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Masaki Matsushita, Kenichi Mishima, Ryusaku Esaki, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh
OBJECTIVE Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum stenosis (FMS) is one of the serious neurological complications in ACH. Through comprehensive drug screening, the authors identified that meclozine, an over-the-counter drug for motion sickness, inhibited activation of FGFR3 signaling. Oral administration of meclozine to the growing ACH mice promoted longitudinal bone growth, but it did not prevent FMS...
October 21, 2016: Journal of Neurosurgery. Pediatrics
Sebastian Kwiatkowski, Barbara Dołęgowska, Ewa Kwiatkowska, Rafał Rzepka, Andrzej Torbè, Magdalena Bednarek-Jędrzejek
Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group...
2016: PloS One
Kristina Klaus, Susanne Fischer, Johanna M Doerr, Urs M Nater, Ricarda Mewes
PURPOSE: Fibromyalgia syndrome (FMS) is associated with psychological distress. The recent revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) raises the question of whether FMS is classifiable as "somatic symptom disorder" (SSD) and consequently as a mental disorder. To address this, the present ambulatory assessment study focuses on the everyday life occurrence of SSD symptoms in FMS and their predictive value concerning severity indicators of widespread pain...
October 18, 2016: International Journal of Behavioral Medicine
Sophie Grand'Maison, Louise Pilote, Marisa Okano, Tara Landry, Natalie Dayan
Women with prior hypertensive disorders of pregnancy (HDP) are at twice the risk of cardiovascular disease compared with women with prior normotensive pregnancy, possibly because of sustained vascular dysfunction after delivery. The aim of this systematic review and meta-analysis is to summarize evidence of vascular dysfunction at least 3 months after HDP. Articles in all languages were retrieved from principal databases. Studies included were observational, with HDP as the main exposure and measurements of vascular dysfunction via imaging modalities or serum biomarkers as the main outcome, assessed at least 3 months postpartum...
October 17, 2016: Hypertension
Telmo Pereira, Armindo Almeida, João Maldonado, Jorge Conde
OBJECTIVE: The Moens-Korteweg equation predicts changes in pulse wave velocity (PWV) following changes in arterial radius, therefore an increase in arterial radius, as seen in a reactive hyperaemia (RH) condition, should slow PWV over a given arterial segment. If this assumption is true, than the deceleration of PWV over the brachial artery (flow-mediated slowing - FMS) should be an equivalent signal of endothelial function during a conventional RH flow-mediated dilation (FMD) procedure...
September 2016: Journal of Hypertension
Tomofumi Fushima, Akiyo Sekimoto, Takahiro Minato, Takuya Ito, Yuji Oe, Kiyomi Kisu, Emiko Sato, Kenichi Funamoto, Yoshitaka Kimura, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi
OBJECTIVE: Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as soluble fms-like tyrosine kinase (sFlt-1) followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the genetics of PE has been problematic because it has been difficult to make a useful RUPP model in mice...
September 2016: Journal of Hypertension
Hironobu Nakada, Tomofumi Fushima, Akiyo Sekimoto, Yuji Oe, Emiko Sato, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi
OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria. It causes maternal death or fetal growth restriction (FGR). Although high BP can be managed with antihypertensive drugs, there is no effective treatment of FGR associated with PE. We have clarified that nicotinamide (Nam) alleviates PE-like condition and FGR induced by soluble fms-like tyrosine kinase-1 (sFlt-1) in mice. But the mechanism of how Nam works is unclear. Because Nam induces cytoprotective heme oxygenase 1 (HO-1), our aim is to clarify whether HO-1 contributes to therapeutic effect of Nam against FGR associated with PE...
September 2016: Journal of Hypertension
Emiko Sato, Yukako Tsunokuni, Tomofumi Fushima, Manami Kaneko, Ritsumi Saito, Akiyo Sekimoto, Daisuke Saigusa, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi
OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria, and is often associated with fetal growth restriction (FGR). PE is a leading cause of maternal morbidity and mortality. Although alterations in circulating angiogenic factors are pathogenic, the details of pathological mechanisms of PE remain to be elucidated. We investigated changes in metabolites in a mouse model of PE induced by overproducing soluble fms-like tyrosine kinase 1 (sFlt-1) to elucidate the pathological conditions of PE by metabolomics analysis...
September 2016: Journal of Hypertension
Volkan Solmaz, Selçuk Yavuz, Ahmet İnanr, Dürdane Aksoy, Elmas Pektaş, Aslan Tekataş, Semiha Gulsum Kurt
INTRODUCTION: our aim was to determine if there are electro diagnostic (EDX) differences between carpal tunnel syndrome (CTS) patients with diabetes mellitus (DM), CTS+hypothyroidism (HT), CTS+fibromyalgia (FMS), CTS+rheumatoid arthritis (RA), and idiopathic CTS cases by comparing nerve conduction studies (NCS). METHOD: This research examined electrophysiological studies of untreated 47 HT+CTS, 47 DM+CTS, 49 RA+CTS, 52 FMS+CTS, 50 idiopathic CTS cases, and a healthy control group of 50 individuals (total of 293 patients and 433 hands with CTS)...
