Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Comparative Study
Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis.
We evaluated the role of electron microscopy and immuno-electron microscopy studies on abdominal fat fine-needle biopsy samples in diagnosis and characterization of cardiac amyloidosis. The series consists of 15 patients with echocardiographic evidence of "restrictive cardiomyopathy" suspected to be due to amyloidosis. Patients underwent: clinical examination, electrocardiography, 2-D and Doppler echocardiography, immunofixation of serum and urine for detection of monoclonal immunoglobulins, and abdominalfat biopsies that were investigated with polarized light (Congo red), electron and immuno-electron microscopy using specific antibodies to kappa and lambda light chains, apolipoprotein A1, serum amyloid A (SAA), and transthyretin (TTR). ⋯ Immuno-electron microscopy revealed TTR immuno-labelling in 2 patients with accidental monoclonal components, and a A reaction in I patient without monoclonal components. TTR and apolipoprotein A1 positive cases carried missense mutations in the corresponding genes. Our results demonstrate that amyloid deposits are present in the abdominalfat of patients suspected to have cardiac amyloidosis and that immuno-electron microscopy was able to characterize the amyloid protein in all cases.
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Case Reports
Cardiac amyloidosis associated with the transthyretin Ile122 mutation in a Caucasian family.
The Ile122 transthyretin variant associated with restrictive cardiomyopathy has been described in African-Americans and estimated to be present in approximately 4% of the Black population. We report the first American-Caucasian family with cardiomyopathy due to the TTR Ile122 mutation. The high prevalence of this mutation in the Black population and the discovery that it may cause disease in other ethnic populations highlights the importance of considering this autosomal dominant systemic amyloidosis in all individuals with restrictive cardiomyopathy. Inadequate diagnosis combined with inappropriate treatment may have a significant impact on morbidity and mortality.
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The standardization and clinical validation of the measurement of beta-amyloid(1-42) (Abeta42) in cerebrospinal fluid (CSF), plasma and urine is described using a commercially available sandwich-type ELISA with 21F12 and 3D6 as monoclonal antibodies. The INNOTEST beta-amyloid(1-42) allows the specific and reliable measurement of(1-42) amyloid peptides in CSF and plasma. The Abeta42 concentrations in serum and urine were below the detection limit. ⋯ No correlation was found in AD patients between CSF and plasma concentrations of Abeta42 or between CSF Abeta42 levels and blood-brain-barrier function. The quantitative outcome of the test is in part dependent on confounding factors such as tube type, freeze/thaw cycles, temperature of incubation, standard preparation protocol, and antibody selection. Notwithstanding these aspects, it emerged that Abeta42 is a useful biochemical marker for the diagnosis of AD patients, but there is a need for an international Abeta standard, a universally accepted protocol for CSF preparation, and a thorough evaluation of assay performance in function of the boundary conditions.
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The gene frequency of the transthyretin (TTR) mutation (Val122Ile) was studied in African and African-American populations. The African populations analyzed included the Zulu and Xhosa of South Africa, and Yorubas from the city of Ibadan, Nigeria. ⋯ The Val122Ile TTR mutation was identified in 1 of 55 Zulu, 0 of 34 Xhosa, 0 of 9 Nigerian subjects, 5 of 51 Veteran patients, and 3 of 103 newborns. Assuming the 2.91% prevalence in newborns to be the norm, there is a significant increased prevalence in the VA patient population.