HIGH-RESOLUTION ELECTRON MICROSCOPIC ANALYSIS OF THE AMYLOID FIBRIL

The ultrastructural organization of the fibrous component of amyloid has been analyzed by means of high resolution electron microscopy of negatively stained isolated amyloid fibrils and of positively stained amyloid fibrils in thin tissue sections. It was found that a number of subunits could be resolved according to their dimensions. The following structural organization is proposed. The amyloid fibril, the fibrous component of amyloid as seen in electron microscopy of thin tissue sections, consists of a number of filaments aggregated side-by-side. These amyloid filaments are approximately 75–80 A in diameter and consist of five (or less likely six) subunits (amyloid protofibrils) which are arranged parallel to each other, longitudinal or slightly oblique to the long axis of the filament. The filament has often seemed to disperse into several longitudinal rows. The amyloid protofibril is about 25–35 A wide and appears to consist of two or three subunit strands helically arranged with a 35–50-A repeat (or, less likely, is composed of globular subunits aggregated end-to-end). These amyloid subprotofibrillar strands measure approximately 10–15 A in diameter.

[1]  B. Olsen Electron microscope studies on collagen. IV. Structure of vitrosin fibrils and interaction properties of vitrosin molecules. , 1967, Journal of ultrastructure research.

[2]  A. Cohen,et al.  The lipid content of amyloid fibrils purified by a variety of methods. , 1967, The American journal of pathology.

[3]  A. Cohen,et al.  A CONGO RED STAINING METHOD FOR EPOXY-EMBEDDED AMYLOID , 1966, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[4]  A. Heyn,et al.  THE MICROCRYSTALLINE STRUCTURE OF CELLULOSE IN CELL WALLS OF COTTON, RAMIE, AND JUTE FIBERS AS REVEALED BY NEGATIVE STAINING OF SECTIONS , 1966, The Journal of cell biology.

[5]  E. van Bruggen,et al.  Physical properties of a DNA-dependent RNA polymerase from Escherichia coli. , 1966, Journal of molecular biology.

[6]  G. Glenner,et al.  The ultrastructure of human amyloid as revealed by the negative staining technique. , 1966, Journal of ultrastructure research.

[7]  Y. Mochizuki,et al.  THE NUCLEOIDS OF RAT LIVER CELL MICROBODIES , 1966, The Journal of cell biology.

[8]  Yutaka Kikkawa,et al.  NEW FEATURES OF AMYLOID FOUND AFTER DIGESTION WITH TRYPSIN , 1966, The Journal of cell biology.

[9]  A. Cohen,et al.  The Relation Between Isolated Human Amyloid Fibrils and Human γ-Globulin and Its Subunits , 1966, The Journal of Immunology.

[10]  N. Eriksen,et al.  Amyloid. 3. A protein related to the subunit structure of human amyloid fibrils. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Dobb The structure of keratin protofibrils. , 1966, Journal of ultrastructure research.

[12]  H. Puchtler,et al.  Demonstration of amyloid with direct cotton dyes. Experiences with a new method for the selective staining of amyloid by sirius red F3BA and sirius supra scarlet GG-CF. , 1965, Archives of pathology.

[13]  L. Ruinen,et al.  Electron microscopic studies on the fibrillar component of human splenic amyloid. , 1965, The Journal of laboratory and clinical medicine.

[14]  A. Cohen,et al.  The light and electron microscopic autoradiographic demonstration of local amyloid formation in spleen explants. , 1965, The American journal of pathology.

[15]  J. Moskal,et al.  Prostatic corpora amylacea. A study with the electron microscope and electron probe. , 1965, Archives of pathology.

[16]  J. Lowy Structure of the proximal ends of bacterial flagella. , 1965, Journal of molecular biology.

[17]  M. Glimcher,et al.  The solubilization and reconstitution of bone collagen. , 1965, Journal of ultrastructure research.

[18]  A. Cohen,et al.  IMMUNOLOGIC STUDIES ON A PROTEIN EXTRACTED FROM HUMAN SECONDARY AMYLOID. , 1965, The New England journal of medicine.

[19]  A. Cohen,et al.  Solubility characteristics of isolated amyloid fibrils. , 1965, Biochimica et biophysica acta.

