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https://www.readbyqxmd.com/read/29775574/forms-and-phases-in-huntingtin-protein-aggregation
#1
Michael Elbaum
Using a combination of fluorescence microscopy and electron tomography, Peskett et al. (2018), in this issue of Molecular Cell, explore the nucleation of amyloid-like filaments from liquid-like condensates of huntingtin protein exon1 with disease-related polyQ extensions.
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29748430/epidemiology-of-al-amyloidosis-a-real-world-study-using-us-claims-data
#2
Tiffany P Quock, Tingjian Yan, Eunice Chang, Spencer Guthrie, Michael S Broder
Amyloid light-chain (AL) amyloidosis is a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to provide an up-to-date estimate of prevalence and incidence of AL amyloidosis in the United States. Using claims databases from years 2007 to 2015, adults ≥18 years old with AL amyloidosis were included if they had (1) at least 1 inpatient or 2 outpatient claims consistent with AL amyloidosis and (2) received 1 AL-specific treatment. Prevalence was calculated as the number of AL patients divided by the number of enrollees on June 30th of each calendar year...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29732485/role-of-melatonin-in-aluminum-related-neurodegenerative-disorders-a-review
#3
José L Esparza, Mercedes Gómez, José L Domingo
Aluminum (Al), a potentially neurotoxic element, provokes various adverse effects on human health such as dialysis dementia, osteomalacia, and microcytic anemia. It has been also associated with serious neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Parkinsonism dementia of Guam. The "aluminum hypothesis" of AD assumes that the metal complexes can potentiate the rate of aggregation of amyloid-β (Aβ), enhancing the toxicity of this peptide, and being able of contributing to the pathogenesis of AD...
May 7, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29721855/id1-and-sonic-hedgehog-mediate-cell-cycle-reentry-and-apoptosis-induced-by-amyloid-beta-peptide-in-post-mitotic-cortical-neurons
#4
A-Ching Chao, Chien-Hui Chen, Shih-Hsin Chang, Chao-Tzu Huang, Wei-Chao Hwang, Ding-I Yang
Amyloid beta-peptide (Aβ), the neurotoxic component of senile plaques in Alzheimer's disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aβs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al., Mol Neurobiol 53(2):793-809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aβ-induced Id1 and SHH contribute to cell cycle reentry leading to apoptosis in neurons...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29706312/metabolic-syndrome-marks-early-risk-for-cognitive-decline-with-apoe4-gene-variation-a-case-study
#5
Dawson Brown, Kelly J Gibas
A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks...
April 20, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29700090/cardiac-amyloidosis
#6
Ana Martinez-Naharro, Philip N Hawkins, Marianna Fontana
Systemic amyloidosis comprises an uncommon group of disorders caused by the extracellular deposition of misfolded proteins in various organs. Cardiac amyloid deposition, causing an infiltrative/restrictive cardiomyopathy, is a frequent feature of amyloidosis and a major determinant of survival. It may be the presenting feature of the disease or may be identified while investigating a patient presenting with other organ involvement. The need for a high index of suspicion and the critical importance of precise biochemical typing of the amyloid deposits is paramount in light of recent therapeutic advances that can significantly improve prognosis...
April 1, 2018: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/29697673/-solitary-epithelioid-hemangioendothelioma-concurrent-with-nodular-parenchymal-amyloidosis-of-the-lung-and-rosai-dorfman-disease
#7
O V Dolzhansky, E M Paltseva, M M Morozova, D V Bazarov, E V Boranov, D N Fedorov
The paper describes a case of solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal AL amyloidosis of the lung and Rosai-Dorfman disease in a 70-year-old woman. The core of the tumor was represented by bone tissue with dendriform ossification, as well as by amyloid that showed green apple birefringence at polarized light microscopy. The peripheral portions of the tumor and the myxohyaline stroma exhibited slit-like structures, epithelioid and fusiform cells with small cytoplasmic vacuoles...
