Disease relevance of Amyloidosis

• Resolution of acquired factor X deficiency and amyloidosis with melphalan and prednisone therapy [1].
• The finding that PN-2/A beta PP is a potent inhibitor of Factor IXa could help to explain the spontaneous intracerebral hemorrhages seen in patients with hereditary cerebral hemorrhage with amyloidosis Dutch-type where there is an extensive accumulation of PN-2/A beta PP in their cerebral blood vessels [2].
• Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy [3].
• Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin [4].
• No genetic association between this family and amyloidosis and Portuguese families with familial amyloid polyneuropathy is known [5].

Psychiatry related information on Amyloidosis

• Alzheimer's disease is an amyloidosis, a condition in which certain proteins or protein fragments precipitate in various tissues as amyloid, fibrillar aggregates with a beta-pleated sheet conformation [6].
• The term "prion dementia" has been proposed to replace "spongiform encephalopathy", to accommodate the existence of atypical forms of these "prion protein" (PrP) cerebral amyloidoses that may not show spongiform changes in the brain [7].
• ACT was not found in the amyloid deposits in primary or secondary amyloidosis, familial and amyloidotic polyneuropathy or Creutzfeldt-Jakob disease (non-beta-protein amyloidoses), but was found (together with beta-protein) in Alzheimer's disease, Down's syndrome, normal aging, and hereditary cerebral hemorrhage with amyloidosis of Dutch origin [8].

High impact information on Amyloidosis

• Only the most highly destabilized TTR variants are subjected to ER-associated degradation (ERAD) and then only in certain tissues, providing insight into tissue selective amyloidosis [9].
• CONCLUSIONS: Therapy with melphalan and prednisone results in objective responses and prolonged survival as compared with colchicine in patients with primary amyloidosis [10].
• A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine [10].
• Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans [11].
• Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene [12].

Chemical compound and disease context of Amyloidosis

• Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein [13].
• Two families with hereditary renal amyloidosis were found to have a novel mutation in the fibrinogen A alpha chain gene [14].
• Thus, a high serum level of FP, as found in normal females or diethylstilbestrol-treated males, was associated with enhanced amyloidosis [15].
• Effect of a single dose of dimethyl sulphoxide on renal amyloidosis [16].
• In systemic amyloidosis, a fatal disorder for which there is no effective treatment, the extracellular protein deposits are composed of amyloid fibrils together with a non-fibrillar glycoprotein, amyloid P component (AP) [17].

Biological context of Amyloidosis

• Because only SAA2-derived products deposit in mouse amyloid tissues, the resistance of SJL mice to amyloidosis seems to be due to defective SAA2 gene expression [18].
• In order to explore the mechanism of SAA isotype-specific amyloid protein AA deposition, the molecular kinetics of the serum amyloid proteins were examined in CBA mice during casein induction of amyloidosis [19].
• A DNA polymorphic site, 5' to the serum amyloid P component gene, has been found to be significantly associated with amyloidosis in juvenile arthritic patients [20].
• Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals [21].
• The complete amino acid sequence of three related amyloid proteins (Mr 14,000, 10,000, and 5,000) derived from tissues of a Jewish patient who suffered from a variant of familial polyneuropathic amyloidosis was determined [22].

Anatomical context of Amyloidosis

• To investigate the role of fixed macrophages in amyloidogenesis and to establish more definitively that amyloid deposition is attributable to faulty processing of the precursor protein rather than aberrant synthesis, secondary amyloidosis was induced in C57BL/6J mice by serial injections of casein [23].
• Since some forms of secondary amyloidosis are caused by deposition in tissues of peptides derived from the SAA and leukocytes seem to be involved in this process, we investigated the effect of human SAA on human monocytes and polymorphonuclear cells (PMN) [24].
• PATIENTS: 65 patients with AL amyloidosis and urinary protein excretion greater than 1 g/24 h who received dose-intensive intravenous melphalan and autologous blood stem-cell transplantation between 1 July 1994 and 30 June 1998 [25].
• Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils [26].
• Neuropathologically, the common denominator is a cerebral prion protein amyloidosis; however, there is significant variability in the pattern of amyloid deposition in regions of the central nervous system among reported families [27].

Gene context of Amyloidosis

• Thus, the study emphasizes the importance of SAA gene structure in determining susceptibility to amyloidosis [18].
• In contrast, overexpression of human wild-type APP (APPwt mice) resulted in predominantly parenchymal amyloidosis, similar to that seen in AD [28].
• Inbred strains of mice provide a model for studies of the pathogenesis of amyloid A (AA) amyloidosis [29].
• Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice [30].
• Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene [31].
• Country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in FMF [32].

Analytical, diagnostic and therapeutic context of Amyloidosis

• Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component [33].
• Systemic amyloidosis was induced consistently in mice by intramuscular injection of syngeneic organ (liver and kidney) extracts mixed with CFA six times at weekly intervals [34].
• beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, a complication of long-term hemodialysis patients [35].
• Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis [36].
• Three of 4 patients with localized tracheobronchial amyloidosis required Nd:YAG (neodymium:yttrium-aluminum-garnet) laser therapy for obstructive symptoms. "Senile" amyloid deposition was an incidental finding in some patients at autopsy [37].

References