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https://www.readbyqxmd.com/read/28542846/cpg-island-methylator-phenotype-identifies-high-risk-patients-among-microsatellite-stable-braf-mutated-colorectal-cancers
#1
Hege Marie Vedeld, Marianne Merok, Marine Jeanmougin, Stine A Danielsen, Hilde Honne, Gro Kummeneje Presthus, Aud Svindland, Ole H Sjo, Merete Hektoen, Mette Eknaes, Arild Nesbakken, Ragnhild A Lothe, Guro E Lind
The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni- and multivariate analyses...
May 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28539873/pharmacological-stimulation-of-phagocytosis-enhances-amyloid-plaque-clearance-evidence-from-a-transgenic-mouse-model-of-attr-neuropathy
#2
Eleni Fella, Kleitos Sokratous, Revekka Papacharalambous, Kyriacos Kyriacou, Joy Phillips, Sam Sanderson, Elena Panayiotou, Theodoros Kyriakides
Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28538758/same-tt2r2-score-in-the-outpatient-anticoagulation-clinic-to-predict-time-in-therapeutic-range-and-adverse-events
#3
Fernando Pivatto, Rafael Selbach Scheffel, Lucas Ries, Ricardo Roitman Wolkind, Roberta Marobin, Sabrina Sigal Barkan, Luís Carlos Amon, Andréia Biolo
Background: The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. Objective: To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs...
April 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28537040/accuracy-of-99mtc-hydroxymethylene-diphosphonate-scintigraphy-for-diagnosis-of-transthyretin-cardiac-amyloidosis
#4
Francesco Cappelli, Chiara Gallini, Carlo Di Mario, Egidio Natalino Costanzo, Luca Vaggelli, Francesca Tutino, Alfonso Ciaccio, Simone Bartolini, Paola Angelotti, Sabrina Frusconi, Silvia Farsetti, Giuseppe Vergaro, Assuero Giorgetti, Paolo Marzullo, Dario Genovesi, Michele Emdin, Federico Perfetto
BACKGROUND AND AIM: Either 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA. METHODS AND RESULTS: We retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA...
May 23, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28532651/suboptimal-anticoagulant-management-in-japanese-patients-with-nonvalvular-atrial-fibrillation-receiving-warfarin-for-stroke-prevention
#5
Teruyuki Hirano, Hirokazu Kaneko, Sari Mishina, Feng Wang, Satoshi Morita
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers)...
May 19, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28530526/warfarin-management-and-outcomes-in-patients-with-nonvalvular-atrial-fibrillation-within-an-integrated-health-care-system
#6
JaeJin An, Fang Niu, Chengyi Zheng, Nazia Rashid, Robert A Mendes, Diana Dills, Lien Vo, Prianka Singh, Amanda Bruno, Daniel T Lang, Paul T Le, Kristin P Jazdzewski, Gustavus Aranda
BACKGROUND: Warfarin is a common treatment option to manage patients with nonvalvular atrial fibrillation (NVAF) in clinical practice. Understanding current pharmacist-led anticoagulation clinic management patterns and associated outcomes is important for quality improvement; however, currently little evidence associating outcomes with management patterns exists. OBJECTIVES: To (a) describe warfarin management patterns and (b) evaluate associations between warfarin treatment and clinical outcomes for patients with NVAF in an integrated health care system...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28527106/a-trans-acting-factor-may-modify-age-at-onset-in-familial-amyloid-polyneuropathy-attrv30m-in-portugal
#7
Miguel Alves-Ferreira, Teresa Coelho, Diana Santos, Jorge Sequeiros, Isabel Alonso, Alda Sousa, Carolina Lemos
Although all familial amyloid polyneuropathy (FAP) ATTRV30M patients carry the same causative mutation, early (<40) and late-onset forms (≥50 years) of FAP may coexist in the same family. However, this variability in age at onset is still unexplained. To identify modifiers closely linked to the TTR locus that may in part be associated with age at onset of FAP ATTRV30M, in particular in a group of very early-onset patients (≤30 years) when compared with late-onset individuals. A clinical genetic study at a referral center comprising a sample of 910 Portuguese individuals includes 589 Val30Met carriers, 102 spouses, and 189 controls from the general population...
May 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28524240/potential-serum-biomarkers-associated-with-mild-and-severe-leptospirosis-infection-a-cohort-study-in-the-malaysian-population
#8
Tan Xue Ting, Fairuz Binti Amran, Ravindran Thayan, Norazah Ahmad, Roslinda Jaafar, Rahimah Haron, Rafidah Abdullah, Sazwan Reezal Bin Shamsuddin, Nor Suhaila Binti Md Riffin, Puteri Shafinaz Abdul-Rahman
Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild non-specific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, fifteen paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS...
