Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Transthyretin (TTR) is a 127-amino acid residue protein synthesized mainly in the liver and in several minor sites, including the choroid plexus and the eye. In plasma, TTR circulates as a homotetramer and transports the hormone thyroxine and the retinol-binding protein-vitamin A complex. It is hypothesized that amino acid substitutions in TTR destabilize the tetramer by causing each subunit toform intermediates that may self-associate into amyloid fibrils. ⋯ Previous studies have shown that the TTR Arg104His variant is non-pathologic. It appeared to provide a protective effect in another compound heterozygous case (TTR Val30Met/Arg104His). However, the TTR Arg104His variant when presented with the TTR Thr59Lys variant did not seem to have any protective role.
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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.