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Al amyloid

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https://www.readbyqxmd.com/read/29153741/left-atrial-function-in-patients-with-light-chain-amyloidosis-a-transthoracic-3d-speckle-tracking-imaging-study
#1
Dania Mohty, Vincent Petitalot, Julien Magne, Bahaa M Fadel, Cyrille Boulogne, Dounia Rouabhia, Chahrazed ElHamel, David Lavergne, Thibaud Damy, Victor Aboyans, Arnaud Jaccard
BACKGROUND: Systemic light chain amyloidosis (AL) is characterized by the extracellular deposition of amyloid fibrils. Transthoracic echocardiography is the modality of choice to assess cardiac function in patients with AL. Whereas left ventricular (LV) function has been well studied in this patient population, data regarding the value of left atrial (LA) function in AL patients are lacking. In this study, we aim to examine the impact of LA volumes and function on survival in AL patients as assessed by real-time 3D echocardiography...
November 16, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29147557/the-diversity-and-utility-of-amyloid-fibrils-formed-by-short-amyloidogenic-peptides
#2
REVIEW
Zahraa S Al-Garawi, Kyle L Morris, Karen E Marshall, Jutta Eichler, Louise C Serpell
Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-β amyloid architecture. Many amino acid sequences are able to self-assemble to form amyloid with a cross-β core. Here we describe our recent advances in understanding how sequence contributes to amyloidogenicity and structure...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29142197/proteotoxicity-in-cardiac-amyloidosis-amyloidogenic-light-chains-affect-the-levels-of-intracellular-proteins-in-human-heart-cells
#3
Esther Imperlini, Massimiliano Gnecchi, Paola Rognoni, Eduard Sabidò, Maria Chiara Ciuffreda, Giovanni Palladini, Guadalupe Espadas, Francesco Mattia Mancuso, Margherita Bozzola, Giuseppe Malpasso, Veronica Valentini, Giuseppina Palladini, Stefania Orrù, Giovanni Ferraro, Paolo Milani, Stefano Perlini, Francesco Salvatore, Giampaolo Merlini, Francesca Lavatelli
AL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposed in vitro to soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141588/parkinson-disease-polygenic-risk-score-is-associated-with-parkinson-disease-status-and-age-at-onset-but-not-with-alpha-synuclein-cerebrospinal-fluid-levels
#4
Laura Ibanez, Umber Dube, Benjamin Saef, John Budde, Kathleen Black, Alexandra Medvedeva, Jorge L Del-Aguila, Albert A Davis, Joel S Perlmutter, Oscar Harari, Bruno A Benitez, Carlos Cruchaga
BACKGROUND: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau)...
November 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29134678/systemic-immune-checkpoint-blockade-with-anti-pd1-antibodies-does-not-alter-cerebral-amyloid-%C3%AE-burden-in-several-amyloid-transgenic-mouse-models
#5
Martine Latta-Mahieu, Bradford Elmer, Alexis Bretteville, Yaming Wang, Mati Lopez-Grancha, Philippe Goniot, Nicolas Moindrot, Paul Ferrari, Véronique Blanc, Nathalie Schussler, Emmanuel Brault, Valérie Roudières, Véronique Blanchard, Zhi-Yong Yang, Pascal Barneoud, Philippe Bertrand, Bart Roucourt, Sofie Carmans, Astrid Bottelbergs, Liesbeth Mertens, Cindy Wintmolders, Peter Larsen, Caroline Hersley, Tyler McGathey, Margaret M Racke, Ling Liu, Jirong Lu, Michael J O'Neill, David R Riddell, Andreas Ebneth, Gary J Nabel, Laurent Pradier
Chronic inflammation represents a central component in the pathogenesis of Alzheimer's disease (AD). Recent work suggests that breaking immune tolerance by Programmed cell Death-1 (PD1) checkpoint inhibition produces an IFN-γ-dependent systemic immune response, with infiltration of the brain by peripheral myeloid cells and neuropathological as well as functional improvements even in mice with advanced amyloid pathology (Baruch et al., (): Nature Medicine, 22:135-137). Immune checkpoint inhibition was therefore suggested as potential treatment for neurodegenerative disorders when activation of the immune system is appropriate...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29133141/abdominal-fat-pad-excisional-biopsy-for-the-diagnosis-and-typing-of-systemic-amyloidosis
#6
Yessica Garcia, A Bernard Collins, James R Stone
In the past, the diagnosis and typing of amyloidosis often required an invasive biopsy of an internal organ, such as the heart or kidneys. Abdominal fat pad excisional biopsy (FPEB) offers a less invasive approach, but the sensitivity of this technique has been unclear. To determine the sensitivity of FPEB for immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, we performed a retrospective clinicopathologic analysis of 97 patients who had undergone FPEB, of which 16 were positive for amyloid...
