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Missense mutations are identified in the oncostatin M-specific receptor (OSMR) gene which encodes the oncostatin M receptor beta (OSMRbeta) in three families. It is observed that the OSMR data in individuals with family primary localized cutaneous amyloidosis (FPLCA) represent the first human germline mutations in the cytokine receptor complex.

The human cerebral and systemic amyloidoses and prion-associated spongiform encephalopathies are acquired or inherited protein folding disorders in which normally soluble proteins or peptides are converted into fibrillar aggregates. This is a nucleation-dependent process that can be initiated or accelerated by fibril seeds formed from homologous or heterologous amyloidogenic precursors that serve as an amyloid enhancing factor (AEF) and has pathogenic significance in that disease may be transmitted by oral ingestion or parenteral administration of these conformationally altered components. Except for infected brain tissue, specific dietary sources of AEF have not been identified. Here we report that commercially available duck- or goose-derived foie gras contains birefringent congophilic fibrillar material composed of serum amyloid A-related protein that acted as a potent AEF in a transgenic murine model of secondary (amyloid A protein) amyloidosis. When such mice were injected with or fed amyloid extracted from foie gras, the animals developed extensive systemic pathological deposits. These experimental data provide evidence that an amyloid-containing food product hastened the development of amyloid protein A amyloidosis in a susceptible population. On this basis, we posit that this and perhaps other forms of amyloidosis may be transmissible, akin to the infectious nature of prion-related illnesses. amyloid protein A amyloidosis | amyloid-enhancing factor | protein aggregation | rheumatoid arthritis | transmissibility

Extracellular amyloid [beta] peptides (A[beta]s) have long been thought to be a primary cause of Alzheimer's disease (AD). Now, detection of intracellular neuronal A[[beta].sub.1-42] accumulation before extracellular A[beta] deposits questions the relevance of intracellular peptides in AD. In the present study, we directly address whether intracellular A[beta] is toxic to human neurons. Microinjections of A[[beta].sub.1-42] peptide or a cDNA-expressing cytosolic A[[beta].sub.1-42] rapidly induces cell death of primary human neurons. In contrast, A[[beta].sub.1-40], A[[beta].sub.40-1], or A[[beta].sub.42-1] peptides, and cDNAs expressing cytosolic A[[beta].sub.1-40] or secreted A[[beta].sub.1-42] and A[[beta].sub.1-40], are not toxic. As little as a 1-pM concentration or 1500 molecules/cell of A[[beta].sub.1-42] peptides is neurotoxic. The nonfibrillized and fibrillized A[[beta].sub.1-42] peptides are equally toxic. In contrast, A[[beta].sub.1-42] peptides are not toxic to human primary astrocytes, neuronal, and nonneuronal cell lines. Inhibition of de novo protein synthesis protects against A[[beta].sub.1-42] toxicity, indicating that programmed cell death is involved. Bcl-2, Bax-neutralizing antibodies, cDNA expression of a [p53.sup.R273H] dominant negative mutant, and caspase inhibitors prevent A[[beta].sub.1-42]-mediated human neuronal cell death. Taken together, our data directly demonstrate that intracellular A[[beta].sub.1-42] is selectively cytotoxic to human neurons through the p53-Bax cell death pathway.

The SH3 domain is a well characterized small protein module with a simple fold found in many proteins. At acid pH, the SH3 domain (PI3-SH3) of the p85[Alpha] subunit of bovine phosphatidylinositoi 3-kinase slowly forms a gel that consists of typical amyloid fibrils as assessed by electron microscopy, a Congo red binding assay, and x-ray fiber diffraction. The soluble form of PI3-SH3 at acid pH (the A state by a variety of techniques) from Which fibrils are generated has been characterized. Circular dichroism in the far- and near-UV regions and 1H NMR indicate that the A state is substantially unfolded relative to the native protein at neutral pH. NMR diffusion measurements indicate, however, that the effective hydrodynamic radius of the A state is only 23% higher than that of the native protein and is 20% lower than that of the protein denatured in 3.5 M guanidinium chloride. In addition, the A state binds the hydrophobic dye 1-anilinonaphthalene-8-sulfonic acid, which suggests that SH3 in this state has a partially formed hydrophobic core. These results indicate that the A state is partially folded and support the hypothesis that partially folded states formed in solution are precursors of amyloid deposition. Moreover, that this domain aggregates into amyloid fibrils suggests that the potential for amyloid deposition may be a common property of proteins, and not only of a few proteins associated with disease.

Actin filaments in cells are divided by segment 1 domain of gelosin, which is a protein. Segment 1 is a three-layered structure and aids scientists understand how amyloidosis produced by a type of gelsolin originated. Actin domains are joined together by this segment 1 by means of an apolar patch which are surrounded by hydrogen bonds. Better understanding of the behavior of gelsolin is possible with the segment 1 actin acting as an example. With this basic knowledge, the crystal structure of gelsolin can also be traced.

Alzheimer's disease (AD), a neurodegenerative disease, is characterized by the accumulation of amyloid protein (beta protein) which is similar to processes involving ordered protein aggregation. Scrapie, a human prion disease, is characterized by the aggregation of a normal cellular protein, prion protein (Pr P), and is analogous to AD. The transmission of scrapie and the initiation of AD involve the seeding of amyloid formation. AD and prion diseases can be treated by retarding the rate of amyloid formation.

Byline: I. Granier (1), E. Garcia (1), A. Geissler (1), M. D. Boespflug (2), J. Durand-Gasselin (1) Keywords: Key words Postpartum; Cerebral angiopathy; Vasospasm; Ergot derivates; Sumatriptan Abstract: Cerebral angiopathy of the postpartum period is a rare entity, sometimes promoted by vasoconstrictives drug prescription. Its clinical presentation includes headaches, seizures and focal neurological deficits, which develop shortly after a normal pregnancy. The diagnosis is based on clinical findings and angiography, showing multiple narrowing of the intracranial cerebral arteries. This neurological feature is reversible and the clinical outcome is good. We report a case of benign cerebral angiopathy in a 20-year-old woman in the postpartum period, occurring after administration of sumatriptan and ergot derivates. Author Affiliation: (1) Service de Reanimation, Centre Hospitalier Intercommunal Toulon -- La Seyne sur Mer, Font-Pre, 1208 avenue du colonel Picot, BP 1412, F-83056 Toulon Cedex, France Tel. + 33 4 94 61 80 98 Fax + 33 4 94 61 60 54, FR (2) Service de Radiologie, Centre Hospitalier Intercommunal Toulon -- La Seyne sur Mer, Font-Pre, 1208 avenue du colonel Picot, BP 1412, F-83056 Toulon Cedex -- France, FR Article note: Received: 17 August 1998 Final revision received: 25 November 1998 Accepted: 24 February 1999

The effects of heat on the acid-unfolded monomer at pH 2.5 were studied to understand the initial stages in the formation of amyloid fibrils of [beta.sub.2]-microglobulin ([beta]2-m), a protein responsible for dialysis-related amyloidosis. It was found that moderate heat treatment of [beta]2-m in the presence of seed fibrils results in an exothermic sigmoidal transition leading to a conformational state and may be interpreted in terms of the effects of heat associated with the formation, the association and unfolding of fibrils.

A study is conducted on amyloidosis, which is a clinical disorder caused by extra cellular deposition of insoluble abnormal fibrils, derived from aggregation of misfolded, normally soluble, protein. It is seen that though the diagnosis of the disease remains a considerable clinical challenge, specialist centers are having greatly improved outputs for the patients.

Research has been conducted on D18G transthyretin. The authors describe the biophysical properties of this transthyretin, and report that it is an unstable monomeric protein.