Garamycin* Injectable TM/TV GARAMYCIN Injectable (40 mg (base)Iml) GARAMYCIN Pediatric Injectable (10 mg (base)/mI) INDICATIONS: GARAMYCIN is indicated in the treatment of serious infections caused by proven susceptible organisms. In suspected or documented gram-negative septicemia, parficularly when shock or hypotension are present, GARAMYCIN should be considered for initial antimicrobial therapy. In staphylococcal infections. GARAMYCIN should be considered when conventional antimicrobial therapy is inappropriate or when susceptibility testing and clinical judgment indicate its use. ADMINISTRATION AND DOSAGE: INTRAMUSCULAR/INTRAVENOUSttADMINISTRATION: A. Urinary Tract Infections: The usual dosage in lower urinary tract infections is 0.8-1.2 mg/kg/day in Iwo or three equally divided doses for seven to ten days. For increased antibacterial activity it may be advantageous to alkal inize the urine. Infections of the upper urinary tract, such as pyelonephritis, should be treated according to one 01 the schedules for systemic infections. B. Systemic Infections -Normal Renal Function: The treatment of systemic infections in patients with normal renal function requires a dosage of 3 mg/kg/day in the three equally divided doses. A course of seven to ten days of treatment will usually clear an infection due to a susceptible organism. In patients with lifethreatening infections, dosages up to 5 mg/kg/day should be administered in three or four equally divided doses. This dosage should be reduced to 3 mg/kg/day as soon as clinically indicated. C. Patients with Impaired Renal Function: In patients with diminished renal function or those undergoing intermittant hemodialysis, the dosage has to be adjusted depending on the degree of renal impairment. For detailed information consult the product monograph or the Schering Representative. ttINTRA VENOUS ADMINISTRATION: The usual effective dosage of GARAMYCIN Injectable administered intravenously is 3 mg/kg/day in three equally divided doses. For intravenous administration, a single dose (1 mg/ kg) of GARAMYCIN Injectable is diluted in 100-200 ml of sterile normal saline or 5% dextrose. The solution is infused over a period of one to two hours and repeated two to three times a day. The usual duration of treatment is seven to ten days. PRECAUTIONS: Ototoxicity: Gentamicin, like other aminoglycosides, has produced ototoxicity in experimental animals and man. It is manifested by damage to vestibular function and may be delayed in onset. Damage has occurred in patients who were uremic, had renal dysfunction, had prior therapy with ototoxic drugs or received higher doses or longer therapy than those recommended. The concomitant use of ethacrynic acid and furosemide should be avoided. The physician should strongly consider discontinuing the drug if the patient complains of tinnitus, dizziness or loss of hearing. Serum GARAMYCIN levels in excess of 12 pg/mI should be avoided. Nephrotoxicity: Nephrotoxicity manifested by an elevated BUN or serum creatinine level or a decrease in the creatinine clearance has been reported with GARAMYCIN. In most cases these changes have been reversible. Neuromuscular Blocking Action: Neuromuscular blockage and respiratory paralysis have been reported in animals. The possibility of this occurring in man should be kept in mind particularly in those patients receiving neuromuscular blocking agents. ADVERSE REACTIONS: Among other adverse reactions reported infrequently and possibly related to GARAMYCIN are elevated SOOT, increased serum bilirubin, granulocytopenia and urticaria. Reactions reported rarely and possibly related to GARAMYCIN include drug fever, hypotension, hypertension, itching, hepatomegaly and splenomegaly. OVERDOSAGE: Peritoneal or hemodialysis will aid in the removal of GARAMYCIN from the blood. SUPPLIED: Each ml of aqueous parenteral solution at pH 4.5 contains: 40 mg or 10 mg (pediatric) of gentamicin base. Preservatives, methylparaben U.S.P., propylparaben U.SP., sodium bisulfite U.S.P., disodium edetate U.S.P. Available in 2 ml multipledose vials and 1.5 ml Unidose* ampoules containing 60 mg gentamicin base/1.5 ml. Also available in 2 ml and 1.5 ml pre-filled disposable syringes containing 40 mg gentamicin base per ml. Solutions are heat stable and do not require refrigeration. Product monograph available on request from Schering Corporation Limited Pointe Claire, Quebec. H9R 1B4
MEMBER
*Reg TM.