2018: Arkhiv Patologii
https://www.readbyqxmd.com/read/29696194/rationale-and-design-of-dual-study-doxycycline-to-upgrade-response-in-light-chain-al-amyloidosis-dual-a-phase-2-pilot-study-of-a-two-pronged-approach-of-prolonged-doxycycline-with-plasma-cell-directed-therapy-in-the-treatment-of-al-amyloidosis
#8
Anita D'Souza, Kathryn Flynn, Saurabh Chhabra, Binod Dhakal, Mehdi Hamadani, Kirsten Jacobsen, Marcelo Pasquini, Dorothee Weihrauch, Parameswaran Hari
Light chain (AL) amyloidosis is a plasma cell neoplasm associated with insoluble fibril deposition from clonal immunoglobulin chains systemically. The disease is associated with high early mortality and morbidity owing to advanced organ deposition as well as lack of proven de-fibrillogenic therapies. Pre-clinical and retrospective clinical data suggests that doxycycline has benefit in AL amyloidosis. The ongoing DUAL study is a single center, open label, phase 2 study in which patients with AL amyloidosis who are undergoing clone-directed therapy for the underlying neoplasm with oral doxycycline given for 1 year to test the hypothesis that prolonged doxycycline use will be safe, feasible, and lead to reduced early mortality in systemic AL amyloidosis and hasten organ amyloid response...
December 2017: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29692592/revisiting-renal-amyloidosis-with-clinicopathological-characteristics-grading-and-scoring-a-single-institutional-experience
#9
Abhiram Kalle, Archana Gudipati, Sree Bhushan Raju, Karthik Kalidindi, Swarnalatha Guditi, Gangadhar Taduri, Megha S Uppin
INTRODUCTION: Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. MATERIALS AND METHODS: The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017...
April 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29685951/dual-therapy-for-a%C3%AE-amyloidosis-in-ad-a-successful-one-two-combo
#10
Tirth K Patel, David M Holtzman
In this issue, Chiang et al. (https://doi.org/10.1084/jem.20171484) make a notable contribution to Alzheimer disease (AD) therapeutics in a thorough and rigorous study demonstrating superior efficacy of dual therapy against Aβ in a mouse model of amyloid β deposition.
April 23, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29668344/phenotypic-plasticity-of-mesenchymal-stem-cells-is-crucial-for-mesangial-repair-in-a-model-of-immunoglobulin-light-chain-associated-mesangial-damage
#11
Guillermo A Herrera, Jiamin Teng, Chun Zeng, Hongzhi Xu, Man Liang, J Steven Alexander, Bing Liu, Chris Boyer, Elba A Turbat-Herrera
Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. The collagen IV rich matrix is replaced by tenascin...
April 18, 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29664336/left-ventricular-myocardial-deformation-on-cine-mr-images-relationship-to-severity-of-disease-and-prognosis-in-amyloid-light-chain-amyloidosis
#12
Ke Wan, Jiayu Sun, Dan Yang, Hong Liu, Jie Wang, Wei Cheng, Qing Zhang, Zhi Zeng, Tianjing Zhang, Andreas Greiser, Marie-Pierre Jolly, Yuchi Han, Yucheng Chen
Purpose To measure left ventricular (LV) myocardial strain with cine magnetic resonance (MR) imaging and a deformable registration algorithm (DRA) and to assess the prognostic value of myocardial strain in patients with light-chain (AL) amyloidosis. Materials and Methods In this prospective study, 78 consecutive patients with AL amyloidosis who underwent contrast material-enhanced cardiac MR imaging were enrolled at West China Hospital. LV myocardial strains and late gadolinium enhancement (LGE) were evaluated...
April 17, 2018: Radiology
https://www.readbyqxmd.com/read/29660165/usefulness-of-gastroduodenal-biopsy-in-the-differential-diagnosis-of-systemic-ah-amyloidosis-from-systemic-al-amyloidosis
#13
Shojiro Ichimata, Mikiko Kobayashi, Hisashi Shimojo, Nagaaki Katoh, Masahide Yazaki, Hiroyuki Kanno
AIMS: Immunoglobulin (Ig) heavy chain amyloidosis (AH amyloidosis) is Ig-related amyloidosis classified together with Ig light chain amyloidosis (AL amyloidosis). Compared with AL amyloidosis, patients with AH amyloidosis exhibit a better prognosis and they may not need an aggressive treatment. Thus, the accurate diagnosis is essential for management of Ig-related amyloidosis patients. For definite diagnosis of AH amyloidosis, biochemical analyses are usually needed. However, these analyses can be performed in limited facilities...
April 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29651545/extracardiac-18-f-florbetapir-imaging-in-patients-with-systemic-amyloidosis-more-than-hearts-and-minds
#14
T Wagner, J Page, M Burniston, A Skillen, J C Ross, R Manwani, D McCool, P N Hawkins, Ashutosh D Wechalekar
PURPOSE: 18 F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18 F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18 F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123 I-serum amyloid P component (SAP)...
