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Cardiotoxicity of streptolysin “O” in mammals: A pathophysiological study
Abstracts
141
CHEMICAL STUDIES ON A PHARMACOLOGICALLY ACTIVE POLYPEPTIDE FRAGMENT ISOLATED FROM TETANUS TOXIN BERNARD BIZZZNI
Head of Laboratory, Pasteur Institute, Paris, France An atoxic, but antigenic tetanus toxin fragment was isolated and purified either from the frozen crude or papain-digested pure tetanus toxin. The fragment was characterized physicochemically and chemically. From an immunological viewpoint, the fragment was shown to cross-react with the heavy but not with the light chain of which the toxin molecule is built up. Moderate papain digestion of the heavy chain yielded a degradation product which is immunologically identical with the atoxic tetanus toxin fragment . The toxin fragment and the heavy chain were capable of binding to insolubilized gangliosides. Thus, it is postulated that the binding site of the toxin to its receptors is likely to be located on the heavy chain. Consequently, the binding site and the toxophore group might represent separate parts of the toxin molecule.
DETECTION IN THE U .S.S.R . OF CL. BOTULINUM TYPE F AND TTS DIFFERENTIAL DIAGNOSIS WITH TYPE E T. I. Buc,w~rovw, I. F. Cxur xovw, L. I. Ar~ovw and I. S. KwzDDHtNw Institute of Epidemiology and Microbiology, Academy of Medical Sciences, U.S.S.R . Theauthors present material obtained in studying 1949 samples of soil, sea ground and faces of dears for
Cl . botulinum . The causative agents of botulism were revealed in 131 samples, of this number of type A-in
6, of type B-in 20, of type C-in 2, of types A + C - in 10 of type E-in 26 and of type F-in 67. The method of differential diagnosis between types E and F by neutralization reaction on albino mice is presented . The antisera were diluted to the concentration of 1 i.u ./ml for differentiation of the toxins types E and F in the neutralization test . A total of 1859 samples of fish and animals were examined for contamination with the causative agent of botulism . The culture fluid of 4-5 day cultures of the samples was tested by neutralization reaction with the diagnostic antitoxic antibotulinium sera, types A, B, C, E. Thecausative agents of botulism [types A-7, B-16, C-5, E-128] were revealed in 156 samples. The entrees types E and F were diluted to the concentration of 1 i.u ./ml for differentiation of the toxins (types E and F) in the neutralization test. Of 128 samples which gave a positive reaction with the serum of type E, 75 were identified as type F. The authors recommend in all cases of botulism of type E in man to carry out differential diagnosis between the causative agents of botulism of types E and F and, on the basis of these data, to solve the problem of the necessity of production of therapeutic antibotulinum serum of type F. The isolated pure Cl, botulirurm strains type F had biological activity ranging from 100 to 500,000 MLD/ml for albino mice .
CARDIOTOXICITY OF STREPTOLYSIN "O" IN MAMMALS: A PATHOPHYSIOLOGICAL STUDY R. K. Gurrw and Sus~w Gurrw M.L .B . Medical College, Jhansi (UP), India Rheumatic pancardititios is one of the most frequent post-streptocoocal sequel ; these patients, more so during the phase of acute rheumatic activity, frequently show disruption of cardiac activity. Though the exact pathogenetic mechanisms) involved in the causation of rheumatic carditis are not well known, hypersensitivity to streptococcal cell wall antigens) has been widely incriminated in the causation of this disease. Although, this hypothesis partly explains the development of some of the histomorphological lesions seen in the heart, it is, however, not adequate to explain the complete picture of rheumatic pancarditis and associated myocardial failure in man. Whether steptolysin 'O' (a streptococcal exotoxin) could play any significant role in the causation of cardiac lesions and disruption of cardiac activity in these patients has been the subject for investigation . With this objective we have investigated the cardiotoxic effects of streptolysin `O' in experimental animals. The intraperitoneal administration of streptolysin `O' (4U/rat) produced only focal cardiac lesions; intrapericardial administration of streptolysin `O' (2U/rat), besides the involvement of the myocardium, also caused the development of exudative lesions in the pericardium and valvular endocardium (pancarditis) . Small doses of streptolysin `O' also caused marked depression or complete cessation of myocardial contractility of isolated atria of rabbit and guinea pig and the atria and ventricles of rat and dog and ventricles of cat In vivo. The electrocardiographic investigations also revealed that both in tho rabbits as well as the dogs, the intravenous administration of small doses of streptolysin 'O' caused marked disruption of cardiac aMivity. These observations would therefore suggest that streptolysin `O' is a potent cardiotoxin and may be involved in the causation of acute rheumatic pancarditis and associated myocardial failure during acute, rheumatic fever in man.