May 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28516762/organophosphorus-flame-retardants-in-pregnant-women-and-their-transfer-to-chorionic-villi
#9
Fanrong Zhao, Mo Chen, Fumei Gao, Huan Shen, Jianying Hu
The potential for prenatal exposure has recently raised concerns over the health risks of endocrine disruptors; however, knowledge about human prenatal exposure to organophosphorus flame retardants (OPFRs) is lacking. In this study, 2-ethylhexyl diphenyl phosphate (EHDPP), tributyl phosphate (TBP), triphenyl phosphate (TPHP), and tris(2-chloroethyl) phosphate (TCEP) were detected in the majority of chorionic villus samples, with median concentrations of 13.6, 18.8, 11.1, and 0.51 ng/g dry weight (dw), respectively, significantly higher than those in the matching maternal decidua samples (5...
May 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28508335/toxic-potential-of-organic-constituents-of-submicron-particulate-matter-pm1-in-an-urban-road-site-barcelona
#10
Sofia R Mesquita, Barend L van Drooge, Manuel Dall'Osto, Joan O Grimalt, Carlos Barata, Natividade Vieira, Laura Guimarães, Benjamin Piña
Atmospheric particulate matter (PM) is a recognized risk factor contributing to a number of diseases in human populations and wildlife globally. Organic matter is a major component of PM, but its contribution to overall toxicity of PM has not been thoroughly evaluated yet. In the present work, the biological activity of organic extracts from PM1 (particles with less than 1 μm of aerodynamic diameter) collected from an urban road site in the centre of Barcelona (NE Spain) was evaluated using a yeast-based assay (AhR-RYA) and different gene expression markers in zebrafish embryos...
May 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28508289/somatic-mosaicism-with-reversion-to-normality-of-a-mutated-transthyretin-allele-related-to-a-familial-amyloidotic-polyneuropathy
#11
Concetta Federico, Ketty Dugo, Francesca Bruno, Anna Maria Longo, Agata Grillo, Salvatore Saccone
Familial amyloidotic polyneuropathy (FAP) is a progressive neuropathy, with onset in adulthood and high mortality. It is related to an altered transthyretin (TTR) plasma protein, mainly produced by the liver and responsible for amyloid deposit in the peripheral nervous system. SNPs in the TTR gene were associated with FAP, and the G>C substitution (NM_000371.3:c.325G>C) in the 109th codon (GAG vs CAG; NP_362.1:p.E109Q) was previously described in Sicily (Italy). Here, we report on a Sicilian family with several patients affected by FAP related to the E109Q mutation, which displayed a somatic mosaicism with the reversion to normality of the c...
May 15, 2017: Human Genetics
https://www.readbyqxmd.com/read/28501163/on-line-immunoaffinity-solid-phase-extraction-capillary-electrophoresis-mass-spectrometry-using-fab%C3%A2-antibody-fragments-for-the-analysis-of-serum-transthyretin
#12
Laura Pont, Fernando Benavente, José Barbosa, Victoria Sanz-Nebot
This paper describes an on-line immunoaffinity solid-phase extraction capillary electrophoresis mass spectrometry (IA-SPE-CE-MS) method using an immunoaffinity sorbent with Fab' antibody fragments (Fab'-IA) for the analysis of serum transthyretin (TTR), a homotetrameric protein (Mr~56,000) involved in different types of amyloidosis. The IA sorbent was prepared by covalent attachment of Fab' fragments obtained from a polyclonal IgG antibody against TTR to succinimidyl silica particles. The Fab'-IA-SPE-CE-MS methodology was first established analyzing TTR standard solutions...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28494620/genetic-testing-improves-identification-of-transthyretin-amyloid-attr-subtype-in-cardiac-amyloidosis
#13
Emily E Brown, Yi Zhen Joan Lee, Marc K Halushka, Charles Steenbergen, Nicole M Johnson, Johana Almansa, Ryan J Tedford, Oscar Cingolani, Stuart D Russell, Kavita Sharma, Daniel P Judge
Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC-MS/MS has not been evaluated...
