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Milena furtado

Milena B Furtado, Muneer Hasham
This chapter will discuss the role of cardiac fibroblasts as a target of various immunological inputs as well as an immunomodulatory hub of the heart through interaction with immune cell types and chemokine or cytokine signaling. While the purpose of this chapter is to explore the immunomodulatory properties of cardiac fibroblasts, it is important to note that cardiac fibroblasts are not a homogeneous cell type, but have a unique embryological origin and molecular identity. Specific properties of cardiac fibroblasts may influence the way they interact with the heart microenvironment to promote healthy homeostatic function or respond to pathological insults...
2017: Advances in Experimental Medicine and Biology
Hieu T Nim, Milena B Furtado, Mirana Ramialison, Sarah E Boyd
BACKGROUND: Quantitative high-throughput data deposited in consortia such as International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) present opportunities and challenges for computational analyses. METHODS: We present a computational strategy to systematically rank and investigate a large number (2(10)-2(20)) of clinically testable gene sets, using combinatorial gene subset generation and disease-free survival (DFS) analyses. This approach integrates protein-protein interaction networks, gene expression, DNA methylation, and copy number data, in association with DFS profiles from patient clinical records...
2017: Frontiers in Oncology
Milena B Furtado, Julia C Wilmanns, Anjana Chandran, Joelle Perera, Olivia Hon, Christine Biben, Taylor J Willow, Hieu T Nim, Gurpreet Kaur, Stephanie Simonds, Qizhu Wu, David Willians, Ekaterina Salimova, Nicolas Plachta, James M Denegre, Stephen A Murray, Diane Fatkin, Michael Cowley, James T Pearson, David Kaye, Mirana Ramialison, Richard P Harvey, Nadia A Rosenthal, Mauro W Costa
Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease-generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5-driven pathology, a primary right ventricular dysfunction...
March 23, 2017: JCI Insight
Asaf Ta-Shma, Kai Zhang, Ekaterina Salimova, Alma Zernecke, Daniel Sieiro-Mosti, David Stegner, Milena Furtado, Avraham Shaag, Zeev Perles, Bernhard Nieswandt, Azaria J J T Rein, Nadia Rosenthal, Aaron M Neiman, Orly Elpeleg
BACKGROUND: The underlying molecular aetiology of congenital heart defects is largely unknown. The aim of this study was to explore the genetic basis of non-syndromic severe congenital valve malformations in two unrelated families. METHODS: Whole-exome analysis was used to identify the mutations in five patients who suffered from severe valvular malformations involving the pulmonic, tricuspid and mitral valves. The significance of the findings was assessed by studying sporulation of yeast carrying a homologous Phospholipase D (PLD1) mutation, in situ hybridisation in chick embryo and echocardiography and histological examination of hearts of PLD1 knockout mice...
April 2017: Journal of Medical Genetics
Milena B Furtado
No abstract text is available yet for this article.
September 2016: Differentiation; Research in Biological Diversity
Thiruma V Arumugam, Silvia Manzanero, Milena Furtado, Patrick J Biggins, Yu-Hsuan Hsieh, Mathias Gelderblom, Kelli Pa MacDonald, Ekaterina Salimova, Yu-I Li, Othmar Korn, Deborah Dewar, I Mhairi Macrae, Robert B Ashman, Sung-Chun Tang, Nadia A Rosenthal, Marc J Ruitenberg, Tim Magnus, Christine A Wells
The C-type lectin Mincle is implicated in innate immune responses to sterile inflammation, but its contribution to associated pathologies is not well understood. Herein, we show that Mincle exacerbates neuronal loss following ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a model of transient middle cerebral artery occlusion but did not alter outcomes following heart or gut ischemia. High functional scores in Mincle KO animals using the focal cerebral ischemia model were accompanied by reduced lesion size, fewer infiltrating leukocytes and less neutrophil-derived cytokine production than isogenic controls...
