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Eris Tollkuci
Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
Mark W Cunningham, Javier Castillo, Tarek Ibrahim, Denise C Cornelius, Nathan Campbell, Lorena Amaral, Venkata Ramana Vaka, Nathan Usry, Jan M Williams, Babbette LaMarca
Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...
March 19, 2018: Hypertension
Hiroko Tanaka, Keiichi Kumasawa, Aiko Kakigano, Kazuya Mimura, Masayuki Endo, Takuji Tomimatsu, Tadashi Kimura
Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1...
March 13, 2018: Biochemical and Biophysical Research Communications
Clara Barneo-Caragol, Eduardo Martínez-Morillo, Susana Rodríguez-González, Paloma Lequerica-Fernández, Ignacio Vega-Naredo, Francisco V Álvarez Menéndez
BACKGROUND: Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS: The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20)...
May 2018: Journal of Trace Elements in Medicine and Biology
Charikleia Kelaidi, Antonis Kattamis, Filia Apostolakou, Christos Poziopoulos, Christina Lazaropoulou, Polyxeni Delaporta, Ino Kanavaki, Ioannis Papassotiriou
BACKGROUND: Levels of the angiogenic cytokines Placental Growth Factor (PlGF) and soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in Sickle Cell Disease and iron overload, but they have not been evaluated in Non-Transfusion-Dependent Thalassemia (NTDT). PATIENTS AND METHODS: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation and tissue hypoxia...
March 15, 2018: European Journal of Haematology
Can Chen, Xilian Huang, Kaile Wang, Kuang Chen, Danquan Gao, Shenxian Qian
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure...
April 2018: Oncology Letters
Cyril Rivat, Chamroeun Sar, Ilana Mechaly, Jean-Philippe Leyris, Lucie Diouloufet, Corinne Sonrier, Yann Philipson, Olivier Lucas, Sylvie Mallié, Antoine Jouvenel, Adrien Tassou, Henri Haton, Stéphanie Venteo, Jean-Philippe Pin, Eric Trinquet, Fabienne Charrier-Savournin, Alexandre Mezghrani, Willy Joly, Julie Mion, Martine Schmitt, Alexandre Pattyn, Frédéric Marmigère, Pierre Sokoloff, Patrick Carroll, Didier Rognan, Jean Valmier
Peripheral neuropathic pain (PNP) is a debilitating and intractable chronic disease, for which sensitization of somatosensory neurons present in dorsal root ganglia that project to the dorsal spinal cord is a key physiopathological process. Here, we show that hematopoietic cells present at the nerve injury site express the cytokine FL, the ligand of fms-like tyrosine kinase 3 receptor (FLT3). FLT3 activation by intra-sciatic nerve injection of FL is sufficient to produce pain hypersensitivity, activate PNP-associated gene expression and generate short-term and long-term sensitization of sensory neurons...
March 12, 2018: Nature Communications
Phuong L Trinh, Yen Pham
Numerous studies have identified Nucleophosmin 1 ( NPM1 ) and Fms -like tyrosine kinase 3 ( FLT3 ) as the most frequently mutated genes in Acute Myeloid Leukemia (AML) patients. Mutations occurring in these genes, including NPM1+4 (tetranucleotide insertions), FLT3-ITD (internal tandem duplications), and FLT3-TKD (tyrosine kinase domain point mutations) account for approximately 80% of all mutations found in normal karyotype AML (AML-NK) cases. Different methods have been established to detect the three listed mutations, in which, PCR-based techniques are the most widely used due to their efficiency...
January 2018: Annals of Clinical and Laboratory Science
Tianyi Qiu, Min Li, Miles A Tanner, Yan Yang, James R Sowers, Ronald J Korthuis, Michael A Hill
BACKGROUND: Accumulation of multiple subtypes of immune cells in perivascular adipose tissue (PVAT) has been proposed to cause vascular inflammation and dysfunction in type 2 diabetes (T2DM). This study was designed to investigate specific roles for dendritic cells in PVAT in the development of vascular inflammation and impaired PVAT-mediated vasorelaxation in T2DM. METHODS AND RESULTS: Studies were performed using db/db mice (model of T2DM) and their Db heterozygote (DbHET), lean and normoglycemic controls...
March 9, 2018: Metabolism: Clinical and Experimental
Siaw Li Chan, Sarosh Rana, Sireesha Chinthala, Saira Salahuddin, Kiang-Teck J Yeo
BACKGROUND: Preeclampsia is one of the leading hypertensive disorders of pregnancy. Angiogenic biomarkers such as anti-angiogenic factor soluble fms-like tyrosine kinase 1 (sFlt1) and pro-angiogenic factor placental growth factor (PlGF) are involved in the pathophysiology of preeclampsia. OBJECTIVE: The aim of this study is to validate the analytical performance of sFlt1 and PlGF on the B·R·A·H·M·S KRYPTOR Compact Plus (ThermoFisher Scientific). STUDY DESIGN: We examined K2 -EDTA plasma samples from 50 patients on B·R·A·H·M·S KRYPTOR Compact Plus, an automated immunoassay platform...
January 2018: Pregnancy Hypertension
Yvonne Kwun Yue Cheng, Lai Wa Law, Tak Yeung Leung, Oi Ka Chan, Daljit Singh Sahota
OBJECTIVE: To assess the clinical utility of the sFlt-1:PlGF ratio rule-in/rule-out pre-eclampsia either directly or after correcting each marker for gestation and maternal weight. METHODS: This was a prospective cohort study. sFlt-1, PlGF were measured in 965 women randomized to undergo a single blood withdraw between 20 and 39 weeks of gestation. sFlt-1, PlGF and the sFlt-1:PlGF ratio temporal relationship was determined. sFlt-1 and PlGF were converted to multiples of the expected gestational median (MoM) and adjusted for maternal weight...
January 2018: Pregnancy Hypertension
Myriam Stolz, Harald Zeisler, Florian Heinzl, Julia Binder, Alex Farr
OBJECTIVES: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is increased in preeclampsia. This study evaluated perinatal outcomes in cases with an sFlt-1:PlGF ratio above 655. STUDY DESIGN: We retrospectively analyzed data from all consecutive women with singleton pregnancies who presented with clinically manifest preeclampsia and underwent immediate sFlt-1:PlGF assessment. Cases with an sFlt-1:PlGF ratio ≥ 655 were matched 1:1 for gestational age to controls with a ratio < 655...
January 2018: Pregnancy Hypertension
Dorien Reijnders, Chin-Chi Liu, Xinjing Xu, Anna Zhao, Kelsey Olson, Scott D Butler, Nataki C Douglas, Jenny L Sones
Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface...
March 9, 2018: Physiological Genomics
Nan Yang, Zhenyang Gu, Zhanxiang Liu, Wenrong Huang, Shuhong Wang, Lili Wang, Chunji Gao
Multi-kinase inhibitor sorafenib showed dramatic effects in acute myeloid leukemia (AML) cells harboring fms-related tyrosine kinase 3-internal tandem duplication(FLT3-ITD) mutation. However, little is known about its therapeutic effects and underlying mechanisms on AML without this mutation. In this report, sorafenib monotherapy was utilized as a salvage treatment in two relapse/refractory AML patients without FLT3-ITD mutation. A central nervous system(CNS) relapsed patient exhibited significant shrink of tumor volume, the other patient with refractory AML, arising from chronic myelomonocytic leukemia, achieved hematological improvements...
March 7, 2018: Anti-cancer Agents in Medicinal Chemistry
Ross Armstrong, Matt Greig
OBJECTIVES: Agility is a functional requirement of many sports, challenging stability, and commonly cited as a mechanism of injury. The Functional Movement Screen (FMS) and modified Star Excursion Balance Test (mSEBT) have equivocally been associated with agility performance. The aim of the current study was to establish a hierarchical ordering of FMS and mSEBT elements in predicting T-test agility performance. DESIGN: Cross-sectional study design. SETTING: University...
January 17, 2018: Physical Therapy in Sport
S Zink, F A Moura, P Alves da Silva Autreto, D S Galvão, B Mizaikoff
Synthetic molecular recognition materials, such as molecularly imprinted polymers (MIPs), are of increasing importance in biotechnology and analytical chemistry, as they are able to selectively bind their respective template. However, due to their specificity, each MIP has to be individually designed for the desired target leading to a molecularly tailored synthesis strategy. While trial-and-error remains the common approach for selecting suitable functional monomers (FMs), the study herein introduces a radically new approach towards rationally designing MIPs by rapidly screening suitable functional monomers based on local density of states (LDOS) calculations in a technique known as Electronic Indices Methodology (EIM)...
March 8, 2018: Physical Chemistry Chemical Physics: PCCP
Liesbeth F van Vulpen, Sonja de Groot, Eugene A Rameckers, Jules G Becher, Annet J Dallmeijer
BACKGROUND: In children with cerebral palsy (CP), strength training programs to improve walking capacity and participation in activities of daily living are commonly used in clinical practice, despite lacking evidence of its effectiveness. It has been suggested that strength training with high movement velocity could be more effective than traditional resistance training to improve functional abilities such as walking. In a recently published study, we have demonstrated the positive effects of functional high-velocity resistance (power) training on muscle strength and walking capacity in young children with CP...
March 7, 2018: European Journal of Physical and Rehabilitation Medicine
Dawn S Lin, Andrey Kan, Jerry Gao, Edmund J Crampin, Philip D Hodgkin, Shalin H Naik
A thorough understanding of cellular development is incumbent on assessing the complexities of fate and kinetics of individual clones within a population. Here, we develop a system for robust periodical assessment of lineage outputs of thousands of transient clones and establishment of bona fide cellular trajectories. We appraise the development of dendritic cells (DCs) in fms-like tyrosine kinase 3 ligand culture from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures and visualize these multidimensional data using developmental interpolated t-distributed stochastic neighborhood embedding (DiSNE) time-lapse movies...
March 6, 2018: Cell Reports
Ling Cao, Sheng Wang, Prakash Venglat, Lihua Zhao, Yan Cheng, Shengjian Ye, Yuan Qin, Raju Datla, Yongming Zhou, Hong Wang
In most plants, the female germline starts with the differentiation of one megaspore mother cell (MMC) in each ovule that produces four megaspores through meiosis, one of which survives to become the functional megaspore (FM). The FM further develops into an embryo sac. Little is known regarding the control of MMC formation to one per ovule and the selective survival of the FM. The ICK/KRPs (interactor/inhibitor of cyclin-dependent kinase (CDK)/Kip-related proteins) are plant CDK inhibitors and cell cycle regulators...
March 7, 2018: PLoS Genetics
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