May 11, 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28490654/early-skin-denervation-in-hereditary-and-iatrogenic-transthyretin-amyloid-neuropathy
#14
Teruaki Masuda, Mitsuharu Ueda, Genki Suenaga, Yohei Misumi, Masayoshi Tasaki, Ayane Izaki, Yukako Yanagisawa, Yasuteru Inoue, Hiroaki Motokawa, Sayaka Matsumoto, Mayumi Mizukami, Aiko Arimura, Takahisa Deguchi, Yoshihiko Nishio, Taro Yamashita, Yukihiro Inomata, Konen Obayashi, Yukio Ando
OBJECTIVE: To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis. METHODS: We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers. RESULTS: IENFD values were reduced in patients with the V30M mutation (1.9 ± 2...
May 10, 2017: Neurology
https://www.readbyqxmd.com/read/28484271/inflammatory-state-exists-in-familial-amyloid-polyneuropathy-that-may-be-triggered-by-mutated-transthyretin
#15
Genki Suenaga, Tokunori Ikeda, Teruaki Masuda, Hiroaki Motokawa, Taro Yamashita, Kotaro Takamatsu, Yohei Misumi, Mitsuharu Ueda, Hirotaka Matsui, Satoru Senju, Yukio Ando
The relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)-6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479268/progression-of-myocardial-sympathetic-denervation-assessed-by-123-i-mibg-imaging-in-familial-amyloid-polyneuropathy-and-the-effect-of-liver-transplantation
#16
Maria da Conceição Azevedo Coutinho, Nuno Cortez-Dias, Guilhermina Cantinho, Isabel Conceição, Tatiana Guimarães, Gustavo Lima da Silva, Miguel Nobre Menezes, Ana Rita Francisco, Rui Plácido, Fausto J Pinto
INTRODUCTION: Familial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR-V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine-123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR-V30M FAP...
May 4, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28479094/integrating-genotypes-in-the-same-tt2r2-score-for-the-prediction-of-anticoagulation-control-in-chinese-patients-with-atrial-fibrillation-on-warfarin
#17
Jia Liu, Nina Wang, Liuan Qin, Jun Liu, Shaozhi Xi, Xuyun Wang, Xiaoqi Li, Yuxiao Zhang, Tong Yin
INTRODUCTION: The SAMe-TT2R2 score has been proposed to predict whether patients with atrial fibrillation (AF) would be well anti-coagulated with warfarin or not. However, it might over-estimate the number of patients under suboptimal warfarin treatment in non-Caucasians. This study was designed to modify the SAMe-TT2R2 score with genotypes and validate it in Chinese AF patients treated with warfarin. MATERIAL AND METHODS: Consented Chinese-Han patients (n=510) with AF under the treatment of warfarin for at least 3months were randomly divided into a derivation (n=310) and a validation cohort (n=200)...
April 29, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28475415/transthyretin-amyloidosis-a-phenocopy-of-hypertrophic-cardiomyopathy
#18
Alexa M C Vermeer, Anneloes Janssen, Peter C Boorsma, Marcel M A M Mannens, Arthur A M Wilde, Imke Christiaans
OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder that affects over one in 500 persons worldwide. The autosomal dominant transmission of HCM implies that many relatives are at risk for HCM associated morbidity and mortality, therefore genetic testing and counselling is of great importance. However, in only 50-60% of the patients a mutation is found, which hampers predictive genetic testing in relatives. In HCM patients in whom the causal mutation has not been identified (yet), phenocopies of HCM - i...
May 5, 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28467477/waterborne-exposure-to-bps-causes-thyroid-endocrine-disruption-in-zebrafish-larvae
#19
Dan-Hua Zhang, En-Xiang Zhou, Zhu-Lin Yang
Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28460244/late-onset-cardiomyopathy-as-presenting-sign-of-attr-a45g-amyloidosis-caused-by-a-novel-ttr-mutation-p-a65g
#20
Sebastiaan H C Klaassen, Henny H Lemmink, Johan Bijzet, Andor W J M Glaudemans, Reinhard Bos, Wouter Plattel, Maarten P van den Berg, Riemer H J A Slart, Hans L A Nienhuis, Dirk J van Veldhuisen, Bouke P C Hazenberg
OBJECTIVE: The clinical description of a novel TTR gene mutation characterized by a late onset amyloid cardiomyopathy. METHODS AND RESULTS: A 78-year-old man of Dutch origin with recent surgery for bilateral carpal tunnel syndrome (CTS) was admitted to our hospital because of heart failure with preserved ejection fraction (55%). Cardiac ultrasound showed thickened biventricular walls, and cardiac magnetic resonance imaging also showed late gadolinium enhancement...
April 18, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
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