Newer concepts in amyloidogenesis Important advances in our understanding of amyloidosis have been made as a result of studies of amyloid fibrils. These studies have shown that there are two major types of amyloid-fibril proteins - one related to immunoglobulins and the other not related. Direct proof of the immunoglobulin origin of amyloid was obtained from peptide mapping and analysis of the sequence of amino acids in a solution of amyloid fibrils from patients with primary amyloidosis, plasma-cell dyscrasia, localized nodular pulmonary amyloidosis and secondary amyloidosis. The major protein constituent of the amyloid fibril was homologous with the variable region of K or X light chains or the intact light chain, or both.1 Confirmatory evidence was obtained by the finding that antisera to K-type amyloid-fibril proteins gave reactions of partial identity with most Bence Jones K proteins tested but not with X proteins. Conversely, an antiserum to a X-type fibril protein reacted with other X fibril proteins and with some X Bence Jones proteins but not with K fibril proteins or K Bence Jones proteins.1 Thus, the antisera were either reacting with antigenic determinants located in the variable regions of light chains or detecting conformational antigens, since the reactivity was abolished by total reduction and alkylation of the fibrils.' Amyloid-like substances have been produced in vitro by peptic digestion of some purified Bence Jones proteins, particularly of the Vxi subtype.3 Recently the production of an amyloid-like substance from a heavy-chain-disease protein has been reported.4 Husby, Natvig and Sletten3 described a protein consisting of a single polypeptide chain of approximately 100 amino acids, which was the major constituent of amyloid-fibril proteins from a patient with primary amyloidosis. Aminoacid-sequence analysis showed some homology with the N-terminal aminoacid sequence of X Bence Jones protein and it was suggested that this protein represented a new subtype. Antisera to protein from this patient did not react with any other amyloid preparation or with immunoglobulins or their chains or fragments. The patient's serum contained a protein antigenically related to the amyloid-fibril protein. This serum component was also detected in 5% of sera with M components, whereas a predominance of X light chains was seen among the sera with monoclonal IgG or IgA.6
872 CMA JOURNAL/MAY 22, 1976/VOL. 114
Unlike amyloid fibrils in primary amyloidosis or plasma-cell dyscrasia, the major component of amyloid fibrils in most cases of secondary amyloidosis, as well as in familial Mediterranean fever, is a nonimmunoglobulin protein, AA, * originally described by Benditt and colleagues.7 It consists of 76 amino acids and has a molecular weight of from 7000 to 9000 daltons.8 Husby and associates9 demonstrated this protein in some amyloid fibrils from patients with primary amyloidosis and plasma-cell dyscrasia. Also, the void volume material of secondary amyloid preparations chromatographed on Sephadex G-100 was shown by peptide mapping to be heterogeneous and was believed to be derived from immunoglobulin light chains.'0 It appears, therefore, that amyloid preparations from some patients with primary amyloidosis, myeloma, macroglobulinemia and secondary amyloidosis have common constituents of both immunoglobulin and nonimmunoglobulin origin. This may explain the cross-reactivity observed in gel diffusion between antisera against secondary amyloid and some amyloid preparations from patients with primary amyloidosis and plasma-cell dyscrasia. A serum component, SAA, * antigenically related to the nonimmunoglobulin protein AA, with a-fl electrophoretic mobility and a molecular weight of 100 000, has been demonstrated.1' SAA, which may be a circulating precursor of amyloid fibrils, was detected in serum of patients with all clinical types of amyloidosis as well as in hypogammaglobulinemic serum. SAA was also found in normal adult and cord serum. Its concentration increases with age, pregnancy, tuberculous infection, rheumatoid arthritis, acute infectious disease, biliary cirrhosis, lymphoma, myeloma, macroglobulinemia, carcinoma and all types of amyloidosis.'2 In addition to the fibrillary component, amyloid deposits contain small quantities of a glycoprotein that possesses antigenic identity with a constituent of normal plasma, the P component. It is composed of five globular subunits and has a pentagonal structure. Its molecular weight is approximately 180 000. Initial analysis of the first 23 amino acid residues showed that their sequence differed from all protein sequences known.'3 However, P component of amyloid has since been found to be similar to CiT, a subcomponent *Termmology adopted at International Symposium on Amyloidosis, Helsinki, 1974.