October 6, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Singkome Tima, Siriporn Okonogi, Chadarat Ampasavate, Chad Pickens, Cory Berkland, Songyot Anuchapreeda
This study aimed at developing a curcumin (CM) nanoparticle targeted to Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3) protein on the surface of leukemic cells and at evaluating their properties, specificity, cytotoxicity, and inhibitory effect on FLT3 protein level in FLT3-overexpressing leukemic cells, EoL-1, and MV-4-11 cells. FLT3-specific peptides were conjugated onto modified poloxamer 407 using the copper-catalyzed azide-alkyne cycloaddition reaction. The thin film hydration method was performed for FLT3-specific CM-loaded polymeric micelles (FLT3-CM-micelles) preparation...
October 14, 2016: Journal of Pharmaceutical Sciences
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Anita Chopra, Sushant Soni, Haraprasad Pati, Dev Kumar, Rahul Diwedi, Deepak Verma, Garima Vishwakama, Sameer Bakhshi, Suman Kumar, Ajay Gogia, Rajive Kumar
BACKGROUND & OBJECTIVES: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple substitute for the standard screening molecular method...
June 2016: Indian Journal of Medical Research
Surender Kumar Sharawat, Vinod Raina, Lalit Kumar, Atul Sharma, Radhika Bakhshi, Sreenivas Vishnubhatla, Ritu Gupta, Sameer Bakhshi
BACKGROUND & OBJECTIVES: Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. METHODS: Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study...
May 2016: Indian Journal of Medical Research
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Hidenori Fujita, Akira Gomori, Yayoi Fujioka, Yuki Kataoka, Kenji Tanaka, Akihiro Hashimoto, Takamasa Suzuki, Kenjiro Ito, Tomonori Haruma, Hiromi Yamamoto-Yokoi, Naomoto Harada, Motomu Sakuragi, Nobuyuki Oda, Kenichi Matsuo, Masaki Inada, Kazuhiko Yonekura
Approximately 25-40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice...
2016: PloS One
Vivian M Gonzalez, Monica C Skewes
The firewater myth (FM) is the notion that American Indians and Alaska Natives (AI/ANs) are more susceptible to the effects of alcohol and vulnerable to alcohol problems due to biological or genetic differences. Believing that one is vulnerable to problems with alcohol may have negative effects on expectancies and drinking behavior among AI/ANs who drink; however, the association of belief in the FM with alcohol outcomes has not previously been examined. In this study we examined the factor structure of a revised version of the Firewater Myth Scale (FMS; LaMarr, 2003) and the association of belief in the FM with alcohol use, consequences, attitudes, and expectancies with 159 AI/AN college students who drink...
October 13, 2016: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
Akbar Ali, Rosemary E Gale, Abdul Rauf Shakoori
Acute myeloid leukemia (AML) is characterized by an increase in the number of myeloid cells in the marrow and an arrest in their maturation. Various genetic mutations are associated with AML. FMS-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family, plays an important role in stem cell survival, and the development of dendritic and natural killer cells. FLT3/TKD mutations are generally missense mutations or in-frame alterations of residues D835 and I836 within the activation loop of the FLT3 protein...
October 13, 2016: Journal of Cellular Biochemistry
Rui Cai, Ben D Richardson, Donald M Caspary
: Human aging studies suggest that an increased use of top-down knowledge-based resources would compensate for degraded upstream acoustic information to accurately identify important temporally rich signals. Sinusoidal amplitude-modulated (SAM) stimuli have been used to mimic the fast-changing temporal features in speech and species-specific vocalizations. Single units were recorded from auditory thalamus [medial geniculate body (MGB)] of young awake, aged awake, young anesthetized, and aged anesthetized rats...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
N Gerdes, E Farin
Objective: Taking Fibromyalgia syndrome (FMS) as an example, the article illustrates a problem that to our knowledge has not been addressed in rehabilitation research so far: According to our large dataset, a sizeable proportion of patients had to be sent home with extremely severe burdens (<2(nd) percentile in the normal population) at discharge - in spite of good improvements during their stay. Data and methods: Since 2009, patients in the RehaKlinikum Bad Säckingen, an in-patient rehab center for orthopedic-rheumatic diseases, answer the questionnaire "Indicators of Rehabilitation Status" (IRES) at the beginning and the end of their stay...
October 2016: Die Rehabilitation
Stephen S Y Lam, Eric S K Ho, Bai-Liang He, Wui-Wing Wong, Chae-Yin Cher, Nelson K L Ng, Cheuk-Him Man, Harinder Gill, Alice M S Cheung, Ho-Wan Ip, Chi-Chiu So, Jerome Tamburini, Chi Wai Eric So, Dona N Ho, Chun-Hang Au, Tsun-Leung Chan, Edmond S K Ma, Raymond Liang, Yok-Lam Kwong, Anskar Y H Leung
An in vitro drug-screening platform on patient samples was developed and validated to design personalized treatment for relapsed/refractory acute myeloid leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine (HHT), also known as omacetaxine mepesuccinate, exhibited preferential antileukemia effect against AML carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to suppress leukemia growth in vitro and in xenograft mouse models...
October 5, 2016: Science Translational Medicine
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