Identification of Immunoreactive Atrial Natriuretic Peptide in Atrial Amyloid
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The Study of the Formation of Oligomers and Amyloid Plaques from Amylin by Capillary Electrophoresis and Fluorescent Microchip E
University of Arkansas, Fayetteville ScholarWorks@UARK Biological and Agricultural Engineering Biological and Agricultural Engineering Undergraduate Honors Theses 5-2015 The tuds y of the formation of oligomers and amyloid plaques from Amylin by capillary electrophoresis and fluorescent microchip electrophoresis Shane Weindel University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/baeguht Part of the Engineering Commons Recommended Citation Weindel, Shane, "The tudys of the formation of oligomers and amyloid plaques from Amylin by capillary electrophoresis and fluorescent microchip electrophoresis" (2015). Biological and Agricultural Engineering Undergraduate Honors Theses. 25. http://scholarworks.uark.edu/baeguht/25 This Thesis is brought to you for free and open access by the Biological and Agricultural Engineering at ScholarWorks@UARK. It has been accepted for inclusion in Biological and Agricultural Engineering Undergraduate Honors Theses by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. The Study of the Formation of Oligomers and Amyloid Plaques from Amylin by Capillary Electrophoresis and Fluorescent Microchip Electrophoresis Shane Weindel, Biological Engineering Undergraduate Christa Hestekin, Chemical Engineering Assistant Professor Department of Biological & Agricultural Engineering 203 Engineering Hall 1 University of Arkansas Abstract Amylin, a pancreatic β-cell hormone, was the focus of this research project. This hormone is co-localized and co-secreted with insulin in response to nutrient stimuli. The hormone inhibits food intake, gastric emptying and glucagon secretion. Insulin and amylin appear to complement each other in the control of plasma glucose levels. Human amylin has a propensity to self-aggregate and to form insoluble bodies. -
Beta Amyloid Imaging with Positron Emission Tomography For
Corporate Medical Policy Beta Amyloid Imaging With Positron Emission Tomography for Alzheimer’s Disease File Name: beta_amyloid_imaging_with_positron_emission_tomography_for_alzheimers_disease Origination: 10/2014 Last CAP Review: 5/2021 Next CAP Review: 5/2022 Last Review: 5/2021 Description of Procedure or Service Three radioactive tracers (florbetapir F18, flutemetamol F18, florbetaben F18) that bind to beta amyloid and can be detected in vivo with positron emission tomography (PET) have been developed. This technology is being evaluated to detect beta amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer disease (AD) and/or other causes of cognitive decline. Background The diagnosis of AD is divided into 3 categories: possible, probable, and definite AD. A diagnosis of definite AD requires postmortem confirmation of AD pathology, including the presence of extracellular beta amyloid plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. There can be a range of beta amyloid plaques and neurofibrillary tanges on histopathology that support a low, intermediate or high probability of AD. Probable AD dementia is diagnosed clinically when the patient meets core clinical criteria for dementia and has a typical clinical course for AD. A typical clinical course is defined as an insidious onset, with the initial and most prominent cognitive deficits being either amnestic or nonamnestic, e.g., language, visuospatial, or executive function deficits, and a history of progressively worsening cognition over time. A diagnosis of possible AD dementia is made when the patient meets the core clinical criteria for AD dementia but has an atypical course or an etiologically mixed presentation. Mild cognitive impairment (MCI) may be diagnosed when there is a change in cognition, but impairment is insufficient for the diagnosis of dementia. -
A Guide to Transthyretin Amyloidosis
A Guide to Transthyretin Amyloidosis Authored by Teresa Coelho, Bo-Goran Ericzon, Rodney Falk, Donna Grogan, Shu-ichi Ikeda, Mathew Maurer, Violaine Plante-Bordeneuve, Ole Suhr, Pedro Trigo 2016 Edition Edited by Merrill Benson, Mathew Maurer What is amyloidosis? Amyloidosis is a systemic disorder characterized by extra cellular deposition of a protein-derived material, known as amyloid, in multiple organs. Amyloidosis occurs when native or mutant poly- peptides misfold and aggregate as fibrils. The amyloid deposits cause local damage to the cells around which they are deposited leading to a variety of clinical symptoms. There are at least 23 different proteins associated with the amyloidoses. The most well-known type of amyloidosis is associated with a hematological disorder, in which amyloid fibrils are derived from monoclonal immunoglobulin light-chains (AL amyloidosis). This is associated with a clonal plasma cell disorder, closely related to and not uncommonly co-existing with multiple myeloma. Chronic inflammatory conditions such as rheumatoid arthritis or chronic infections such as bronchiectasis are associated with chronically elevated levels of the inflammatory protein, serum amyloid A, which may misfold and cause AA amyloidosis. The hereditary forms of amyloidosis are autosomal dominant diseases characterized by deposition of variant proteins, in dis- tinctive tissues. The most common hereditary form is transthyretin amyloidosis (ATTR) caused by the misfolding of protein monomers derived from the tetrameric protein transthyretin (TTR). Mutations in the gene for TTR frequently re- sult in instability of TTR and subsequent fibril formation. Closely related is wild-type TTR in which the native TTR protein, particu- larly in the elderly, can destabilize and re-aggregate causing non- familial cases of TTR amyloidosis. -
Influence of Serum Amyloid a (SAA1) And
Influence of Serum Amyloid A (SAA1) and SAA2 Gene Polymorphisms on Renal Amyloidosis, and on SAA/ C-Reactive Protein Values in Patients with Familial Mediterranean Fever in the Turkish Population AYSIN BAKKALOGLU, ALI DUZOVA, SEZA OZEN, BANU BALCI, NESRIN BESBAS, REZAN TOPALOGLU, FATIH OZALTIN, and ENGIN YILMAZ ABSTRACT. Objective. To evaluate the effect of serum amyloid A (SAA) 1 and SAA2 gene polymorphisms on SAA levels and renal amyloidosis in Turkish patients with familial Mediterranean fever (FMF). Methods. SAA1 and SAA2 gene polymorphisms and SAA levels were determined in 74 patients with FMF (39 female, 35 male; median age 11.5 yrs, range 1.0–23.0). All patients were on colchicine therapy. SAA1 and SAA2 gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). SAA and C-reactive protein (CRP) values were measured and SAA/CRP values were calculated. Results. The median SAA level was 75 ng/ml (range 10.2–1500). SAA1 gene polymorphisms were: α/α genotype in 23 patients (31.1%), α/ß genotype in 30 patients (40.5%), α/γ genotype in one patient (1.4 %), ß/ß genotype in 14 patients (18.9%), ß/γ genotype in 5 patients (6.8 %), and γ/γ geno- type in one patient (1.4%). Of the 23 patients who had α/α genotype for the SAA1 polymorphism, 7 patients had developed renal amyloidosis (30.4%) compared to only one patient without this geno- type (1/51; 2.0%); p < 0.001. SAA2 had no effect on renal amyloidosis. SAA1 and SAA2 genotypes had no significant effect on SAA levels. -
Cerebral Amyloidosis, Amyloid Angiopathy, and Their Relationship to Stroke and Dementia
65 Cerebral amyloidosis, amyloid angiopathy, and their relationship to stroke and dementia ∗ Jorge Ghiso and Blas Frangione β-pleated sheet structure, the conformation responsi- Department of Pathology, New York University School ble for their physicochemical properties and tinctoreal of Medicine, New York, NY, USA characteristics. So far, 20 different proteins have been identified as subunits of amyloid fibrils [56,57,60 (for review and nomenclature)]. Although collectively they Cerebral amyloid angiopathy (CAA) is the common term are products of normal genes, several amyloid precur- used to define the deposition of amyloid in the walls of sors contain abnormal amino acid substitutions that can medium- and small-size leptomeningeal and cortical arteries, arterioles and, less frequently, capillaries and veins. CAA impose an unusual potential for self-aggregation. In- is an important cause of cerebral hemorrhages although it creased levels of amyloid precursors, either in the cir- may also lead to ischemic infarction and dementia. It is a culation or locally at sites of deposition, are usually the feature commonly associated with normal aging, Alzheimer result of overexpression, defective clearance, or both. disease (AD), Down syndrome (DS), and Sporadic Cerebral Of all the amyloid proteins identified, less than half are Amyloid Angiopathy. Familial conditions in which amyloid known to cause amyloid deposition in the central ner- is chiefly deposited as CAA include hereditary cerebral hem- vous system (CNS), which in turn results in cognitive orrhage with amyloidosis of Icelandic type (HCHWA-I), fa- decline, dementia, stroke, cerebellar and extrapyrami- milial CAA related to Aβ variants, including hereditary cere- dal signs, or a combination of them. -
Expression of Atrial and Brain Natriuretic Peptides and Their Genes in Hearts of Patients with Cardiac Amyloidosis
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector 754 JACC Vol. 31, No. 4 March 15, 1998:254–65 Expression of Atrial and Brain Natriuretic Peptides and Their Genes in Hearts of Patients With Cardiac Amyloidosis GENZOU TAKEMURA, MD,*† YOSHIKI TAKATSU, MD,* KIYOSHI DOYAMA, MD,‡ HIROSHI ITOH, MD,‡ YOSHIHIKO SAITO, MD,‡ MASATOSHI KOSHIJI, MD,† FUMITAKA ANDO, MD,* TAKAKO FUJIWARA, MD,§ KAZUWA NAKAO, MD,‡ HISAYOSHI FUJIWARA, MD† Hyogo, Gifu and Kyoto, Japan Objectives. We investigated the expression of atrial natriuretic secretory granules in ventricular myoctyes of the patients with peptide (ANP) and brain natriuretic peptide (BNP) and their cardiac amyloidosis, but not in ventricular myocytes from the genes in the hearts of patients with cardiac amyloidosis and those normal control subjects. Double immunocytochemical analysis with isolated atrial amyloidosis. revealed the co-localization of ANP and BNP in the same granules Background. The expression of ANP and BNP is augmented in and that isolated atrial amyloid fibrils were immunoreactive for the ventricles of failing or hypertrophied hearts, or both. The ANP and BNP, whereas ventricular amyloid fibrils were negative expression of ANP and BNP in the ventricles of hearts with for both peptides. Both ANP mRNA and BNP mRNA were cardiac amyloidosis, which is hemodynamically similar to restric- expressed in the ventricles of the patients with cardiac amyloid- tive cardiomyopathy, is not yet known. ANP is the precursor osis but not in the normal ventricles. The autopsy study of four protein of isolated atrial amyloid. patients with cardiac amyloidosis revealed an almost transmural Methods. -
Recognizing TTR-FAP Transthyretin Familial Amyloid Polyneuropathy
This version is Global RC approved and local adaptation and approval is mandatory before distribution. Countries are responsible for language accuracy. Content to be updated with local information and labeling as required. Recognizing TTR-FAP Transthyretin Familial Amyloid Polyneuropathy About TTR-FAP TTR-FAP is a rare, genetic, TTR-FAP is caused by a mutation in the transthyretin gene, which can result in abnormal and unstable progressive and fatal transthyretin proteins. 2,3 neurodegenerative disease affecting an estimated 10,000 people worldwide.1 TTR-FAP – A Disease of Protein Misfolding Free Tetramer Folded Misfolded Toxic Intermediates Monamer Monamer & Amyloid Fibrils TTR-FAP affects men and women equally. Monamer Aggregation Misfolding Functional TTR Structures TTR Structures Symptoms usually begin to affect Associated with Pathology people in their 30s. These abnormal proteins build up and form toxic This varies with genetics and structures called amyloid fibrils, which may deposit in the peripheral nervous system, leading to a decline in ethnic background.2,3 The life neurologic function, or in other parts of the body, such expectancy for someone who as the heart, digestive system, and kidneys.2,3,4,5,6,7 is diagnosed with TTR-FAP is said to be about 10 years.13 Where is TTR-FAP Most Prevalent? There are clusters of TTR-FAP patients in Portugal, Japan, and Sweden.8 TTR-FAP is also found in countries such as the United States, various countries in Europe (e.g., France, Italy, Spain, Germany, and UK), Brazil, and Taiwan.9 Prevalence of TTR-FAP may vary by country of origin and by the type of TTR gene mutation.10 Symptoms of TTR-FAP Symptoms vary, but often, the feet Later, weakness gets worse in the and legs are affected first—with legs.11 The arms may be affected pain, tingling, numbness, or loss of too, starting at the figertips.11 the ability to feel hot and cold.11 Why Early Diagnosis is Key Although the disease affects people differently, it typically gets worse over time and can progress rapidly. -
Breakthroughs in Antemortem Diagnosis of Neurodegenerative Diseases COMMENTARY Glenn C
COMMENTARY Breakthroughs in antemortem diagnosis of neurodegenerative diseases COMMENTARY Glenn C. Tellinga,1 The World Health Organization forecasts that within 2 Abnormal cytoplasmic accumulation of a normally sol- decades neurodegenerative disorders will eclipse can- uble and unfolded protein called α-synuclein is the cer to become the foremost cause of death in the de- hallmark of diseases referred to as synucleinopathies. veloped world after cardiovascular disease. Accurate Neuronal deposition of α-synuclein aggregates in Lewy detection of pathological processes goes hand in hand bodies occurs in Parkinson’s disease (PD) and dementia with the goals of treatment and prevention and, in light with Lewy bodies (DLB). Yet another protein—the prion of their protracted but worsening clinical progression, protein (PrP)—is central to a group of interrelated dis- the earlier a diagnosis can be made the better. How- orders commonly referred to as prion diseases. ever, the challenge underlying accurate detection of Since the concept underlying the diagnostic ap- neurodegenerative diseases during their clinical phase proach taken by Metrick et al. (1) derives from studies is that specific biomarkers are not present at high of prions, it is worth reviewing what we have learned enough concentrations for routine detection in acces- about PrP and the applicability of these findings to sible specimens. Consequently, it has only been pos- other proteopathic diseases. The prion disorders are sible to definitively diagnose these conditions by transmissible neurodegenerative diseases affecting examination of brain pathology after death. The paper animals and humans. The most common human form by Metrick et al. (1) in PNAS addresses the issue of is Creutzfeldt–Jakob disease (CJD) which occurs most improved antemortem biomarker detection for a frequently as a sporadic, rapidly progressive condition spectrum of neurological disorders, using assays of older individuals. -
Mass Spectrometric Determination of the Effect of Surface Deactivation on Membranes Used for In-Situ Sampling of Cerebrospinal Fluid (CSF)
Supplementary Materials Mass Spectrometric Determination of the Effect of Surface Deactivation on Membranes Used for In-Situ Sampling of Cerebrospinal Fluid (CSF) Torgny Undin 1, Andreas P Dahlin 2, Jonas Bergquist 1, and Sara Bergström Lind 1,* 1 Department of Chemistry-BMC, Analytical Chemistry, Uppsala University, PO Box 599, SE-751 24 Uppsala, Sweden; [email protected] (T.U.); [email protected] (J.B.) 2 Department of Engineering Sciences, Uppsala University, PO Box 534, SE-751 21 Uppsala, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-18-4713693 Supplementary Table Table A Heat map of identified adsorbed proteins on coated membranes in group A. A time resolved map of all identified proteins that adsorbs to the surface providing deeper information about the adsorption behavior of the individual proteins compared to the more schematic Fig. 2. The three colors in the heat map indicate zero (white), one (light green) or two or more (dark green) unique peptides identified for a particular protein. A protein must be identified by two peptides at least one time point to be considered identified. Protein 15 30 60 120 240 480 Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 - [CO3_HUMAN] 2 2 2 2 2 2 Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 - [ALBU_HUMAN] 2 2 2 2 2 2 Coagulation factor V OS=Homo sapiens GN=F5 PE=1 SV=4 - [FA5_HUMAN] 2 2 2 2 2 2 Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=2 - [CO4A_HUMAN] 2 2 2 2 2 2 Clusterin OS=Homo sapiens GN=CLU PE=1 SV=1 - [CLUS_HUMAN] 2 2 2 2 2 2 Fibulin-1 -
Acute-Phase Serum Amyloid a Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study
Cardiovascular and Metabolic Risk ORIGINAL ARTICLE Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study 1,2 6 CAROLA MARZI, MPH H.-ERICH WICHMANN, MD, PHD ype 2 diabetes is preceded by a 2,3 4,7 CORNELIA HUTH, PHD MICHAEL RODEN, MD 4 2,3 differential activation of compo- CHRISTIAN HERDER, PHD ANNETTE PETERS, PHD T 2,3 1,2 nents of the innate immune system JENS BAUMERT, PHD HARALD GRALLERT, PHD 2,3 8 (1,2). Serum amyloid A (SAA) is a sensi- BARBARA THORAND, PHD WOLFGANG KOENIG, MD 5 1,9 tive marker of the acute inflammatory WOLFGANG RATHMANN, MD THOMAS ILLIG, PHD 2,3 CHRISTA MEISINGER, MD state. Its acute-phase isoform (A-SAA) is up-regulated up to 1,000-fold in response to inflammatory stimuli such as trauma, – OBJECTIVEdWe sought to investigate whether elevated levels of acute-phase serum amyloid infection, injury, and stress (3 5). The A (A-SAA) protein precede the onset of type 2 diabetes independently of other risk factors, high inductive capacity, along with the including parameters of glucose metabolism. fact that genes and proteins are highly conserved throughout the evolution of RESEARCH DESIGN AND METHODSd Within the population-based Cooperative vertebrates and invertebrates, suggests Health Research in the Region of Augsburg (KORA) S4 study, we measured A-SAA concentrations that A-SAA plays a key role in pathogen in 836 initially nondiabetic subjects (55–74 years of age) without clinically overt inflammation who participated in a 7-year follow-up examination including an oral glucose tolerance test. -
Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review
Journal of Clinical Medicine Article Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review Hélène Vergneault 1 , Alexandre Terré 1, David Buob 2,†, Camille Buffet 3 , Anael Dumont 4, Samuel Ardois 5, Léa Savey 1, Agathe Pardon 6,‡, Pierre-Antoine Michel 7, Jean-Jacques Boffa 7,†, Gilles Grateau 1,† and Sophie Georgin-Lavialle 1,*,† 1 Internal Medicine Department and National Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA), APHP, Tenon Hospital, Sorbonne University, 4 rue de la Chine, 75020 Paris, France; [email protected] (H.V.); [email protected] (A.T.); [email protected] (L.S.); [email protected] (G.G.) 2 Department of Pathology, APHP, Tenon Hospital, Sorbonne University, 4 rue de la Chine, 75020 Paris, France; [email protected] 3 Thyroid Pathologies and Endocrine Tumor Department, APHP, Pitié-Salpêtrière Hospital, Sorbonne University, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; [email protected] 4 Department of Internal Medicine, Caen University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France; [email protected] 5 Department of Internal Medecine, Rennes Medical University, 2 rue Henri le Guilloux, 35000 Rennes, France; [email protected] 6 Dialysis Center, CH Sud Francilien, 40 Avenue Serge Dassault, 91100 Corbeil-Essonnes, France; [email protected] 7 Citation: Vergneault, H.; Terré, A.; Department of Nephrology, APHP, Tenon Hospital, 4 rue de la Chine, 75020 Paris, France; [email protected] (P.-A.M.); [email protected] (J.-J.B.) Buob, D.; Buffet, C.; Dumont, A.; * Correspondence: [email protected]; Tel.: +33-156016077 Ardois, S.; Savey, L.; Pardon, A.; † Groupe de Recherche Clinique amylose AA Sorbonne Université- GRAASU. -
The Expression of Genes Contributing to Pancreatic Adenocarcinoma Progression Is Influenced by the Respective Environment – Sagini Et Al
The expression of genes contributing to pancreatic adenocarcinoma progression is influenced by the respective environment – Sagini et al Supplementary Figure 1: Target genes regulated by TGM2. Figure represents 24 genes regulated by TGM2, which were obtained from Ingenuity Pathway Analysis. As indicated, 9 genes (marked red) are down-regulated by TGM2. On the contrary, 15 genes (marked red) are up-regulated by TGM2. Supplementary Table 1: Functional annotations of genes from Suit2-007 cells growing in pancreatic environment Categoriesa Diseases or p-Valuec Predicted Activation Number of genesf Functions activationd Z-scoree Annotationb Cell movement Cell movement 1,56E-11 increased 2,199 LAMB3, CEACAM6, CCL20, AGR2, MUC1, CXCL1, LAMA3, LCN2, COL17A1, CXCL8, AIF1, MMP7, CEMIP, JUP, SOD2, S100A4, PDGFA, NDRG1, SGK1, IGFBP3, DDR1, IL1A, CDKN1A, NREP, SEMA3E SERPINA3, SDC4, ALPP, CX3CL1, NFKBIA, ANXA3, CDH1, CDCP1, CRYAB, TUBB2B, FOXQ1, SLPI, F3, GRINA, ITGA2, ARPIN/C15orf38- AP3S2, SPTLC1, IL10, TSC22D3, LAMC2, TCAF1, CDH3, MX1, LEP, ZC3H12A, PMP22, IL32, FAM83H, EFNA1, PATJ, CEBPB, SERPINA5, PTK6, EPHB6, JUND, TNFSF14, ERBB3, TNFRSF25, FCAR, CXCL16, HLA-A, CEACAM1, FAT1, AHR, CSF2RA, CLDN7, MAPK13, FERMT1, TCAF2, MST1R, CD99, PTP4A2, PHLDA1, DEFB1, RHOB, TNFSF15, CD44, CSF2, SERPINB5, TGM2, SRC, ITGA6, TNC, HNRNPA2B1, RHOD, SKI, KISS1, TACSTD2, GNAI2, CXCL2, NFKB2, TAGLN2, TNF, CD74, PTPRK, STAT3, ARHGAP21, VEGFA, MYH9, SAA1, F11R, PDCD4, IQGAP1, DCN, MAPK8IP3, STC1, ADAM15, LTBP2, HOOK1, CST3, EPHA1, TIMP2, LPAR2, CORO1A, CLDN3, MYO1C,