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https://www.readbyqxmd.com/read/29349534/psoriasis-from-pathogenesis-to-targeted-therapies
#1
REVIEW
Curdin Conrad, Michel Gilliet
Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization...
January 18, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29348121/endothelial-cell-derived-von-willebrand-factor-but-not-platelet-derived-promotes-atherosclerosis-in-apolipoprotein-e-deficient-mice
#2
Prakash Doddapattar, Nirav Dhanesha, Mehul R Chorawala, Chandler Tinsman, Manish Jain, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29348025/pet-mr-imaging-of-malondialdehyde-acetaldehyde-epitopes-with-a-human%C3%A2-antibody-detects-clinically%C3%A2-relevant-atherothrombosis
#3
Max L Senders, Xuchu Que, Young Seok Cho, Calvin Yeang, Hannah Groenen, Francois Fay, Claudia Calcagno, Anu E Meerwaldt, Simone Green, Phuong Miu, Mark E Lobatto, Thomas Reiner, Zahi A Fayad, Joseph L Witztum, Willem J M Mulder, Carlos Pérez-Medina, Sotirios Tsimikas
BACKGROUND: Oxidation-specific epitopes (OSEs) are proinflammatory, and elevated levels in plasma predict cardiovascular events. OBJECTIVES: The purpose of this study was to develop novel positron emission tomography (PET) probes to noninvasively image OSE-rich lesions. METHODS: An antigen-binding fragment (Fab) antibody library was constructed from human fetal cord blood. After multiple rounds of screening against malondialdehyde-acetaldehyde (MAA) epitopes, the Fab LA25 containing minimal nontemplated insertions in the CDR3 region was identified and characterized...
January 23, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29346172/apremilast-use-in-a-case-of-cicatricial-ectropion-secondary-to-severe-lamellar-ichthyosis
#4
Jean-Paul J Abboud, Alexander Whittington, Masih Ahmed, Jesse T Himebaugh, Lee A Wiley, Ahmad Haffar, John Nguyen
Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry thickened skin surface scales. Ocular manifestations of ichthyosis include cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely corneal perforation. Topical emollients, anti-inflammatory ointments, and systemic retinoids have been used to control the disease process, while surgical correction with donor graft has been reserved for severe cases involving corneal exposure. The authors report a case of a Caucasian male with lamellar ichthyosis with severe bilateral upper and lower eyelid cicatricial ectropion and corneal ulceration requiring surgical correction...
January 17, 2018: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/29345339/the-role-of-cdk5-mediated-drp1-phosphorylation-in-a%C3%AE-1-42-induced-mitochondrial-fission-and-neuronal-apoptosis
#5
Miao-Yu Guo, Lei Shang, Yang-Yang Hu, Li-Ping Jiang, Yu-Ying Wan, Qin-Qin Zhou, Kun Zhang, Hong-Fei Liao, Jing-Lin Yi, Xiao-Jian Han
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29341269/characterization-of-a-3xtg-ad-mouse-model-of-alzheimer-s-disease-with-the-senescence-accelerated-mouse-prone-8-samp8-background
#6
Jessica Virgili, Meryem Lebbadi, Cyntia Tremblay, Isabelle St-Amour, Caroline Pierrisnard, Audrey Faucher-Genest, Vincent Emond, Carl Julien, Frédéric Calon
No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Since old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging...
January 17, 2018: Synapse
https://www.readbyqxmd.com/read/29341259/child-syndrome-mimicking-verrucous-nevus-in-a-chinese-patient-responded-well-to-the-topical-therapy-of-compound-of-simvastatin-and-cholesterol
#7
Xia Yu, Jia Zhang, Yan Gu, Dan Deng, Zhouwei Wu, Lei Bao, Ming Li, Zhirong Yao
BACKGROUND: Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD syndrome is caused by mutations in NSDHL gene, which involves in cholesterol synthesis. OBJECTIVES: To verify the diagnosis of CHILD syndrome and seek effective pathogenesis-based therapy with little side effects. METHOD: We comprehensively evaluated the patient's conditions...