April 12, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29651353/a-rare-case-of-systemic-al-amyloidosis-with-muscle-involvement-a-misleading-diagnosis
#15
Fabrizio Accardi, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, Roberta Costa, Laura Notarfranchi, Benedetta Dalla Palma, Franco Aversa, Vladimiro Pietrini, Giovanna Cenacchi, Nicola Giuliani
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29627865/advances-in-treatment-of-cardiac-amyloid
#16
REVIEW
Cherie N Dahm, R Frank Cornell, Daniel J Lenihan
Systemic amyloidosis represents a complex group of diseases with a common feature characterized by misfolded autologous proteins depositing into tissues or organs throughout the body. Light chain amyloidosis (AL) and transthyretin (TTR) amyloid are the two most prevalent forms of this disease that commonly results in cardiac amyloidosis. In both of these conditions, the myocardium is a frequent site of infiltration and end-organ involvement often with devastating consequences. With cardiac amyloidosis becoming an increasingly identified disease that has previously been under-recognized, the purpose of this comprehensive review is to focus on the diagnosis and treatment of these two types of cardiac amyloidosis including a contemporary update on currently available therapies being investigated in clinical trials...
April 7, 2018: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29627464/letter-to-the-editor
#17
Reza Khodarahmi
I read with great interest the paper by Dehvari and Ghahghaei (Dehvari and Ghahghaei, 2018 [1]). Their paper aimed to prove that biosynthesized AgNPs mediated by Pulicaria undulata L. has the capability in inhibiting amyloid fibril formation and thus could be considered as a therapeutic agent in the treatment of amyloidosis disorders. According to the literature (Jangholi et al., 2018 [2]), Thioflavin T (ThT) is a commonly used probe to monitor in vitro amyloid fibril formation. Also, since ThT fluorescence originates only from the bound population of the dye molecules, the several orders of magnitude increase in the fluorescence intensity makes ThT an unusually sensitive and efficient reporter...
April 5, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29621503/a-comparative-study-of-single-needle-and-coaxial-electrospun-amyloid-like-protein-nanofibers-to-investigate-hydrophilic-drug-release-behavior
#18
Gözde Kabay, Ceylan Demirci, Gizem Kaleli Can, Ahmet Ersin Meydan, Beyhan Günaydin Daşan, Mehmet Mutlu
In this study, nanofibers containing an amyloid-like bovine serum albumin (AL-BSA) carrier and a model drug (ampicillin) were produced by electrospinning. The release behavior of ampicillin was compared from electrospun nanofibers prepared as either coaxial or single-needle types. SEM images showed that the membranes had a uniform and smooth structure and the core/shell fibers were found to be thicker than the core fibers. Core/shell production was proved by transmission electron microscopy images. Fourier transform infrared spectroscopy indicated the existence of compatibility between ampicillin and the AL-BSA matrix...
April 2, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29615179/pulmonary-nodular-amyloidosis-mimicking-metastatic-lung-lesion-in-a-patient-with-colon-cancer
#19
Waseem M Hajjar, Tariq E Al-Johani, Mohammed A Jameel, Othman T Almutairi, Iftikhar Ahmed, Adnan W Hajjar, Sami A Al-Nassar
Amyloidosis is defined as abnormal aggregation of amyloid proteins. Amyloidosis can be localised or systemic affecting the lung, heart, spleen, liver and kidneys. The most common form of pulmonary amyloidosis is the nodular type. The disease is idiopathic and linked to many systemic diseases. The clinical manifestations and prognosis of respiratory tract amyloidosis depends on its etiology and anatomical location. Radiologically, the nodular pulmonary amyloidosis may appear as single or multiple nodules in any lobe, and, therefore, may mimic as primary pulmonary or metastatic neoplasms...
April 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29602877/taking-a-position-on-intramembrane-proteolysis
#20
M Joanne Lemieux
Decades of work have contributed to our in-depth mechanistic understanding of soluble proteases, but much less is known about the catalytic mechanism of intramembrane proteolysis due to inherent difficulties in both preparing and analyzing integral membrane enzymes and transmembrane substrates. New work from Naing et al. tackles this challenge by examining the catalytic parameters of an aspartyl intramembrane protease homologous to the enzyme that cleaves amyloid precursor protein, finding that both chemistry and register contribute to specificity in substrate cleavage...
March 30, 2018: Journal of Biological Chemistry
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