June 2017: Journal of Cerebral Blood Flow and Metabolism
Milena B Furtado, Mauro W Costa, Nadia A Rosenthal
The mammalian heart is responsible for supplying blood to two separate circulation circuits in a parallel manner. This design provides efficient oxygenation and nutrients to the whole body through the left-sided pump, while the right-sided pump delivers blood to the pulmonary circulation for re-oxygenation. In order to achieve this demanding job, the mammalian heart evolved into a highly specialised organ comprised of working contractile cells or cardiomyocytes, a directional and insulated conduction system, capable of independently generating and conducting electric impulses that synchronises chamber contraction, valves that allow the generation of high pressure and directional blood flow into the circulation, coronary circulation, that supplies oxygenated blood for the heart muscle high metabolically active pumping role and inlet/outlet routes, as the venae cavae and pulmonary veins, aorta and pulmonary trunk...
September 2016: Differentiation; Research in Biological Diversity
Joanna d'Arc Lyra Batista, Mariana Vargas Furtado, Natan Katz, Milena Rodrigues Agostinho, Brasil Silva Neto, Erno Harzheim, Carisi Anne Polanczyk
BACKGROUND: Many Brazilian patients with complex diseases who are treated in tertiary referral clinics have been stable for long periods. The main needs of these patients involve monitoring of risk factors and review of drug prescriptions, which could be satisfactorily done in primary care facilities. The goal of this protocol is to evaluate the safety and effectiveness of telemedicine services to support the transition of patients with stable chronic coronary artery disease from the tertiary to the primary level of care...
July 7, 2016: BMC Health Services Research
Milena B Furtado, Julia C Wilmanns, Anjana Chandran, Mary Tonta, Christine Biben, Michael Eichenlaub, Harold A Coleman, Silke Berger, Romaric Bouveret, Reena Singh, Richard P Harvey, Mirana Ramialison, James T Pearson, Helena C Parkington, Nadia A Rosenthal, Mauro W Costa
Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy...
January 2016: Differentiation; Research in Biological Diversity
Milena B Furtado, Hieu T Nim, Sarah E Boyd, Nadia A Rosenthal
In the adult, tissue repair after injury is generally compromised by fibrosis, which maintains tissue integrity with scar formation but does not restore normal architecture and function. The process of regeneration is necessary to replace the scar and rebuild normal functioning tissue. Here, we address this problem in the context of heart disease, and discuss the origins and characteristics of cardiac fibroblasts, as well as the crucial role that they play in cardiac development and disease. We discuss the dual nature of cardiac fibroblasts, which can lead to scarring, pathological remodelling and functional deficit, but can also promote heart function in some contexts...
February 1, 2016: Development
Milena B Furtado, Hieu T Nim, Jodee A Gould, Mauro W Costa, Nadia A Rosenthal, Sarah E Boyd
Heart failure is one of the leading causes of death worldwide [1-4]. Current therapeutic strategies are inefficient and cannot cure this chronic and debilitating condition [5]. Ultimately, heart transplants are required for patient survival, but donor organs are scarce in availability and only prolong the life-span of patients for a limited time. Fibrosis is one of the main pathological features of heart failure [6,7], caused by inappropriate stimulation of fibroblasts and excessive extracellular matrix production...
December 2014: Genomics Data
Hieu T Nim, Milena B Furtado, Mauro W Costa, Nadia A Rosenthal, Hiroaki Kitano, Sarah E Boyd
BACKGROUND: Existing de novo software platforms have largely overlooked a valuable resource, the expertise of the intended biologist users. Typical data representations such as long gene lists, or highly dense and overlapping transcription factor networks often hinder biologists from relating these results to their expertise. RESULTS: VISIONET, a streamlined visualisation tool built from experimental needs, enables biologists to transform large and dense overlapping transcription factor networks into sparse human-readable graphs via numerically filtering...
2015: BMC Bioinformatics
Bert Gold, Milena Cankovic, Larissa V Furtado, Frederick Meier, Christopher D Gocke
Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring...
May 2015: Journal of Molecular Diagnostics: JMD
Bert Gold, Milena Cankovic, Larissa V Furtado, Frederick Meier, Christopher D Gocke
Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring...
