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Journal of Ultrasound Sep 2023Cardiac involvement from amyloidosis is of growing interest in the overall literature. Despite cardiac amyloidosis (CA) has been considered for a long time a rare... (Review)
Review
Cardiac involvement from amyloidosis is of growing interest in the overall literature. Despite cardiac amyloidosis (CA) has been considered for a long time a rare disease, the diagnostic awareness is increasing mainly thanks to the improvement of diagnostic softwares and of imaging techniques such as cardiac magnetic resonance (CMR). Some authors have observed an increase of prevalence rate of CA; moreover it's often underestimated because clinical manifestations are aspecific. The interstitial infiltration of the left ventricle has been extensively studied, while the involvement of the right ventricle (RV) has been less investigated. Involvement of the RV, even in the absence of pulmonary hypertension or clearly left ventricle infiltration, plays an important role as prognostic factor and is useful to achieve an early diagnosis. Therefore, the use of fast and low-cost diagnostic methods such as ultrasound strain of the right ventricle could be used to recognize cardiac amyloidosis early. Herein the importance of evaluating the right ventricular involvement, which can predict the most severe course of the disease also without overt clinical manifestations. The role of imaging, in particular of echocardiography, CMR, and scintigraphy is here reported.
Topics: Humans; Amyloidosis; Heart; Prognosis; Echocardiography; Disease Progression
PubMed: 37162729
DOI: 10.1007/s40477-023-00789-1 -
International Journal of Molecular... Sep 2018Amyloids result from the aggregation of a set of diverse proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they... (Review)
Review
Amyloids result from the aggregation of a set of diverse proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being exerted in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs with contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which makes it plausible that more effective drugs will be developed in the future.
Topics: Amyloid; Amyloidosis; Animals; Drug Design; Drug Development; Humans; Lipid Metabolism; Molecular Targeted Therapy; Protein Aggregates; Protein Aggregation, Pathological
PubMed: 30205618
DOI: 10.3390/ijms19092677 -
The Journal of Biological Chemistry May 2022Low-complexity domains (LCDs) of proteins have been shown to self-associate, and pathogenic mutations within these domains often drive the proteins into amyloid...
Low-complexity domains (LCDs) of proteins have been shown to self-associate, and pathogenic mutations within these domains often drive the proteins into amyloid aggregation associated with disease. These domains may be especially susceptible to amyloidogenic mutations because they are commonly intrinsically disordered and function in self-association. The question therefore arises whether a search for pathogenic mutations in LCDs of the human proteome can lead to identification of other proteins associated with amyloid disease. Here, we take a computational approach to identify documented pathogenic mutations within LCDs that may favor amyloid formation. Using this approach, we identify numerous known amyloidogenic mutations, including several such mutations within proteins previously unidentified as amyloidogenic. Among the latter group, we focus on two mutations within the TRK-fused gene protein (TFG), known to play roles in protein secretion and innate immunity, which are associated with two different peripheral neuropathies. We show that both mutations increase the propensity of TFG to form amyloid fibrils. We therefore conclude that TFG is a novel amyloid protein and propose that the diseases associated with its mutant forms may be amyloidoses.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Computational Biology; Humans; Mutation; Proteome
PubMed: 35405097
DOI: 10.1016/j.jbc.2022.101920 -
Philosophical Transactions of the Royal... Feb 2001Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and cause... (Review)
Review
Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and cause disease. Although about 20 different unrelated proteins can form amyloid fibrils in vivo, all such fibrils share a common cross-beta core structure. Some natural wild-type proteins are inherently amyloidogenic, form fibrils and cause amyloidosis in old age or if present for long periods at abnormally high concentration. Other amyloidogenic proteins are acquired or inherited variants, containing amino-acid substitutions that render them unstable so that they populate partly unfolded states under physiological conditions, and these intermediates then aggregate in the stable amyloid fold. In addition to the fibrils, amyloid deposits always contain the non-fibrillar pentraxin plasma protein, serum amyloid P component (SAP), because it undergoes specific calcium-dependent binding to amyloid fibrils. SAP contributes to amyloidogenesis, probably by stabilizing amyloid fibrils and retarding their clearance. Radiolabelled SAP is an extremely useful, safe, specific, non-invasive, quantitative tracer for scintigraphic imaging of systemic amyloid deposits. Its use has demonstrated that elimination of the supply of amyloid fibril precursor proteins leads to regression of amyloid deposits with clinical benefit. Current treatment of amyloidosis comprises careful maintenance of impaired organ function, replacement of end-stage organ failure by dialysis or transplantation, and vigorous efforts to control underlying conditions responsible for production of fibril precursors. New approaches under development include drugs for stabilization of the native fold of precursor proteins, inhibition of fibrillogenesis, reversion of the amyloid to the native fold, and dissociation of SAP to accelerate amyloid fibril clearance in vivo.
Topics: Amyloidosis; Glycosaminoglycans; Humans; Immunoglobulin Light Chains; Serum Amyloid P-Component
PubMed: 11260801
DOI: 10.1098/rstb.2000.0766 -
Canadian Respiratory Journal 2014
Topics: Adult; Amyloidosis; Bronchial Diseases; Humans; Male; Radiography; Trachea; Tracheal Diseases
PubMed: 24524114
DOI: 10.1155/2014/624615 -
Amyloid : the International Journal of... Mar 2017Autopsy identifies lung involvement in 58-92% of patients with the most prevalent forms of systemic amyloidoses. In the absence of lung biopsies, amyloid lung disease...
