Lista de obras - MacRae F. Linton - Dominio Público Uruguay

6-Mercaptopurine, monocytes, and atherosclerosis

artículo científico publicado en 2010

A Genetic Approach to the Association Between PCSK9 and Sepsis

artículo científico publicado en 2019

A case of severe acquired hypertriglyceridemia in a 7-year-old girl.

artículo científico publicado en 2017

A new age of discovery for plasma lipoproteins

artículo científico publicado en 2007

A pathway-dependent on apoE, ApoAI, and ABCA1 determines formation of buoyant high-density lipoprotein by macrophage foam cells

artículo científico publicado en 2007

ACAT inhibition: bad for macrophages, good for smooth muscle cells?

artículo científico publicado en 2005

ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages

artículo científico publicado en 2004

ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages

artículo científico publicado en 2005

Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis

artículo científico publicado en 2002

Absence of regulated splicing of fibronectin EDA exon reduces atherosclerosis in mice.

artículo científico publicado en 2007

Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages

artículo científico publicado en 2005

Administration of N-Acyl-Phosphatidylethanolamine Expressing Bacteria to Low Density Lipoprotein Receptor Mice Improves Indices of Cardiometabolic Disease

artículo científico publicado en 2019

Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis

scientific article published on 01 June 2019

Angiotensin II amplifies macrophage-driven atherosclerosis

artículo científico publicado en 2004

Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques

artículo científico publicado en 2007

Angiotensin-induced abdominal aortic aneurysms in hypercholesterolemic mice: role of serum cholesterol and temporal effects of exposure

artículo científico publicado en 2014

Antiatherogenic effects of angiotensin receptor antagonism in mild renal dysfunction

artículo científico publicado en 2005

ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects

artículo científico publicado en 2004

Apolipoprotein E and Reverse Cholesterol Transport: The Role of Recycling in Plasma and Intracellular Lipid Trafficking

Are statins diabetogenic? ⬇️

artículo científico publicado el 1 de julio de 2011

Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection

Atherosclerosis following renal injury is ameliorated by pioglitazone and losartan via macrophage phenotype.

artículo científico publicado en 2015

Atherosclerosis in chronic kidney disease: the role of macrophages

artículo científico publicado en 2010

B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice

artículo científico publicado en 2002

Benzo[a]pyrene Potentiates the Pathogenesis of Abdominal Aortic Aneurysms in Apolipoprotein E Knockout Mice ⬇️

artículo científico publicado el 1 de enero de 2012

Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice

artículo científico publicado en 2010

Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice

artículo científico publicado en 2005

Cyclooxygenase products and atherosclerosis

artículo científico publicado en 2008

Cyclooxygenase-1 deficiency in bone marrow cells increases early atherosclerosis in apolipoprotein E- and low-density lipoprotein receptor-null mice

artículo científico publicado en 2005

Cyclooxygenase-2 and atherosclerosis

artículo científico publicado en 2002

Cyclooxygenase-2 and inflammation in atherosclerosis

artículo científico publicado en 2004

Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis

artículo científico publicado en 2002

Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse

artículo científico publicado en 2007

Dyslipidemias in Children ⬇️

artículo científico publicado el 8 de febrero de 2012

Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis

artículo científico publicado en 2016

Elevated high-density lipoprotein (HDL) levels due to hepatic lipase mutations do not reduce cardiovascular disease risk: another strike against the HDL dogma

artículo científico publicado en 2009

Evidence of metabolic syndrome in lean children with premature pubarche at diagnosis

artículo científico publicado en 2008

Exercise is Associated With Increased Small HDL Particle Concentration and Decreased Vascular Stiffness in Rheumatoid Arthritis

scientific article published on 01 December 2018

Failure of ACAT inhibition to retard atherosclerosis

artículo científico publicado en 2006

Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance

artículo científico publicado en 2003

High-Density Lipoproteins in Kidney Disease ⬇️

artículo científico

High-density lipoprotein therapeutics and cardiovascular prevention ⬇️

artículo científico publicado el 17 de agosto de 2010

Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms.

artículo científico publicado en 2016

Identification of small proline-rich repeat protein 3 as a novel atheroprotective factor that promotes adaptive Akt signaling in vascular smooth muscle cells

artículo científico publicado en 2014

Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus ⬇️

scientific journal article

Impaired secretion of apolipoprotein E2 from macrophages

artículo científico publicado en 2007

Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice

artículo científico publicado en 2003

Inhibition of apolipoprotein(a) synthesis by farnesoid X receptor and fibroblast growth factor 15/19: a step toward selective lipoprotein(a) therapeutics

artículo científico publicado en 2012

Insights into atherosclerosis using nanotechnology

artículo científico publicado en 2010

Interplay between apolipoprotein E and scavenger receptor class B type I controls coronary atherosclerosis and lifespan in the mouse

artículo científico publicado en 2005

Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells

artículo científico publicado en 2006

Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts

artículo científico publicado en 2015

Killing two birds with one stone, maybe: CETP inhibition increases both high-density lipoprotein levels and insulin secretion