April 8, 2015: Journal of Molecular Diagnostics: JMD
Marcus Vinícius Pinheiro Mendonça, Ticiana Ferreira Larocca, Bruno Solano de Freitas Souza, Cristiane Flora Villarreal, Luiz Flávio Maia Silva, André Costa Matos, Marco Antonio Novaes, Cláudia Maria Pinheiro Bahia, Ana Carine de Oliveira Melo Martinez, Carla Martins Kaneto, Sissi Brandão Carneiro Furtado, Geraldo Pedral Sampaio, Milena Botelho Pereira Soares, Ricardo Ribeiro dos Santos
INTRODUCTION: The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI...
November 17, 2014: Stem Cell Research & Therapy
Erika Lira de Oliveira, Fabiana Furtado Freitas, Cristina Gomes de Macedo, Juliana Trindade Clemente-Napimoga, Milena Bortolotto Felippe Silva, Luiz Roberto Coutinho Manhães-Jr, José Luiz Cintra Junqueira, Marcelo Henrique Napimoga
OBJECTIVE: Low dose propranolol has previously been demonstrated to suppress bone remodelling. Therefore, its effect on orthodontic movement was tested. DESIGN: Rats were assigned as follows (n=5): animals with no orthodontic appliance (G1); the remaining groups were fitted with a Ni-Ti closed-coil spring ligated to the upper left first molar and connected to the incisors using metal and resin and received vehicle only (G2), 0.1mg/kg (G3) or 20mg/kg (G4) of propranolol orally...
October 2014: Archives of Oral Biology
Milena B Furtado, Mauro W Costa, Edward A Pranoto, Ekaterina Salimova, Alexander R Pinto, Nicholas T Lam, Anthony Park, Paige Snider, Anjana Chandran, Richard P Harvey, Richard Boyd, Simon J Conway, James Pearson, David M Kaye, Nadia A Rosenthal
RATIONALE: Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment, but appreciation of their contribution has suffered from incomplete characterization and lack of cell-specific markers. OBJECTIVE: To generate an unbiased comparative gene expression profile of the cardiac fibroblast pool, identify and characterize the role of key genes in cardiac fibroblast function, and determine their contribution to myocardial development and regeneration...
April 25, 2014: Circulation Research
Tanya L Medley, Milena Furtado, Nicholas T Lam, Rejhan Idrizi, David Williams, Paul J Verma, Mauro Costa, David M Kaye
BACKGROUND: Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes. OBJECTIVE: We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process...
2013: PloS One
Mauro W Costa, Guanglan Guo, Orit Wolstein, Molly Vale, Maria L Castro, Libin Wang, Robyn Otway, Peter Riek, Natalie Cochrane, Milena Furtado, Christopher Semsarian, Robert G Weintraub, Thomas Yeoh, Christopher Hayward, Anne Keogh, Peter Macdonald, Michael Feneley, Robert M Graham, Jonathan G Seidman, Christine E Seidman, Nadia Rosenthal, Diane Fatkin, Richard P Harvey
BACKGROUND: The transcription factor NKX2-5 is crucial for heart development, and mutations in this gene have been implicated in diverse congenital heart diseases and conduction defects in mouse models and humans. Whether NKX2-5 mutations have a role in adult-onset heart disease is unknown. METHODS AND RESULTS: Mutation screening was performed in 220 probands with adult-onset dilated cardiomyopathy. Six NKX2-5 coding sequence variants were identified, including 3 nonsynonymous variants...
June 2013: Circulation. Cardiovascular Genetics
Paulo Sampaio Furtado, Milena Paiva Costa, Flávia Ribeiro do Prado Valladares, Leandro Oliveira da Silva, Maurício Lordêlo, Isa Lyra, Ubirajara Barroso
To evaluate priapism rates in individuals <18 years of age with sickle cell disease (SCD) at a referral center. An evaluation was made of 599 consecutive male patients with SCD, separated according to type of hemoglobinopathy (HbSS, HbSC and HbS-β-thalassemia). Age at first episode and number of episodes were recorded. Cases of sickle cell trait were excluded. Mean age was similar in all groups. Overall, priapism occurred in 3.6 % of patients (5.6 % of those with HbSS and 1.1 % of those with HbSC; P = 0...
June 2012: International Journal of Hematology
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