of the first component of complement.'7 Recently the amino acid sequence of amyloid fibrils from medullary carcinoma of the thyroid has been found to be similar to that of calcitonin,'8 and amyloid-like material has been produced in vitro by proteolytic digestion of insulin and glucagon.'9 Despite the impressive advances in our knowledge of the immunochemistry of amyloid, the precise mechanism or mechanisms involved in human amyloidogenesis is not known. In amyloid of immunoglobulin origin and in plasma-cell dyscrasia with amyloid, X light chains predominate, which is the reverse of what is found in plasma-cell dyscrasias not associated with amyloid and in normal immunoglobulins. Also, amyloid fibrils are more readily produced in vitro by peptic digestion of X-type Bence Jones proteins than of K-type proteins;14 this suggests that an amyloidogenic structure is inherent in X light chains. Glenner, Terry and Isersky' have postulated intralysosomal proteolytic digestion of light chains by macrophages as a possible mechanism for amyloid formation. Peptic digestion studies in vitro also have shown that amyloid fibrils originate in similar fragments at an acid pH. Electron microscopy has demonstrated the intracellular localization of amyloid in macrophages." However, in several cases the intact light chain, not its fragments, has been found to be the major component of the amyloid-fibril protein, so that other mechanisms must be considered as well. It has been suggested that light-chain polymers of high molecular weight, which have been reported in serum in several cases associated with amyloidosis, may predispose to the development of amyloid.' It was postulated that such polymers may be precipitated from serum and digested by intracellular lysosomal enzymes of macrophages.' In this regard, we were unable to produce typical amyloid fibrils in vitro by peptic digestion of the purified Bence Jones tetramer of X type from one of the above cases or by digestion of two other purified Bence Jones tetramers of K type. The possibility that light chains and Bence Jones proteins may have antibody activity through the formation of disulfide-linked light-chain dimers has also been proposed.1 The similarity of these dimers to Fab (antigen-binding) fragments provides a theoretical basis for antigen binding.' Serum protein SAA, of high molecular weight, which is believed to be the precursor of the nonimmunoglobulin protein AA and is found in normal serum as well as in all types of amyl-
oidosis, may interact with light chains to form amyloid. In summary, amyloid has a heterogeneous composition, which may be primarily of immunoglobulin or nonimmunoglobulin origin. Normal constituents of plasma antigenically related to amyloid proteins have been identified and are believed to be circulating precursors of amyloid. The relative importance of these plasma factors, as opposed to local factors, and the way in which they interact in amyloid formation remain to be elucidated.
ferent proteins related to ai.Iyloid fibrils. Scand J immunol 3: 391, 1974
7. BEr.rs-r EP, ERIK5EN N, HERMOOSON MA, Ct
8. 9.
10. II.
al: The major proteins of human and monkey amyloid substance: common properties including unusual N-terminal amino-acid sequences. FEBS Lett 19: 169, 1971 SLEl-FEN K, HussY G: The complete aminoacid sequence of non-immunoglobulin amyloid fibril protein AS in juvenile rheumatoid arthritis. Eur I Biochem 41: 117 1974 HUsBY G, SLElTEN K, MIcHAaLss.N TE, et ak Amyloid fibril protein subunit, 'protein AS': distribution in tissue and serum in different clinical types of amyloidosis including that associated with myelomatosis and Waldenstrom's macroglobulinaemia. Scand I Immuno! 2: 395, 1973 LEVIN M, FRANKLIN EC, FRANGIONE B, et al: The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. I Clin Invest 51: 2773, 1972 Hussy G, NATYIG JB: A serum component
related to nonimmunoglobulin amyloid protein AS. a possible precursor of the fibrils.
ALLAN KATZ, MD
Associate professor Department of pathology University of Toronto Toronto, ON
I Clin Invest 53: 1054, 1974 12. ROSENTHAL CI, FRANKLIN EC: Variation with age and disease of an amyloid A proteinrelated serum component. I Clin invest 55:
746, 1975 13. SKINNER M, COHEN AS, SHIRAHAMA T, et al: P-component (pentagonal unit) of amyloid: isolation, characterization, and sequence anal-
W. PRUZANSKI, MD, FRCP[C], FACP
Head, division of immunology Wellesley Hospital Toronto, ON
ysis. I Lab Clin Med 84: 604, 1974 D FRANKLIN EC: Morphologic, chemical, and immunologic studies of amyloid-like fibrils formed from Bence Jones proteins by proteolysis. I Immunol 111: 10, 1973
14. LINKE RP, ZUCKER-FRANKLIN
References 1. GLENNER GG, Tasutv WD, IsERsKY C: Amyloidosis: its nature and pathogenesis. Semin Hematol 10: 65, 1973
15. ZUCKER-FRANKLIN D, FRANKLIN EC: Intracellular localization of human amyloid by fluorescence and electron microscopy. Am /
2. FRANKLIN EC, ZUCKER-FRANKLIN D: Antisera specific for human amyloid reactive with
Pathol 59: 23, 1970 16. DORRINOTON XI, TANFORD C: Molecular size and conformation of immunoglobulins. Adv ImmunoL 12: 233, 1970
conformational antigens. Proc Soc Exp Biol Med 140: 565, 1972
3. GLENNER GG, EIN D, EANES ED, et al: Creation of "amyloid" fibrils from Bence
17. PAINTER RH, PINTERIc L, HOFMANN T, et al:
Jones proteins in vitro. Science 174: 712, 1971
Ultrastructure and chemistry of CIT, subcomponent of Cl: similarity to amyloid Pcomponent. I Immunol (in press) 18. SLETTEN K, WESTERMARK P, NATVIG JD: Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. I Exp Med 143: 993, 1976
4. PRUZANSKI W, KATZ A, NYBERO SC, et at: In vitro production of an amyloid-like substance from gamma 3 heavy chain disease
protein. Immunol Commun 3: 469, 1974 5. HUSBY G, NATVIG JB, SLEITEN K: New third class of amyloid fibril protein. J Exp Med 139: 773, 1974
19. GLENNER GG, EANES ED, BLADEN HA, Ct al: .3-pleated sheet fibrils. A comparison of
6. HUSSY G, NATYIG JB, HARBOE M: The occurrence in sera with M-components of dif-
native amyloid with synthetic protein fibrils. I Histochem Cytochem 22: 1141, 1974
II I. g
ii' I * II I I. I I.' S
S
0
0
*
A
*g.
.
A *
* S
*gg * S
S
9
0 .0. .S . S .
S S
S S
* *
*.
*.
S *.S
S
S A
... 0 S
I
S
* *
S
*, * U gA *gA
*.
A
A
S..
'@.
S
CMA JOURNAL/MAY 22, 1976/VOL. 114 873
MEMBER
*Reg TM.
Newer concepts in amyloidogenesis Important advances in our understanding of amyloidosis have been made as a result of studies of amyloid fibrils. These studies have shown that there are two major types of amyloid-fibril proteins - one related to immunoglobulins and the other not related. Direct proof of the immunoglobulin origin of amyloid was obtained from peptide mapping and analysis of the sequence of amino acids in a solution of amyloid fibrils from patients with primary amyloidosis, plasma-cell dyscrasia, localized nodular pulmonary amyloidosis and secondary amyloidosis. The major protein constituent of the amyloid fibril was homologous with the variable region of K or X light chains or the intact light chain, or both.1 Confirmatory evidence was obtained by the finding that antisera to K-type amyloid-fibril proteins gave reactions of partial identity with most Bence Jones K proteins tested but not with X proteins. Conversely, an antiserum to a X-type fibril protein reacted with other X fibril proteins and with some X Bence Jones proteins but not with K fibril proteins or K Bence Jones proteins.1 Thus, the antisera were either reacting with antigenic determinants located in the variable regions of light chains or detecting conformational antigens, since the reactivity was abolished by total reduction and alkylation of the fibrils.' Amyloid-like substances have been produced in vitro by peptic digestion of some purified Bence Jones proteins, particularly of the Vxi subtype.3 Recently the production of an amyloid-like substance from a heavy-chain-disease protein has been reported.4 Husby, Natvig and Sletten3 described a protein consisting of a single polypeptide chain of approximately 100 amino acids, which was the major constituent of amyloid-fibril proteins from a patient with primary amyloidosis. Aminoacid-sequence analysis showed some homology with the N-terminal aminoacid sequence of X Bence Jones protein and it was suggested that this protein represented a new subtype. Antisera to protein from this patient did not react with any other amyloid preparation or with immunoglobulins or their chains or fragments. The patient's serum contained a protein antigenically related to the amyloid-fibril protein. This serum component was also detected in 5% of sera with M components, whereas a predominance of X light chains was seen among the sera with monoclonal IgG or IgA.6
872 CMA JOURNAL/MAY 22, 1976/VOL. 114
Unlike amyloid fibrils in primary amyloidosis or plasma-cell dyscrasia, the major component of amyloid fibrils in most cases of secondary amyloidosis, as well as in familial Mediterranean fever, is a nonimmunoglobulin protein, AA, * originally described by Benditt and colleagues.7 It consists of 76 amino acids and has a molecular weight of from 7000 to 9000 daltons.8 Husby and associates9 demonstrated this protein in some amyloid fibrils from patients with primary amyloidosis and plasma-cell dyscrasia. Also, the void volume material of secondary amyloid preparations chromatographed on Sephadex G-100 was shown by peptide mapping to be heterogeneous and was believed to be derived from immunoglobulin light chains.'0 It appears, therefore, that amyloid preparations from some patients with primary amyloidosis, myeloma, macroglobulinemia and secondary amyloidosis have common constituents of both immunoglobulin and nonimmunoglobulin origin. This may explain the cross-reactivity observed in gel diffusion between antisera against secondary amyloid and some amyloid preparations from patients with primary amyloidosis and plasma-cell dyscrasia. A serum component, SAA, * antigenically related to the nonimmunoglobulin protein AA, with a-fl electrophoretic mobility and a molecular weight of 100 000, has been demonstrated.1' SAA, which may be a circulating precursor of amyloid fibrils, was detected in serum of patients with all clinical types of amyloidosis as well as in hypogammaglobulinemic serum. SAA was also found in normal adult and cord serum. Its concentration increases with age, pregnancy, tuberculous infection, rheumatoid arthritis, acute infectious disease, biliary cirrhosis, lymphoma, myeloma, macroglobulinemia, carcinoma and all types of amyloidosis.'2 In addition to the fibrillary component, amyloid deposits contain small quantities of a glycoprotein that possesses antigenic identity with a constituent of normal plasma, the P component. It is composed of five globular subunits and has a pentagonal structure. Its molecular weight is approximately 180 000. Initial analysis of the first 23 amino acid residues showed that their sequence differed from all protein sequences known.'3 However, P component of amyloid has since been found to be similar to CiT, a subcomponent *Termmology adopted at International Symposium on Amyloidosis, Helsinki, 1974.
of the first component of complement.'7 Recently the amino acid sequence of amyloid fibrils from medullary carcinoma of the thyroid has been found to be similar to that of calcitonin,'8 and amyloid-like material has been produced in vitro by proteolytic digestion of insulin and glucagon.'9 Despite the impressive advances in our knowledge of the immunochemistry of amyloid, the precise mechanism or mechanisms involved in human amyloidogenesis is not known. In amyloid of immunoglobulin origin and in plasma-cell dyscrasia with amyloid, X light chains predominate, which is the reverse of what is found in plasma-cell dyscrasias not associated with amyloid and in normal immunoglobulins. Also, amyloid fibrils are more readily produced in vitro by peptic digestion of X-type Bence Jones proteins than of K-type proteins;14 this suggests that an amyloidogenic structure is inherent in X light chains. Glenner, Terry and Isersky' have postulated intralysosomal proteolytic digestion of light chains by macrophages as a possible mechanism for amyloid formation. Peptic digestion studies in vitro also have shown that amyloid fibrils originate in similar fragments at an acid pH. Electron microscopy has demonstrated the intracellular localization of amyloid in macrophages." However, in several cases the intact light chain, not its fragments, has been found to be the major component of the amyloid-fibril protein, so that other mechanisms must be considered as well. It has been suggested that light-chain polymers of high molecular weight, which have been reported in serum in several cases associated with amyloidosis, may predispose to the development of amyloid.' It was postulated that such polymers may be precipitated from serum and digested by intracellular lysosomal enzymes of macrophages.' In this regard, we were unable to produce typical amyloid fibrils in vitro by peptic digestion of the purified Bence Jones tetramer of X type from one of the above cases or by digestion of two other purified Bence Jones tetramers of K type. The possibility that light chains and Bence Jones proteins may have antibody activity through the formation of disulfide-linked light-chain dimers has also been proposed.1 The similarity of these dimers to Fab (antigen-binding) fragments provides a theoretical basis for antigen binding.' Serum protein SAA, of high molecular weight, which is believed to be the precursor of the nonimmunoglobulin protein AA and is found in normal serum as well as in all types of amyl-
oidosis, may interact with light chains to form amyloid. In summary, amyloid has a heterogeneous composition, which may be primarily of immunoglobulin or nonimmunoglobulin origin. Normal constituents of plasma antigenically related to amyloid proteins have been identified and are believed to be circulating precursors of amyloid. The relative importance of these plasma factors, as opposed to local factors, and the way in which they interact in amyloid formation remain to be elucidated.
ferent proteins related to ai.Iyloid fibrils. Scand J immunol 3: 391, 1974
7. BEr.rs-r EP, ERIK5EN N, HERMOOSON MA, Ct
8. 9.
10. II.
al: The major proteins of human and monkey amyloid substance: common properties including unusual N-terminal amino-acid sequences. FEBS Lett 19: 169, 1971 SLEl-FEN K, HussY G: The complete aminoacid sequence of non-immunoglobulin amyloid fibril protein AS in juvenile rheumatoid arthritis. Eur I Biochem 41: 117 1974 HUsBY G, SLElTEN K, MIcHAaLss.N TE, et ak Amyloid fibril protein subunit, 'protein AS': distribution in tissue and serum in different clinical types of amyloidosis including that associated with myelomatosis and Waldenstrom's macroglobulinaemia. Scand I Immuno! 2: 395, 1973 LEVIN M, FRANKLIN EC, FRANGIONE B, et al: The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. I Clin Invest 51: 2773, 1972 Hussy G, NATYIG JB: A serum component
related to nonimmunoglobulin amyloid protein AS. a possible precursor of the fibrils.
ALLAN KATZ, MD
Associate professor Department of pathology University of Toronto Toronto, ON
I Clin Invest 53: 1054, 1974 12. ROSENTHAL CI, FRANKLIN EC: Variation with age and disease of an amyloid A proteinrelated serum component. I Clin invest 55:
746, 1975 13. SKINNER M, COHEN AS, SHIRAHAMA T, et al: P-component (pentagonal unit) of amyloid: isolation, characterization, and sequence anal-
W. PRUZANSKI, MD, FRCP[C], FACP
Head, division of immunology Wellesley Hospital Toronto, ON
ysis. I Lab Clin Med 84: 604, 1974 D FRANKLIN EC: Morphologic, chemical, and immunologic studies of amyloid-like fibrils formed from Bence Jones proteins by proteolysis. I Immunol 111: 10, 1973
14. LINKE RP, ZUCKER-FRANKLIN
References 1. GLENNER GG, Tasutv WD, IsERsKY C: Amyloidosis: its nature and pathogenesis. Semin Hematol 10: 65, 1973
15. ZUCKER-FRANKLIN D, FRANKLIN EC: Intracellular localization of human amyloid by fluorescence and electron microscopy. Am /
2. FRANKLIN EC, ZUCKER-FRANKLIN D: Antisera specific for human amyloid reactive with
Pathol 59: 23, 1970 16. DORRINOTON XI, TANFORD C: Molecular size and conformation of immunoglobulins. Adv ImmunoL 12: 233, 1970
conformational antigens. Proc Soc Exp Biol Med 140: 565, 1972
3. GLENNER GG, EIN D, EANES ED, et al: Creation of "amyloid" fibrils from Bence
17. PAINTER RH, PINTERIc L, HOFMANN T, et al:
Jones proteins in vitro. Science 174: 712, 1971
Ultrastructure and chemistry of CIT, subcomponent of Cl: similarity to amyloid Pcomponent. I Immunol (in press) 18. SLETTEN K, WESTERMARK P, NATVIG JD: Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. I Exp Med 143: 993, 1976
4. PRUZANSKI W, KATZ A, NYBERO SC, et at: In vitro production of an amyloid-like substance from gamma 3 heavy chain disease
protein. Immunol Commun 3: 469, 1974 5. HUSBY G, NATVIG JB, SLEITEN K: New third class of amyloid fibril protein. J Exp Med 139: 773, 1974
19. GLENNER GG, EANES ED, BLADEN HA, Ct al: .3-pleated sheet fibrils. A comparison of
6. HUSSY G, NATYIG JB, HARBOE M: The occurrence in sera with M-components of dif-
native amyloid with synthetic protein fibrils. I Histochem Cytochem 22: 1141, 1974
II I. g
ii' I * II I I. I I.' S
S
0
0
*
A
*g.
.
A *
* S
*gg * S
S
9
0 .0. .S . S .
S S
S S
* *
*.
*.
S *.S
S
S A
... 0 S
I
S
* *
S
*, * U gA *gA
*.
A
A
S..
'@.
S
CMA JOURNAL/MAY 22, 1976/VOL. 114 873