[20]  A. Cohen,et al.  Structure of Amyloid Fibrils after Negative Staining and High-resolution Electron Microscopy , 1965, Nature.

[21]  H. Micklem,et al.  AMYLOIDOSIS AND LYMPHOID APLASIA IN MOUSE RADIATION CHIMERAS. , 1965, The American journal of pathology.

[22]  J. Luft,et al.  THE INFLUENCE OF BUFFER SYSTEMS ON FIXATION WITH OSMIUM TETROXIDE. , 1965, Journal of ultrastructure research.

[23]  J. Lowy,et al.  ELECTRON MICROSCOPE STUDIES OF BACTERIAL FLAGELLA. , 1965, Journal of molecular biology.

[24]  D. J. Johnson,et al.  Alpha-Keratin: Ultrafine Structure of α-Keratin , 1965, Nature.

[25]  Z. Hruban,et al.  Uricase: Localization in Hepatic Microbodies , 1964, Science.

[26]  R. Manley Fine Structure of Native Cellulose Microfibrils , 1964, Nature.

[27]  H. Puchtler,et al.  ON THE BINDING OF DIRECT COTTON DYES BY AMYLOID , 1964, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[28]  P. Hofschneider,et al.  PREPARATION AND PROPERTIES OF RNA-POLYMERASE PARTICLES. , 1964, Journal of molecular biology.

[29]  T. Shimamura,et al.  EXPERIMENTAL AMYLOIDOSIS. 3. LIGHT AND ELECTRON MICROSCOPIC OBSERVATIONS OF RENAL GLOMERULI. , 1964, Laboratory investigation; a journal of technical methods and pathology.

[30]  R. Fraser,et al.  The coiled-coil model of α-keratin structure , 1964 .

[31]  D. Abram,et al.  IN VITRO FORMATION OF FLAGELLA-LIKE FILAMENTS AND OTHER STRUCTURES FROM FLAGELLIN. , 1964, Journal of molecular biology.

[32]  D. E. Green,et al.  A MACROMOLECULAR REPEATING UNIT OF MITOCHONDRIAL STRUCTURE AND FUNCTION , 1964, The Journal of cell biology.

[33]  A. Cohen,et al.  THE ISOLATION OF AMYLOID FIBRILS AND A STUDY OF THE EFFECT OF COLLAGENASE AND HYALURONIDASE , 1964, The Journal of cell biology.

[34]  M. Dobb Fine Structure of Keratin , 1964, Nature.

[35]  G. Sorenson,et al.  Experimental Amyloidosis: II. Light and Electron Microscopic Observations of Liver , 1964 .

[36]  R. Terry,et al.  ULTRASTRUCTURAL STUDIES IN ALZHEIMER'S PRESENILE DEMENTIA. , 1964, The American journal of pathology.

[37]  F. S. Sjoestrand A NEW ULTRASTRUCTURAL ELEMENT OF THE MEMBRANES IN MITOCHONDRIA AND OF SOME CYTOPLASMIC MEMBRANES. , 1963, Journal of ultrastructure research.

[38]  J. Churg,et al.  The Mesangium of the Renal Glomerulus: Electron Microscopic Studies of Pathologic Alterations. , 1963, The American journal of pathology.

[39]  H. Huxley,et al.  ELECTRON MICROSCOPE STUDIES ON THE STRUCTURE OF NATURAL AND SYNTHETIC PROTEIN FILAMENTS FROM STRIATED MUSCLE. , 1963, Journal of molecular biology.

[40]  D. Kerridge,et al.  THE FINE STRUCTURE AND MODE OF ATTACHMENT OF THE SHEATHED FLAGELLUM OF VIBRIO METCHNIKOVII , 1963, The Journal of cell biology.

[41]  R. P. Peterson A NOTE ON THE STRUCTURE OF CRAYFISH MYOFILAMENTS , 1963, The Journal of cell biology.

[42]  F. Sjöstrand The ultrastructure of the plasma membrane of columnar epithelium cells of the mouse intestine , 1963 .

[43]  R. Markham,et al.  Methods for the enhancement of image detail and accentuation of structure in electron microscopy , 1963 .

[44]  D. Danon,et al.  THE USE OF SHADOW-CASTING TECHNIQUE FOR MEASUREMENT OF THE WIDTH OF ELONGATED PARTICLES , 1963, The Journal of cell biology.

[45]  L. Gotte,et al.  Electron microscope observations on the structure of elastin. , 1963, Journal of atherosclerosis research.

[46]  Russell J. Barrnett,et al.  Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation. , 1963 .

[47]  E. Reynolds THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY , 1963, The Journal of cell biology.

[48]  A. Bangham,et al.  Action of Saponin on Biological Cell Membranes , 1962, Nature.

[49]  A. Frensdorff,et al.  A study of the fine structure of the amyloid associated with familial Mediterranean fever. , 1962, The American journal of pathology.

[50]  Sorenson Gd,et al.  Experimental amyloidosis. I. Light and electron microscopic observation of spleen and lymph nodes. , 1962 .

[51]  R. Dourmashkin,et al.  Electron Microscopic Observations on Rous Sarcoma Virus and Cell Membranes , 1962, Nature.

[52]  H. Puchtler,et al.  ON THE BINDING OF CONGO RED BY AMYLOID , 1962 .

[53]  D. Kerridge,et al.  Structural components of flagella from Salmonella typhimurium. , 1962, Journal of molecular biology.

[54]  R. Fraser,et al.  Molecular Organization in Alpha-Keratin , 1962, Nature.

[55]  B. Filshie,et al.  The fine structure of a-keratin , 1961 .

[56]  R. Fraser,et al.  The molecular configuration of α-keratin , 1961 .

[57]  F. Fitch Histological Techniques for Electron Microscopy , 1961 .

[58]  John H. Luft,et al.  IMPROVEMENTS IN EPOXY RESIN EMBEDDING METHODS , 1961, The Journal of biophysical and biochemical cytology.

[59]  E. Letterer,et al.  Studien zur elektronenoptischen und immunmorphologischen Struktur des Amyloids1 , 1960 .

[60]  L. Weiss,et al.  Electron microscopic observations of the spleen during the induction of experimental amyloidosis in the rabbit. , 1960, The American journal of pathology.

[61]  A. Crivellaro,et al.  A STUDY OF THE FINE STRUCTURE OF THE KIDNEY IN CASEIN-INDUCED AMYLOIDOSIS IN RABBITS , 1960, The Journal of experimental medicine.

[62]  Movat Hz The fine structure of the glomerulus in amyloidosis. , 1960 .

[63]  C. Levene,et al.  Studies on experimental amyloidosis. I. Analysis of histology and staining reactions of casein-induced amyloidosis in the rabbit. , 1959, The American journal of pathology.

[64]  A. Cohen,et al.  Electron Microscopic Observations on a Fibrous Component in Amyloid of Diverse Origins , 1959, Nature.

[65]  G. Rogers Electron microscopy of wool. , 1959, Journal of ultrastructure research.

[66]  M. L. Watson Staining of Tissue Sections for Electron Microscopy with Heavy Metals , 1958, The Journal of biophysical and biochemical cytology.

[67]  H. Fernández-morán,et al.  ELECTRON MICROSCOPE AND LOW-ANGLE X-RAY DIFFRACTION STUDIES OF THE NERVE MYELIN SHEATH , 1957, The Journal of biophysical and biochemical cytology.

[68]  G. Romhányi Über die submikroskopische Struktur des Amyloids , 1949 .

[69]  R. Reed,et al.  An Electron Microscope Study of Cellulose in the Wall of Valonia Ventricosa , 1948, Nature.

[70]  P. Ladewig Double-Refringence of the Amyloid-Congo-Red-Complex in Histological Sections , 1945, Nature.

[71]  D. R. Morey Dichroism of Dyed Fibres as a Means of Studying Micellar Arrangement , 1934 .

[72]  A. Cohen Preliminary chemical analysis of partially purified amyloid fibrils. , 1966, American journal of pharmacy and the sciences supporting public health.

[73]  Cohen As Preliminary chemical analysis of partially purified amyloid fibrils. , 1966 .

[74]  A. Cohen The constitution and genesis of amyloid. , 1965, International review of experimental pathology.

[75]  Cohen As The constitution and genesis of amyloid. , 1965 .

[76]  A. Bangham,et al.  NEGATIVE STAINING OF PHOSPHOLIPIDS AND THEIR STRUCTURAL MODIFICATION BY SURFACE-ACTIVE AGENTS AS OBSERVED IN THE ELECTRON MICROSCOPE. , 1964, Journal of molecular biology.

