Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Background: Patients with transthyretin (TTR) cardiac amyloidosis demonstrate cardiac cachexia with progression of their cardiomyopathy, which is characterised by malnutrition and a heightened inflammatory state. How best to measure this condition is less well characterised. We investigated differences in survival among patients with ATTR cardiac amyloidosis by nutritional status as defined by modified BMI (mBMI) and by inflammatory state as defined by serum uric acid. ⋯ Serum uric acid was a univariate predictor of death (HR 1.27 per 1 mg/dL, 95% CI 1.114-1.455, p < .001). In multivariate Cox analysis, this association remained significant (HR 1.31 per 1 mg/dL increase, 95% CI 1.096-1.560, p = .003) as well as in a separate stepwise model controlling for potential confounders including daily diuretic use, uric acid lowering therapy, and renal dysfunction. Conclusions: Both nutritional status as measured by mBMI and inflammation as measured by serum uric acid are associated with survival in patients with TTR cardiac amyloidosis however only serum uric acid is an independent predictor of death.
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The Curated Protein Aggregation Database (CPAD) is a manually curated and open-access database dedicated to providing comprehensive information related to mechanistic, kinetic and structural aspects of protein and peptide aggregation. The database has been updated to CPAD 2.0 by significantly expanding datasets and improving the user-interface. ⋯ This database will help the scientific community (a) by facilitating research leading to improved understanding of protein aggregation, (b) by helping develop, validate and benchmark mechanistic and kinetic models of protein aggregation, and (c) by assisting experimentalists with design of their investigations and dissemination of data generated by their studies. CPAD 2.0 can be accessed at https://web.iitm.ac.in/bioinfo2/cpad2/index.html.
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From a clinical perspective, there is a need for a reliable and comprehensive list of diseases causing AA amyloidosis. This list could guide clinicians in the evaluation of patients with AA amyloidosis in whom an obvious cause is lacking. In this systematic review, a PubMed, Embase and Web of Science literature search were performed on causes of AA amyloidosis published in the last four decades. ⋯ Disease associations were categorized and 48 were listed as strong, 19 as weak, 23 as unclear, and 60 as unlikely. Most newly described diseases are not really unexpected because they often cause longstanding inflammation. Based on the spectrum of identified causes, a pragmatic diagnostic approach is proposed for the AA amyloidosis patient in whom an obvious underlying disease is lacking.
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Amyloidosis is an extremely rare event in rats. In this study, we report that lipopolysaccharide binding protein (LBP) is the most likely amyloidogenic protein in rat mammary amyloidosis. Histologically, corpora amylacea (CA) and stromal amyloid (SA) were observed in rat mammary glands, and needle-shaped amyloid (NA) was also observed on the surface or gap of CA and SA. ⋯ In the same analysis, LBP was detected as a prime candidate protein in NA, and NA was positive following immunohistochemistry and immunoelectron microscopy with anti-LBP antibody. Furthermore, synthetic peptides derived from rat LBP formed amyloid fibrils in vitro. Overall, these results provide evidence that LBP is an amyloid precursor protein of NA in rat mammary glands.