artículo científico publicado en 2013

Lentiviral transduction of apoAI into hematopoietic progenitor cells and macrophages: applications to cell therapy of atherosclerosis

artículo científico publicado en 2008

Lipoprotein subclasses and particle size determined by nuclear magnetic resonance spectroscopy in systemic lupus erythematosus

artículo científico publicado en 2008

Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis

artículo científico publicado en 2010

Local effects of human PCSK9 on the atherosclerotic lesion

artículo científico publicado en 2015

Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice

artículo científico publicado en 2019

Loss of Rictor in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice

artículo científico publicado en 2018

Loss of SPRR3 in ApoE-/- mice leads to atheroma vulnerability through Akt dependent and independent effects in VSMCs.

artículo científico publicado en 2017

Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis

artículo científico publicado en 2013

Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent

artículo científico publicado en 2011

Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

artículo científico publicado en 2016

Macrophage IKKα Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis

artículo científico publicado en 2016

Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation

artículo científico publicado en 2010

Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis

artículo científico publicado en 2015

Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL.

artículo científico publicado en 2015

Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters.

artículo científico publicado en 2003

Macrophage apolipoprotein E reduces atherosclerosis and prevents premature death in apolipoprotein E and scavenger receptor-class BI double-knockout mice

artículo científico publicado en 2005

Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice

artículo científico publicado en 2014

Macrophage expression of peroxisome proliferator-activated receptor-alpha reduces atherosclerosis in low-density lipoprotein receptor-deficient mice

artículo científico publicado en 2007

Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis

artículo científico publicado en 2011

Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice

artículo científico publicado en 2014

Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania

artículo científico publicado en 2010

Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation

scientific article published on 01 February 2019

Novel Domain Interaction Regulates Secretion of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Protein ⬇️

artículo científico publicado el 25 de octubre de 2011

Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice

artículo científico publicado en 2011

Oral retinoids and plasma lipids

artículo científico publicado en 2013

Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease.

artículo científico publicado en 2010

Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I

scientific journal article

Physiological expression of macrophage apoE in the artery wall reduces atherosclerosis in severely hyperlipidemic mice

artículo científico publicado en 2002

Physiological relevance of apolipoprotein E recycling: studies in primary mouse hepatocytes

artículo científico publicado en 2005

Premature coronary-artery atherosclerosis in systemic lupus erythematosus

artículo científico publicado en 2003

Proatherogenic role for NK cells revealed

artículo científico publicado en 2004

Progressively decreasing plasma high-density lipoprotein cholesterol levels preceding diagnosis of smoldering myeloma

scientific article published on 13 April 2020

Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and -independent mechanisms

artículo científico publicado en 2014

Quantitative Estimates of the Variability of In Vivo Sonographic Measurements of the Mouse Aorta for Studies of Abdominal Aortic Aneurysms and Related Arterial Diseases ⬇️

artículo científico publicado el 1 de junio de 2011

Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E–Deficient Mice

artículo científico publicado en 2004

Quantum dot mediated imaging of atherosclerosis

artículo científico publicado en 2009

Rapid quantification of murine ABC mRNAs by real time reverse transcriptase-polymerase chain reaction

artículo científico publicado en 2002

Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity

artículo científico publicado en 2020

Reduced ABCA1-mediated cholesterol efflux and accelerated atherosclerosis in apolipoprotein E-deficient mice lacking macrophage-derived ACAT1.

artículo científico publicado en 2005

Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice

artículo científico publicado en 2004

Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor

artículo científico publicado en 2008

Renal dysfunction potentiates foam cell formation by repressing ABCA1.

artículo científico publicado en 2009

Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges

artículo científico publicado en 2012

Response by Mueller et al to Letter Regarding Article, "Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque M

artículo científico publicado en 2019

Response to Duell et al.

artículo científico publicado en 2014

Response to letter regarding article, "Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and -independent mecha

artículo científico publicado en 2015

Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase

scientific article published on 30 August 2007

SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis

artículo científico publicado en 2017

Scavenging Reactive Lipids to Prevent Oxidative Injury

scientific article published on 30 September 2020

Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr-/- mice

artículo científico publicado en 2020

Selective macrophage ascorbate deficiency suppresses early atherosclerosis ⬇️

artículo científico publicado el 23 de octubre de 2010

Self-association of human PCSK9 correlates with its LDLR-degrading activity

artículo científico publicado en 2008

Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation

scientific article published on 20 May 2013

Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI.

artículo científico publicado en 2007

Sex-Specific Parental Effects on Offspring Lipid Levels

artículo científico publicado en 2015

Sorting out the complexities of reverse cholesterol transport: CETP polymorphisms, HDL, and coronary disease

scientific article published on 01 September 2006

Targeting cardiovascular risk in patients with diabetes: management of dyslipidemia

artículo científico publicado en 2008

The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment: evidence for multiple redundant pathways

artículo científico publicado en 2004

The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I.