[77]  J. Lucy,et al.  STRUCTURE AND ASSEMBLY OF MACROMOLECULAR LIPID COMPLEXES COMPOSED OF GLOBULAR MICELLES. , 1964, Journal of molecular biology.

[78]  C. Grey,et al.  THE AMYLOID IN SOLID CARCINOMA OF THE THYROID GLAND. STAINING CHARACTERISTICS, TISSUE CULTURE, AND ELECTRON MICROSCOPIC OBSERVATIONS. , 1964, Laboratory investigation; a journal of technical methods and pathology.

[79]  J. Lowy,et al.  The structure of F-actin and of actin filaments isolated from muscle , 1963 .

[80]  A. Bangham PHYSICAL STRUCTURE AND BEHAVIOR OF LIPIDS AND LIPID ENZYMES. , 1963, Advances in lipid research.

[81]  河瀬 収 Electron microscopic ultrastructure of the elastic fiber in arteriosclerosis , 1963 .

[82]  B. Filshie,et al.  Some Aspects of the Ultrastructure of α-Keratin, Bacterial Flagella, and Feather Keratin , 1963 .

[83]  Bangham Ad PHYSICAL STRUCTURE AND BEHAVIOR OF LIPIDS AND LIPID ENZYMES. , 1963 .

[84]  J. Lucy,et al.  Action of Saponin on Biological Cell Membranes , 1962, Nature.

[85]  G. Sorenson,et al.  Experimental amyloidosis. I. Light and electron microscopic observation of spleen and lymph nodes. , 1962, Laboratory investigation; a journal of technical methods and pathology.

[86]  H. Fernández-morán NEW APPROACHES IN THE STUDY OF BIOLOGICAL ULTRASTRUCTURE BY HIGH-RESOLUTION ELECTRON MICROSCOPY , 1962 .

[87]  B. Afzelius CHEMICAL FIXATIVES FOR ELECTRON MICROSCOPY , 1962 .

[88]  R. Valentine,et al.  AN ASSESSMENT OF NEGATIVE STAINING TECHNIQUES FOR REVEALING ULTRASTRUCTURE , 1962 .

[89]  F. Sjöstrand CRITICAL EVALUATION OF ULTRASTRUCTURAL PATTERNS WITH RESPECT TO FIXATION11This investigation was supported in part by Research Grant B-2889, National Advisory Neurological Diseases and Blindness Council, Public Health Service, and in part by Research Grant G-15048 of the National Science Foundation. , 1962 .

[90]  R. Preston THE ELECTRON MICROSCOPY AND ELECTRON DIFFRACTION ANALYSIS OF NATURAL CELLULOSE , 1962 .

[91]  R. Burge QUANTITATIVE ELECTRON MICROSCOPY , 1962 .

[92]  Robert T. Harris,et al.  The interpretation of ultrastructure , 1962 .

[93]  R. Caesar Elektronenmikroskopische Untersuchungen an menschlichem Amyloid bei verschiedenen Grundkrankheiten , 1961 .

[94]  宇宿 源太郎 Electronmicroscopical studies on the ultrastructure of the elastic fiber , 1960 .

[95]  H. Movat,et al.  The fine structure of the glomerulus in amyloidosis. , 1960, Archives of pathology.

[96]  R. Horne,et al.  A negative staining method for high resolution electron microscopy of viruses. , 1959, Biochimica et biophysica acta.

[97]  F. S. Sjostrand A method to improve contrast in high resolution electron microscopy of ultrathin tissue sections. , 1956, Experimental cell research.

[98]  B. R. Forker,et al.  Metachromasy of amyloid; a spectrophotometric study with particular reference to the dye-chromotrope bond. , 1956, Laboratory investigation; a journal of technical methods and pathology.

[99]  Carnes Wh,et al.  Metachromasy of amyloid; a spectrophotometric study with particular reference to the dye-chromotrope bond. , 1956 .

[100]  H. Pfeiffer Messungen der doppelbrechung (Δn) und des dichroismus (Δk) am amyloid in kulturen in vitro , 1953 .

[101]  B. Filshie,et al.  A N E L E C T R O N , 2022 .