January 17, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29339169/the-timing-of-p2y12-inhibitor-initiation-in-the-treatment-of-acs-does-the-evidence-exist-in-this-era
#8
REVIEW
Harsh Golwala, Deepak L Bhatt
The majority of acute coronary syndromes (ACS) are well characterized as a consequence of plaque rupture and subsequent thrombosis. Antiplatelet agents targeting inhibition of P2Y12 receptors on the platelets have shown to reduce future risk of cardiovascular events in this patient population. However, the timing of initiation of these agents, in particular, in patients managed with invasive strategy with percutaneous coronary interventions (PCI) is debatable. The data supporting pretreatment with antiplatelet agents prior to PCI in ACS patients dates to trials performed >15 years ago, wherein the time to PCI was >5 days, and henceforth, the utility of pretreatment with these agents in the contemporary era remains uncertain...
January 12, 2018: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/29338754/molecular-and-functional-signatures-in-a-novel-alzheimer-s-disease-mouse-model-assessed-by-quantitative-proteomics
#9
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29336270/in-silico-ligand-based-identification-of-novel-acetylcholinesterase-inhibitors-against-alzheimer-s-disease-ad
#10
Mohammad Usman Mirza, Nazia Ikram, Nauman Mazhar, Kanzal Iman, Mehwish Riaz, Mohammad A Kamal
Alzheimer disease (AD) is a hot research topic currently across the world, characterized by the formation of β-amyloid plaques and neurofibrillary tangles. Inhibition of acetylcholinesterase (AChE) has gained much importance since the discovery of the involvement of peripheral anionic site (PAS) as an allosteric regulator of AChE. Progression of this neurodegenerative disorder causes a deficit in the cholinergic activity that leads towards cognitive decline. Therapeutic interventions in AD are largely focused upon AChE inhibitors designed essentially to prevent the loss of cholinergic function...
January 15, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29335450/copper-sulfide-nanoparticles-as-a-photothermal-switch-for-trpv1-signaling-to-attenuate-atherosclerosis
#11
Wen Gao, Yuhui Sun, Michelle Cai, Yujie Zhao, Wenhua Cao, Zhenhua Liu, Guanwei Cui, Bo Tang
Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29332908/optical-coherence-tomography-guidance-in-management-of-acute-coronary-syndrome-caused-by-plaque-erosion
#12
Haibo Jia, Takashi Kubo, Takashi Akasaka, Bo Yu
For several decades, most physicians have believed that acute coronary syndrome (ACS) is caused by coronary thrombosis resulting from rupture of vulnerable plaque characterized by a thin fibrous cap overlying a large necrotic core and massive inflammatory cell infiltration. However, nearly one-third of ACS cases are caused by plaque erosion characterized by intact fibrous cap, less or absent necrotic core, less inflammation, and large lumen. Because of the limitations of current imaging modalities, including angiography and intravascular ultrasound, the importance of plaque erosion as a cause of acute coronary events is less well known...
January 13, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#13
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332037/increased-vulnerability-of-the-hippocampus-in-transgenic-mice-overexpressing-app-and-triple-repeat-tau
#14
Andrew Arner, Edward Rockenstein, Michael Mante, Jazmin Florio, Deborah Masliah, Bahar Salehi, Anthony Adame, Cassia Overk, Eliezer Masliah, Robert A Rissman
 Alzheimer's disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between Aβ and 4R tau in double transgenic mice, but few, if any, have examined the effects of Aβ with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29330812/evaluation-of-the-effect-of-alogliptin-on-tissue-characteristics-of-the-carotid-wall-subanalysis-of-the-spead-a-trial
#15
Yoko Irie, Naoto Katakami, Tomoya Mita, Mitsuyoshi Takahara, Taka-Aki Matsuoka, Masahiko Gosho, Hirotaka Watada, Iichiro Shimomura
INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray-scale median (GSM) reflects its composition and low-GSM plaque is considered to be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue characteristics of the carotid wall, in patients with type 2 diabetes (T2DM). METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A trial, a randomized controlled trial that demonstrated the beneficial effect of alogliptin treatment on the progression of carotid intima-media thickness in patients with T2DM with no past history of apparent cardiovascular disease...
