Serum Amyloid A (SAA) Proteins.

As normal constituents of blood serum, the Serum Amyloid A (SAA) proteins are small (104 amino acids in humans) and remarkably well-conserved in mammalian evolution. They are synthesized prominently, but not exclusively, in the liver. Fragments of SAA can associate into insoluble fibrils (called "amyloid") characteristic of "secondary" amyloid disease in which they can interrupt normal physiology and lead to organ failure. SAA proteins comprise a family of molecules, two members of which (SAA1 and SAA2) are (along with C-reactive protein, CRP) the most prominent members of the acute phase response (APR) during which their serum levels rise dramatically after trauma, infection and other stimuli. Biologic function (s) of SAA are unresolved but features are consistent with a prominent role in primordial host defense (including the APR ). SAA proteins are lipophilic and contribute to high density lipoproteins (HDL) and cholesterol transport. SAA proteins interact with specific receptors and have been implicated in tissue remodeling through metalloproteinases, local tissue changes in atherosclerosis, cancer metastasis, lung inflammation, maternal-fetal health and intestinal physiology. Molecular details of some of these are emerging.

Serum amyloid A - a review.

Serum amyloid A (SAA) proteins were isolated and named over 50 years ago. They are small (104 amino acids) and have a striking relationship to the acute phase response with serum levels rising as much as 1000-fold in 24 hours. SAA proteins are encoded in a family of closely-related genes and have been remarkably conserved throughout vertebrate evolution. Amino-terminal fragments of SAA can form highly organized, insoluble fibrils that accumulate in "secondary" amyloid disease. Despite their evolutionary preservation and dynamic synthesis pattern SAA proteins have lacked well-defined physiologic roles. However, considering an array of many, often unrelated, reports now permits a more coordinated perspective. Protein studies have elucidated basic SAA structure and fibril formation. Appreciating SAA's lipophilicity helps relate it to lipid transport and metabolism as well as atherosclerosis. SAA's function as a cytokine-like protein has become recognized in cell-cell communication as well as feedback in inflammatory, immunologic, neoplastic and protective pathways. SAA likely has a critical role in control and possibly propagation of the primordial acute phase response. Appreciating the many cellular and molecular interactions for SAA suggests possibilities for improved understanding of pathophysiology as well as treatment and disease prevention.

Serum amyloid A1 (SAA1) protein in human colostrum.

Proteins of the serum amyloid A (SAA) family have been remarkably conserved in evolution. Their biologic function(s) are not fully defined but they are likely to be a part of primordial host defense. We have detected a ∼ 12-kDa protein reacting with antibodies against serum amyloid A (SAA) in human colostrum by western blotting. Mass spectrometry identified the reactive species as SAA1, previously identified as a prominent member of the acute-phase response in serum. Our finding SAA1 in human colostrum contrasts with bovine, caprine and ovine colostrum where a species corresponding to putative SAA3 is uniformly present. SAA1 protein in human colostrum presumably contributes to neonatal protection.

Introduction to the mini-review series on mitochondrial matters in epilepsy.

Dysfunction of neuronal metabolism is central to all forms of seizure activity. Clinical, genetic and metabolic studies have implicated mitochondria in the process. Alterations in electron transport, generation of reactive oxygen species, calcium metabolism and apoptosis all have been described in human and animal nervous tissue and reflect changes in mitochondrial physiology. Improved understanding of the molecular details underlying seizures has begun to provide rational approaches to the design of new treatment strategies.

Mitochondrial matters in Huntington disease.

Huntington Disease (HD) is a relatively common inherited neuropathy with characteristic cognitive and behavioral features. HD usually has a late onset and often is not recognized until the third or fourth decades of life. Transmitted as an autosomal dominant trait, HD has become a prototype for understanding a group of neurogenetic disorders. As a class, HD and the others are manifestations of the expansion of a trinucleotide repeat within the gene coding or structural region. In HD expansion of the (CAG)(n) repeat in the first exon from an average of 18 (normal) to a median of 44 is the underlying molecular biologic change. In affected individuals, the mutant HD protein (Huntingtin, mHtt) thus contains an extended polyglutamine repeat. Clinical and neuropathic changes in the caudate and putamen nuclei occur relatively early with other brain regions being affected later. Mitochondrial structure, altered electron transport and increased brain lactate levels have implicated mitochondria in HD pathophysiology. There is also evidence that reduced transcription of the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1 alpha) leads to altered downstream gene regulation. Further evidence for mitochondrial involvement is presented in the following reviews. Clarifying mitochondrial derangements has led to some possibilities for therapeutic intervention.

Mitochondrial matters in Parkinson disease: introduction.

Individuals with Parkinson disease (PD) are encountered frequently and have progressively severe neurologic changes. The central nervous system changes involve dopaminergic neurons in the basal ganglia and substantia nigra. Although usually sporadic, rare forms of PD are familial and the responsible genes have been identified. These genes affect mitochondrial function and can be studied in animals. Brains of affected animals reveal consequences of reactive oxygen species (ROS)--quinones, dopamine oxidation products, tyrosine nitration, lipid peroxidation and amino-aldehyde adducts. The three genes are important for maintaining physical and functional mitochondrial integrity. The cumulative effects of mitochondrial dysfunction, particularly those mediated by ROS, ultimately lead to at least some of the clinical and pathologic changes of PD.

Comprehensive outpatient health assessment: a case-finding tool in 500 consecutive asymptomatic individuals.

This study appraises the case-finding efficiency of a single-day outpatient program of a broad-based clinical evaluation and laboratory studies in asymptomatic adults. The same protocol, varied only according to age and sex, was used for 500 individuals encountered consecutively over 15 months, and an unanticipated new diagnosis or important clinical or laboratory finding was established for one-third of them. The diagnoses varied widely, consistent with the breadth of the observations, and most led to specific recommendations for care. These findings confirm the case-finding efficacy of comprehensive clinical assessments supported by basic laboratory studies and counter the notion that specific tests and/or portions of the review of systems and physical examination can be eliminated in establishing a reliable medical database for asymptomatic adults. In addition, such comprehensive data provide essential reference material for later comparisons.