November 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/29125055/cerebral-amyloid-angiopathy-cerebral-microbleeds-and-implications-for-anticoagulation-decisions-the-need-for-a-balanced-approach
#7
Andreas Charidimou, Ashkan Shoamanesh, Rustam Al-Shahi Salman, Charlotte Cordonnier, Luke A Perry, Kevin N Sheth, Alessandro Biffi, Jonathan Rosand, Anand Viswanathan
Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/29093431/increased-prognostic-value-of-query-amyloid-late-enhancement-score-in-light-chain-cardiac-amyloidosis
#8
Ke Wan, Jiayu Sun, Yuchi Han, Hong Liu, Dan Yang, Weihao Li, Jie Wang, Wei Cheng, Qing Zhang, Zhi Zeng, Yucheng Chen
BACKGROUND: Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score...
November 2, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29093408/the-long-term-outcomes-after-vad-plus-sct-therapy-in-a-patient-with-al-amyloidosis-and-severe-factor-x-deficiency
#9
Dosuke Iwadate, Eiko Hasegawa, Junichi Hoshino, Noriko Hayami, Keiichi Sumida, Masayuki Yamanouchi, Akinari Sekine, Masahiro Kawada, Rikako Hiramatsu, Tstsuya Suwabe, Naoki Sawa, Mitsuhiro Yuasa, Atsushi Waki, Takeshi Fujii, Kenichi Ohashi, Kenmei Takaichi, Yoshifumi Ubara
A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary AL amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29093404/nationwide-survey-of-741-patients-with-systemic-amyloid-light-chain-amyloidosis-in-japan
#10
Chihiro Shimazaki, Hiroyuki Hata, Sinsuke Iida, Mitsuharu Ueda, Nagaaki Katoh, Yoshiki Sekishima, Shuichi Ikeda, Masahide Yazaki, Wakaba Fukushima, Yukio Ando
Objective To retrospectively investigate the clinical manifestations of systemic amyloid light-chain (AL) amyloidosis in Japanese patients and the treatment strategy for the condition. Methods We conducted a survey of Japanese AL patients, who were treated between January 1, 2012, and December 31, 2014. Results A total of 741 AL amyloidosis patients were included in this study (436 men and 305 women; median age: 65 years old, range: 31-93). The most frequently affected organ was the kidneys (n=542), followed by the heart (n=252), gastrointestinal (GI) tract (n=164), autonomic nervous system (n=131), liver (n=71), and peripheral nervous system (n=71)...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29093392/atraumatic-splenic-rupture-due-to-ectopic-extramedullary-hematopoiesis-after-autologous-stem-cell-transplantation-in-a-patient-with-al-amyloidosis
#11
Shuku Sato, Yotaro Tamai, Satomi Okada, Emiko Kannbe, Kotaro Takeda, Eri Tanaka
A 50-year-old man was diagnosed with multiple myeloma complicating AL amyloidosis. Splenic rupture was complicated during autologous stem cell transplantation (auto-SCT). Granulocyte colony-stimulating factor (G-CSF) was not administered. A pathological examination of the spleen revealed that CD34-positive cells were concentrated in the ruptured part of the splenic capsule. Hematopoietic cells were engrafted in the small gap between the capsule and amyloid protein deposition area of the spleen, which might have caused the splenic rupture in the absence of G-CSF administration...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29077753/correction-imaging-features-of-intracerebral-hemorrhage-with-cerebral-amyloid-angiopathy-systematic-review-and-meta-analysis
#12
Neshika Samarasekera, Mark Alexander Rodrigues, Pheng Shiew Toh, Rustam Al-Shahi Salman
[This corrects the article DOI: 10.1371/journal.pone.0180923.].
2017: PloS One
https://www.readbyqxmd.com/read/29067795/intramyocardial-inflammation-predicts-adverse-outcome-in-patients-with-cardiac-al-amyloidosis
#13
Christine S Siegismund, Felicitas Escher, Dirk Lassner, Uwe Kühl, Ulrich Gross, Friedrich Fruhwald, Philip Wenzel, Thomas Münzel, Norbert Frey, Reinhold P Linke, Heinz-Peter Schultheiss
AIMS: To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. METHODS AND RESULTS: We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy to as long as 36 months (mean 11.5 ± 12 months) and compared their outcome with information on all-cause mortality with or without proof of inflammation on EMB...
October 25, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29064094/cardiac-amyloidosis-is-associated-with-increased-aortic-stiffness
#14
Attila Nemes, Dóra Földeák, Péter Domsik, Anita Kalapos, Árpád Kormányos, Zita Borbényi, Tamás Forster
OBJECTIVE: Cardiac amyloidosis (CA) is as an infiltrative disorder primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The current study was designed to test whether alterations in ascending aortic elastic properties could be detected by echocardiography in CA patients, and to compare their results to controls. PATIENTS AND METHODS: We included 19 CA patients from which CA proved to be AL amyloidosis in 17 cases and transthyretin (TTR) amyloidosis in 2 cases...
October 24, 2017: Journal of Clinical Ultrasound: JCU
https://www.readbyqxmd.com/read/29055813/amyloid-%C3%AE-synaptotoxicity-is-wnt-pcp-dependent-and-blocked-by-fasudil
#15
Katherine J Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana I Rojo, Heledd H Jarosz-Griffiths, Iain A Watson, Weiming Xia, Mikhail Semenov, Peter Morin, Nigel M Hooper, Rod Porter, Jane Preston, Raya Al-Shawi, George Baillie, Simon Lovestone, Antonio Cuadrado, Michael Harte, Paul Simons, Deepak P Srivastava, Richard Killick
INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death. METHODS: We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29053948/nanoscale-imaging-reveals-big-role-for-iron-in-alzheimer-s-disease
#16
Scott Ayton, Simon A James, Ashley I Bush
In this issue of Cell Chemical Biology, Telling et al. (2017) apply advanced X-ray microscopy techniques to reveal magnetite iron species in plaques from a mouse model of Alzheimer's disease. The characterization of abnormal iron chemistry in the disease model highlights the potential for iron to combine with the β-amyloid peptide and accelerate the disease process.
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29045890/a-rhim-with-a-view-flying-with-functional-amyloids
#17
Sunny Shin, Sara Cherry
Recognition of bacterial peptidoglycan by the Drosophila IMD pathway triggers NF-κB activation and an associated immune response. In this issue of Immunity, Kleino et al. (2017) show that proteins in the IMD pathway form functional amyloids via a cryptic motif resembling the RHIM motif found in mammalian RIPK proteins. Amyloid formation can be negatively regulated, suggesting that it presents a regulatory point in multiple biological processes.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29042130/a-decay-of-the-adaptive-capacity-of-the-unfolded-protein-response-exacerbates-alzheimer-s-disease
#18
Yannis Gerakis, Claudio Hetz
Alterations in the buffering capacity of the proteostasis network are a salient feature of Alzheimer's disease, associated with the occurrence of chronic endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive programs through the induction of transcription factors such as X-box binding protein 1 (XBP1). A new study by Marcora et al used a fly model to study amyloid β pathogenesis in the secretory pathway of neurons...
September 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29037943/mesenchymal-stromal-cells-protect-human-cardiomyocytes-from-amyloid-fibril-damage
#19
Yi Lin, Marta Marin-Argany, Christopher J Dick, Keely R Redhage, Luis M Blancas-Mejia, Peggy Bulur, Greg W Butler, Michael C Deeds, Benjamin J Madden, Angela Williams, Jonathan S Wall, Allan Dietz, Marina Ramirez-Alvarado
BACKGROUND AIMS: Light chain (AL) amyloidosis is a protein misfolding disease characterized by extracellular deposition of immunoglobulin light chains (LC) as amyloid fibrils. Patients with LC amyloid involvement of the heart have the worst morbidity and mortality. Current treatments target the plasma cells to reduce further production of amyloid proteins. There is dire need to understand the mechanisms of cardiac tissue damage from amyloid to develop novel therapies. We recently reported that LC soluble and fibrillar species cause apoptosis and inhibit cell growth in human cardiomyocytes...
October 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29028503/unveiling-the-stimulatory-effects-of-tartrazine-on-human-and-bovine-serum-albumin-fibrillogenesis-spectroscopic-and-microscopic-study
#20
Nasser Abdulatif Al-Shabib, Javed Masood Khan, Mohammad A Alsenaidy, Abdulrahman M Alsenaidy, Mohd Shahnawaz Khan, Fohad Mabood Husain, Mohammad Rashid Khan, Mohammad Naseem, Priyankar Sen, Parvez Alam, Rizwan Hasan Khan
Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs7...
September 22, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
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