BACKGROUND
Autopsy identifies lung involvement in 58-92% of patients with the most prevalent forms of systemic amyloidoses. In the absence of lung biopsies, amyloid lung disease often goes unrecognized. Report of a death following transbronchial biopsies in a patient with systemic amyloidosis cautioned against the procedure in this patient cohort. We reviewed our experience with transbronchial biopsies in patients with amyloidosis to determine the safety and utility of bronchoscopic lung biopsies.
METHODS
We identified patients referred to the Amyloidosis Center at Boston Medical Center with lung amyloidosis diagnosed by transbronchial lung biopsies (TBBX). Amyloid typing was determined by immunohistochemistry or mass spectrometry. Standard end organ assessments, including pulmonary function test (PFT) and chest tomography (CT) imaging, and extra-thoracic biopsies established the extent of disease.
RESULTS
Twenty-five (21.7%) of 115 patients with lung amyloidosis were diagnosed by TBBX. PFT classified 33.3% with restrictive physiology, 28.6% with obstructive disease, and 9.5% mixed physiology; 9.5% exhibited isolated diffusion defects while 19% had normal pulmonary testing. Two view chest or CT imaging identified focal opacities in 52% of cases and diffuse interstitial disease in 48%. Amyloid type and disease extent included 68% systemic AL disease, 16% localized (lung limited) AL disease, 12% ATTR disease, and 4% AA amyloidosis. Fluoroscopy was not used during biopsy. No procedure complications were reported.
CONCLUSIONS
Our case series of 25 patients supports the use of bronchoscopic transbronchial biopsies for diagnosis of parenchymal lung amyloidosis. Normal PFTs do not rule out the histologic presence of amyloid lung disease.
Topics: Adult; Aged; Amyloid; Amyloidosis; Biopsy; Female; Humans; Lung; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Respiratory Function Tests
PubMed: 28393574
DOI: 10.1080/13506129.2017.1301917 -
JACC. Cardiovascular Imaging Nov 2019
Topics: Amyloidosis; Biopsy; Cardiomyopathies; Extracellular Space; Fibrosis; Humans; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Tomography, Emission-Computed; Ventricular Remodeling
PubMed: 31699304
DOI: 10.1016/j.jcmg.2019.10.002 -
Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis.Acta Medica Okayama Oct 2023To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine...
To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.
Topics: Male; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Retrospective Studies; Amyloidosis; Stomach Diseases
PubMed: 37899266
DOI: 10.18926/AMO/65978 -
Revista de La Facultad de Ciencias... Mar 2022Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in... (Review)
Review
METHOD
Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation.
SUGGESTED EXPLANATION
A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used.
HOW TO USE THESE GUIDELINES
Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care.
SUMMARY OF RECOMMENDATIONS
For patients with suspected amyloidosis, it is recommended: Electrocardiogram be used as a preliminary assessment for all patients with amyloidosis. Doppler echocardiography conventional be used as the initial image of the first choice for cardiac amyloidosis in patients diagnosed with suspected heart involvement due to amyloidosis. Echocardiographic strain diagnosis for patients with amyloidosis prompted by conventional echocardiography or uncertain. Cardiac magnetic resonance imaging (MRI) be used for the diagnosis of cardiac amyloidosis in patients with previous studies suggesting or uncertain amyloidosis. T1 mapping technology for cardiac MRI to diagnose myocardial amyloidosis as an alternative to MRI, for patients with kidney failure or contraindication to other studies Cardiac MRI examination with T1 localization technique for patients who have previously studied amyloidosis, and measure the extracellular volume and quantify the degree of cardiac involvement in order to diagnose and measure the cardiac involvement caused by amyloidosis.
IT IS SUGGESTED
Cardiac MRI with T1 mapping technique and extracellular volume measurement for the early diagnosis of amyloidosis in patients with previous studies suggestive of amyloidosis. Measurement of type B-type natriuretic peptide measurement be used for screening and diagnosis of cardiac amyloidosis. Pyrophosphate scintigraphy to make a preliminary diagnosis of patients with suspected cardiac amyloidosis, so as to distinguish ATTR (positive) from other patients.
Topics: Amyloidosis; Cardiomyopathies; Echocardiography; Humans; Magnetic Resonance Imaging; Myocardium; Practice Guidelines as Topic
PubMed: 35312257
DOI: 10.31053/1853.0605.v79.n1.30897 -
International Journal of Clinical and... Aug 2009Neurodegenerative diseases are characterized by selective and progressive loss of specific populations of neurons, which determines the clinical presentation. The same... (Review)
Review
Neurodegenerative diseases are characterized by selective and progressive loss of specific populations of neurons, which determines the clinical presentation. The same neuronal populations can be affected in a number of different disorders. Given that the clinical presentation reflects the particular population of neurons that are targets of the disease process, it is clear that for any given clinical syndrome, more than one neurodegenerative disease can account for the clinical syndrome. Because of this clinical ambiguity, for the purpose of this brief review neurodegenerative disorders are classified according to the underlying molecular pathology rather than their clinical presentation. The major neurodegenerative diseases can be classified into amyloidoses, tauopathies, alpha-synucleinopathies and TDP-43 proteinopathies.
Topics: Amyloidosis; Gene Expression; Humans; Neurodegenerative Diseases; Neurons; Pathology, Molecular; Syndrome; TDP-43 Proteinopathies; Tauopathies; alpha-Synuclein
PubMed: 19918325
DOI: No ID Found