artículo científico publicado en 2005

The recycling of apolipoprotein E in primary cultures of mouse hepatocytes. Evidence for a physiologic connection to high density lipoprotein metabolism

artículo científico publicado en 2003

The role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy

artículo científico publicado en 2004

Tie1 attenuation reduces murine atherosclerosis in a dose-dependent and shear stress–specific manner ⬇️

artículo científico publicado el 7 de marzo de 2011

Transiently heightened angiotensin II has distinct effects on atherosclerosis and aneurysm formation in hyperlipidemic mice

scientific article published on 14 July 2005

Unique pathway for cholesterol uptake in fat cells

artículo científico publicado en 2004

Lista de obras de MacRae F. Linton

6-Mercaptopurine, monocytes, and atherosclerosis

A Genetic Approach to the Association Between PCSK9 and Sepsis

A case of severe acquired hypertriglyceridemia in a 7-year-old girl.

A new age of discovery for plasma lipoproteins

A pathway-dependent on apoE, ApoAI, and ABCA1 determines formation of buoyant high-density lipoprotein by macrophage foam cells

ACAT inhibition: bad for macrophages, good for smooth muscle cells?

ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages

ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages

Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis

Absence of regulated splicing of fibronectin EDA exon reduces atherosclerosis in mice.

Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages

Administration of N-Acyl-Phosphatidylethanolamine Expressing Bacteria to Low Density Lipoprotein Receptor Mice Improves Indices of Cardiometabolic Disease

Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis

Angiotensin II amplifies macrophage-driven atherosclerosis

Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques

Angiotensin-induced abdominal aortic aneurysms in hypercholesterolemic mice: role of serum cholesterol and temporal effects of exposure

Antiatherogenic effects of angiotensin receptor antagonism in mild renal dysfunction

ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects

Apolipoprotein E and Reverse Cholesterol Transport: The Role of Recycling in Plasma and Intracellular Lipid Trafficking

Are statins diabetogenic? ⬇️

Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection

Atherosclerosis following renal injury is ameliorated by pioglitazone and losartan via macrophage phenotype.

Atherosclerosis in chronic kidney disease: the role of macrophages

B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice

Benzo[a]pyrene Potentiates the Pathogenesis of Abdominal Aortic Aneurysms in Apolipoprotein E Knockout Mice ⬇️

Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice

Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice

Cyclooxygenase products and atherosclerosis

Cyclooxygenase-1 deficiency in bone marrow cells increases early atherosclerosis in apolipoprotein E- and low-density lipoprotein receptor-null mice

Cyclooxygenase-2 and atherosclerosis

Cyclooxygenase-2 and inflammation in atherosclerosis

Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis

Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse

Dyslipidemias in Children ⬇️

Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis

Elevated high-density lipoprotein (HDL) levels due to hepatic lipase mutations do not reduce cardiovascular disease risk: another strike against the HDL dogma

Evidence of metabolic syndrome in lean children with premature pubarche at diagnosis

Exercise is Associated With Increased Small HDL Particle Concentration and Decreased Vascular Stiffness in Rheumatoid Arthritis

Failure of ACAT inhibition to retard atherosclerosis

Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance

High-Density Lipoproteins in Kidney Disease ⬇️

High-density lipoprotein therapeutics and cardiovascular prevention ⬇️

Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms.

Identification of small proline-rich repeat protein 3 as a novel atheroprotective factor that promotes adaptive Akt signaling in vascular smooth muscle cells

Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus ⬇️

Impaired secretion of apolipoprotein E2 from macrophages

Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice

Inhibition of apolipoprotein(a) synthesis by farnesoid X receptor and fibroblast growth factor 15/19: a step toward selective lipoprotein(a) therapeutics

Insights into atherosclerosis using nanotechnology

Interplay between apolipoprotein E and scavenger receptor class B type I controls coronary atherosclerosis and lifespan in the mouse

Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells

Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts

Killing two birds with one stone, maybe: CETP inhibition increases both high-density lipoprotein levels and insulin secretion

Lentiviral transduction of apoAI into hematopoietic progenitor cells and macrophages: applications to cell therapy of atherosclerosis

Lipoprotein subclasses and particle size determined by nuclear magnetic resonance spectroscopy in systemic lupus erythematosus

Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis

Local effects of human PCSK9 on the atherosclerotic lesion

Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice

Loss of Rictor in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice

Loss of SPRR3 in ApoE-/- mice leads to atheroma vulnerability through Akt dependent and independent effects in VSMCs.

Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis

Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent

Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

Macrophage IKKα Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis

Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation

Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis

Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL.

Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters.

Macrophage apolipoprotein E reduces atherosclerosis and prevents premature death in apolipoprotein E and scavenger receptor-class BI double-knockout mice

Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice

Macrophage expression of peroxisome proliferator-activated receptor-alpha reduces atherosclerosis in low-density lipoprotein receptor-deficient mice

Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis

Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice

Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania

Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation

Novel Domain Interaction Regulates Secretion of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Protein ⬇️

Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice

Oral retinoids and plasma lipids

Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease.