Articles: transthyretin.
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To evaluate the long-term efficacy and safety of diflunisal in late-onset familial amyloid polyneuropathy (FAP) in a Japanese endemic area. ⋯ Diflunisal might be effective especially for autonomic dysfunction in late-onset FAP with a TTR Val30Met mutation.
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The murine genes encoding transthyretin (TTR) and retinol binding protein (RBP) were independently silenced by targeted disruption more than 10 years ago. Studies of both strains showed surprisingly little impact on either thyroid function or retinoid metabolism. Silencing TTR led to a relatively mild behavioral phenotype. ⋯ There also appeared to be a major reduction in proliferating neuroblasts in the subventricular zone in both strains, which was also more severe in the Rbp4(-/-) mice. This is the first description of behavioral abnormalities in Rbp4(-/-)mice. The data also indicate that it is unlikely that the behaviors seen in Ttr(-/-) mice are related to its function as an RBP carrier.
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Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs. ⋯ We conclude that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.
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Multicenter Study Comparative Study
Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis.
Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. ⋯ In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.
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Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). ⋯ This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF).