ABSTRACT
Staining with Congo Red (CR) is a qualitative method used for the identification of amyloids in vitro and in tissue sections. However, the drawbacks and artefacts obtained when using this dye can be found both in vitro and in vivo Analysis of scientific data from previous studies shows that CR staining alone is not sufficient for confirmation of the amyloid nature of protein aggregates in vitro or for diagnosis of amyloidosis in tissue sections. In the present paper, we describe the characteristics and limitations of other methods used for amyloid studies. Our historical review on the use of CR staining for amyloid studies may provide insight into the pitfalls and caveats related to this technique for researchers considering using this dye.
Subject(s)
Amyloid/analysis , Amyloidosis/diagnosis , Coloring Agents/chemistry , Congo Red/chemistry , Staining and Labeling/methods , Amyloid/history , Amyloidosis/history , Amyloidosis/pathology , Benzothiazoles/chemistry , Benzothiazoles/history , Coloring Agents/history , Congo Red/history , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Immunohistochemistry/history , Immunohistochemistry/methods , Protein Aggregates , Staining and Labeling/historySubject(s)
Amyloid/analysis , Amyloidosis/diagnosis , Coloring Agents/chemistry , Congo Red/chemistry , Amyloid/chemistry , Amyloid/history , Amyloidosis/history , Amyloidosis/pathology , Birefringence , History, 20th Century , History, 21st Century , Humans , Microscopy, Polarization , Staining and Labeling/history , Staining and Labeling/methodsSubject(s)
Humans , Child , Amyloidosis/genetics , Amyloid/history , Hepatomegaly/pathology , Splenomegaly/pathologySubject(s)
Amyloid/history , Amyloidosis/history , Pathology/history , Germany , History, 20th Century , History, 21st Century , HumansABSTRACT
One of the hallmarks of modern science is technically controlled experimentation. In this paper, we underline how technical developments over the last 150 years have repeatedly created new horizons in amyloid research. The main focus is on chemical and biophysical analyses of amyloid fibrils in vivo and in vitro. Investigations into mechanistic aspects of fibril formation and possible links with pathogenesis are also discussed.
Subject(s)
Amyloid/chemistry , Amyloid/history , Research , Amyloid/ultrastructure , Amyloidosis/classification , Amyloidosis/history , Amyloidosis/pathology , Animals , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Protein Structure, SecondaryABSTRACT
On the occasion of the bicentenary of Carl Rokitanskys birth, I was kindly asked to review the relationship between the two great pathologists, Rokitansky and Virchow. As Virchow specialist and editor of the first complete edition of his work, I found the task of writing about their relationship particularly interesting. Although much has written on the subject, I tried to find new points to further illuminate their relationship.
Subject(s)
Amyloid/history , Correspondence as Topic/history , Dissent and Disputes/history , Faculty, Medical/history , Pathology/history , Tuberculosis/history , Typhus, Epidemic Louse-Borne/history , Austria , History, 19th Century , HumansABSTRACT
The first issue of the Archives of Pathology & Laboratory Medicine, published 75 years ago, contained an article by Richard Jaffé on the experimental induction of amyloidosis in mice. This publication was one of a series of milestones that have marked our ongoing and evolving concept of amyloidosis, beginning with the first description by Virchow more than a century ago. Since that time, scientific understanding of amyloidogenesis has expanded through the involvement of newly developed techniques, such as biochemical analysis, electron microscopy, and molecular genetics. As a result of these investigations, it is now known that amyloidoses comprise an entire family of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition. This article seeks to provide a synopsis of the present state of our knowledge with regard to these disorders, including current terminology, classification, major clinical syndromes, and diagnosis.
Subject(s)
Amyloidosis/history , Amyloid/genetics , Amyloid/history , Amyloid/metabolism , Amyloidosis/diagnosis , Amyloidosis/etiology , Animals , History, 19th Century , History, 20th Century , Humans , MiceABSTRACT
Rudolph Virchow, in 1854, introduced and popularized the term amyloid to denote a macroscopic tissue abnormality that exhibited a positive iodine staining reaction. Subsequent light microscopic studies with polarizing optics demonstrated the inherent birefringence of amyloid deposits, a property that increased intensely after staining with Congo red dye. In 1959, electron microscopic examination of ultrathin sections of amyloidotic tissues revealed the presence of fibrils, indeterminate in length and, invariably, 80 to 100 A in width. Using the criteria of Congophilia and fibrillar morphology, 20 or more biochemically distinct forms of amyloid have been identified throughout the animal kingdom; each is specifically associated with a unique clinical syndrome. Fibrils, also 80 to 100 A in width, have been isolated from tissue homogenates using differential sedimentation or solubility. X-ray diffraction analysis revealed the fibrils to be ordered in the beta pleated sheet conformation, with the direction of the polypeptide backbone perpendicular to the fibril axis (cross beta structure). Because of the similar dimensions and tinctorial properties of the fibrils extracted from amyloid-laden tissues and amyloid fibrils in tissue sections, they have been assumed to be identical. However, the spatial relationship of proteoglycans and amyloid P component (AP), common to all forms of amyloid, to the putative protein only fibrils in tissues, has been unclear. Recently, it has been suggested that, in situ, amyloid fibrils are composed of proteoglycans and AP as well as amyloid proteins and thus resemble connective tissue microfibrils. Chemical and physical definition of the fibrils in tissues will be needed to relate the in vitro properties of amyloid protein fibrils to the pathogenesis of amyloid fibril formation in vivo.
Subject(s)
Amyloid/history , Amyloid/chemistry , Amyloid/ultrastructure , Amyloidosis/classification , Amyloidosis/history , Amyloidosis/pathology , Animals , History, 20th Century , Humans , Protein Structure, Secondary , Serum Amyloid A Protein/chemistry , Serum Amyloid A Protein/historyABSTRACT
The presence of amyloid deposits in the pancreas was first described at the beginning of the 20th century. However, it was not until 1987 that the structure of the amylin molecule was identified. Amylin is a 37-amino-acid peptide hormone that is co-secreted with insulin by the pancreatic beta-cells in response to a nutrient stimulus. It is deficient in patients with Type 1 diabetes and elevated in patients in the early stages of Type 2 diabetes, a condition which is characterized by hyperinsulinaemia. Elevation of plasma amylin levels has also been described in patients with impaired glucose tolerance, obese subjects and in pregnant women with both normal glucose tolerance and gestational diabetes mellitus. However, it appears that deficiencies of amylin secretion appear before those of insulin in patients in the later stages of Type 2 diabetes. Early experimental studies suggested that amylin inhibits basal insulin secretion, and induces insulin resistance in skeletal muscle, leading to the hypothesis that it has a role in the aetiology of Type 2 diabetes. However, a number of more recent experimental studies have indicated that amylin is a third active pancreatic islet hormone that works with insulin and glucagon to maintain glucose homeostasis. Amylin appears to regulate glucose inflow to the circulation by influencing the rate of gastric emptying, and thus the rate at which meal-derived glucose enters the system, and also by inhibiting glucose release and hepatic glucose production in the postprandial period.