January 12, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29327503/noncoding-rnas-in-alzheimer-s-disease
#16
REVIEW
M Laura Idda, Rachel Munk, Kotb Abdelmohsen, Myriam Gorospe
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Despite intense efforts to develop drugs for preventing and treating AD, no effective therapies are available as yet, posing a growing burden at the personal, medical, and socioeconomic levels. AD is characterized by the production and aggregation of amyloid β (Aβ) peptides derived from amyloid precursor protein (APP), the presence of hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic inflammation leading to neuronal loss...
January 12, 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29326510/isolation-and-typing-of-streptococcus-mutans-and-streptococcus-sobrinus-from-caries-active-subjects
#17
Hamzah Abdulrahman Salman, R Senthilkumar, Khalid Imran, K Panneer Selvam
Background: Streptococcus mutans and Streptococcus sobrinus are main etiological agents of dental caries. Aim: The aim of the study was to isolate, identify, characterize, and determine the minimum inhibitory concentration (MIC) of S. mutans and S. sobrinus from caries-active subjects. Materials and Methods: Sixty-five plaque samples were collected from caries-active subjects aged between 35 and 44 years, processed and cultured on mitis salivarius bacitracin agar...
October 2017: Contemporary Clinical Dentistry
https://www.readbyqxmd.com/read/29326316/fibronectin-containing-extra-domain-a-induces-plaque-destabilization-in-the-innominate-artery-of-aged-apolipoprotein-e-deficient-mice
#18
Prakash Doddapattar, Manish Jain, Nirav Dhanesha, Steven R Lentz, Anil K Chauhan
OBJECTIVE: Fibronectin containing extra domain A (Fn-EDA) is an endogenous ligand of TLR4 (toll-like receptor 4) and is abundant in the extracellular matrix of advanced atherosclerotic lesions in human and mice. Irrespective of sex, deletion of Fn-EDA reduces early atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. However, the contribution of Fn-EDA in advanced atherosclerosis remains poorly characterized. We determined the contribution of Fn-EDA in advanced atherosclerotic lesions of aged (1-year-old) Apoe-/- mice...
January 11, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29322650/molecular-characterization-of-the-%C3%AE-amyloid-4-10-epitope-of-plaque-specific-a%C3%AE-antibodies-by-affinity-mass-spectrometry-using-alanine-site-mutation
#19
Raluca Ștefănescu, Loredana Lupu, Marilena Manea, Roxana E Iacob, Michael Przybylski
Alzheimer disease is a neurodegenerative disease affecting an increasing number of patients worldwide. Current therapeutic strategies are directed to molecules capable to block the aggregation of the β-amyloid(1-42) (Aβ) peptide and its shorter naturally occurring peptide fragments into toxic oligomers and amyloid fibrils. Aβ-specific antibodies have been recently developed as powerful antiaggregation tools. The identification and functional characterization of the epitope structures of Aβ antibodies contributes to the elucidation of their mechanism of action in the human organism...
January 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29322178/early-genetic-diagnosis-of-neurofibromatosis-type-2-from-skin-plaque-plexiform-schwannomas-in-childhood
#20
Elisabeth Castellanos, Adrià Plana, Cristina Carrato, Meritxell Carrió, Inma Rosas, Emilio Amilibia, Francesc Roca-Ribas, Cristina Hostalot, Alicia Castillo, Andrea Ros, Ariadna Quer, Juan Luis Becerra, Hector Salvador, Conxi Lázaro, Ignacio Blanco, Eduard Serra, Isabel Bielsa
Importance: Neurofibromatosis type 2 (NF2) is a devastating genetic condition characterized by the development of multiple tumors of the nervous system. An early diagnosis of individuals with NF2 would facilitate treatment and reduction of disease impact because most severe effects of the disease do not usually develop before adolescence. Little attention has traditionally been paid to dermatological signs in NF2. However, skin plaques are commonly seen in patients with NF2, normally appearing either at birth or early childhood, providing an opportunity for early NF2 detection and testing...
January 10, 2018: JAMA Dermatology
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