2004 and 2005 were reviewed. Their ages ranged from 22 to 86 (mean 47.2). One hundred forty-seven (30%) were treated with tranexamic acid. RESULTS: Infarct-type necrosis was observed in the leiomyomas of 38 patients, 22 of whom had tranexamic acid (15%) whereas the remaining 16 had no drug exposure (4.7%) (odds ratio=3.60; 95% confidence interval: 1.83-6.07; P=0.0003). Two patients who took the drug less than 2 weeks before surgery had early infarcts with appearance resembled coagulative type necrosis. Eleven of the 22 cases of drug-induced necrotic leiomyoma (50%) also showed intralesional thrombus formation, and 4 showed organization of the thrombi. CONCLUSIONS: Infarct-type necrosis and thrombosis of leiomyoma was more commonly observed in patients treated with tranexamic acid. Although the drug is effective for menorrhagia, clinicians should be aware of the possible complications associated with leiomyoma necrosis such as pain and fever. Distinguishing between types of necrosis may not always be straightforward particularly in early infarcts when the reparative connective tissue reaction between the viable and necrotic cells is not well-developed, resulting in an appearance similar to coagulative necrosis. When the overall gross and microscopic features of a leiomyoma with coagulative necrosis favor a benign lesion, the drug history should be reviewed so that this type of early and healing infarct-type necrosis is considered as the underlying cause of the apparent coagulative necrosis. This may otherwise result in a diagnosis of smooth muscle tumor of uncertain malignant potential, leading to prolonged follow-up and unnecessary further surgical intervention. © 2007 Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex

Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma

Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative realtime polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCGis one of the upstreamregulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P5 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells. © The Author 2011. Published by Oxford University Press. All rights reserved.link_to_subscribed_fulltex

FEM-based Soft Robotic Control Framework for Intracavitary Navigation

Bio-inspired robotic structure composed of soft actuation units has attracted increasing research interests in its potential and capacity of complying with unstructured and dynamic environment, as well as providing safe interaction with human; however, this inevitably poses technical challenging to achieve steady, reliable control due to the remarkable non-linearity of its kinematics and dynamics. To resolve this challenge, we propose a novel control framework that can characterize the kinematics of a soft continuum robot through the hyper-elastic Finite-element modeling (FEM). This enables frequent updates of the Jacobian mapping from the user motion input to the end-effector's point of view. Experimental validation has been conducted to show the feasibility of controlling the soft robot for intracavitary path following. This could be the first success to demonstrate the perspectives of achieving stable, accurate and effective manipulation under large change of robot morphology without having to deduce its analytical model. It is anticipated to draw further extensive attention on resolving the bottleneck against the application of FEM, namely its intensive computation

Induction and Consolidation of Calcium-Based Homo- and Heterosynaptic Potentiation and Depression.

The adaptive mechanisms of homo- and heterosynaptic plasticity play an important role in learning and memory. In order to maintain plasticity-induced changes for longer time scales (up to several days), they have to be consolidated by transferring them from a short-lasting early-phase to a long-lasting late-phase state. The underlying processes of this synaptic consolidation are already well-known for homosynaptic plasticity, however, it is not clear whether the same processes also enable the induction and consolidation of heterosynaptic plasticity. In this study, by extending a generic calcium-based plasticity model with the processes of synaptic consolidation, we show in simulations that indeed heterosynaptic plasticity can be induced and, furthermore, consolidated by the same underlying processes as for homosynaptic plasticity. Furthermore, we show that by local diffusion processes the heterosynaptic effect can be restricted to a few synapses neighboring the homosynaptically changed ones. Taken together, this generic model reproduces many experimental results of synaptic tagging and consolidation, provides several predictions for heterosynaptic induction and consolidation, and yields insights into the complex interactions between homo- and heterosynaptic plasticity over a broad variety of time (minutes to days) and spatial scales (several micrometers).Open-Access-Publikationsfonds 2016peerReviewe