141
CHEMICAL STUDIES ON A PHARMACOLOGICALLY ACTIVE POLYPEPTIDE FRAGMENT ISOLATED FROM TETANUS TOXIN BERNARD BIZZZNI
Head of Laboratory, Pasteur Institute, Paris, France An atoxic, but antigenic tetanus toxin fragment was isolated and purified either from the frozen crude or papain-digested pure tetanus toxin. The fragment was characterized physicochemically and chemically. From an immunological viewpoint, the fragment was shown to cross-react with the heavy but not with the light chain of which the toxin molecule is built up. Moderate papain digestion of the heavy chain yielded a degradation product which is immunologically identical with the atoxic tetanus toxin fragment . The toxin fragment and the heavy chain were capable of binding to insolubilized gangliosides. Thus, it is postulated that the binding site of the toxin to its receptors is likely to be located on the heavy chain. Consequently, the binding site and the toxophore group might represent separate parts of the toxin molecule.
DETECTION IN THE U .S.S.R . OF CL. BOTULINUM TYPE F AND TTS DIFFERENTIAL DIAGNOSIS WITH TYPE E T. I. Buc,w~rovw, I. F. Cxur xovw, L. I. Ar~ovw and I. S. KwzDDHtNw Institute of Epidemiology and Microbiology, Academy of Medical Sciences, U.S.S.R . Theauthors present material obtained in studying 1949 samples of soil, sea ground and faces of dears for
Cl . botulinum . The causative agents of botulism were revealed in 131 samples, of this number of type A-in
6, of type B-in 20, of type C-in 2, of types A + C - in 10 of type E-in 26 and of type F-in 67. The method of differential diagnosis between types E and F by neutralization reaction on albino mice is presented . The antisera were diluted to the concentration of 1 i.u ./ml for differentiation of the toxins types E and F in the neutralization test . A total of 1859 samples of fish and animals were examined for contamination with the causative agent of botulism . The culture fluid of 4-5 day cultures of the samples was tested by neutralization reaction with the diagnostic antitoxic antibotulinium sera, types A, B, C, E. Thecausative agents of botulism [types A-7, B-16, C-5, E-128] were revealed in 156 samples. The entrees types E and F were diluted to the concentration of 1 i.u ./ml for differentiation of the toxins (types E and F) in the neutralization test. Of 128 samples which gave a positive reaction with the serum of type E, 75 were identified as type F. The authors recommend in all cases of botulism of type E in man to carry out differential diagnosis between the causative agents of botulism of types E and F and, on the basis of these data, to solve the problem of the necessity of production of therapeutic antibotulinum serum of type F. The isolated pure Cl, botulirurm strains type F had biological activity ranging from 100 to 500,000 MLD/ml for albino mice .
CARDIOTOXICITY OF STREPTOLYSIN "O" IN MAMMALS: A PATHOPHYSIOLOGICAL STUDY R. K. Gurrw and Sus~w Gurrw M.L .B . Medical College, Jhansi (UP), India Rheumatic pancardititios is one of the most frequent post-streptocoocal sequel ; these patients, more so during the phase of acute rheumatic activity, frequently show disruption of cardiac activity. Though the exact pathogenetic mechanisms) involved in the causation of rheumatic carditis are not well known, hypersensitivity to streptococcal cell wall antigens) has been widely incriminated in the causation of this disease. Although, this hypothesis partly explains the development of some of the histomorphological lesions seen in the heart, it is, however, not adequate to explain the complete picture of rheumatic pancarditis and associated myocardial failure in man. Whether steptolysin 'O' (a streptococcal exotoxin) could play any significant role in the causation of cardiac lesions and disruption of cardiac activity in these patients has been the subject for investigation . With this objective we have investigated the cardiotoxic effects of streptolysin `O' in experimental animals. The intraperitoneal administration of streptolysin `O' (4U/rat) produced only focal cardiac lesions; intrapericardial administration of streptolysin `O' (2U/rat), besides the involvement of the myocardium, also caused the development of exudative lesions in the pericardium and valvular endocardium (pancarditis) . Small doses of streptolysin `O' also caused marked depression or complete cessation of myocardial contractility of isolated atria of rabbit and guinea pig and the atria and ventricles of rat and dog and ventricles of cat In vivo. The electrocardiographic investigations also revealed that both in tho rabbits as well as the dogs, the intravenous administration of small doses of streptolysin 'O' caused marked disruption of cardiac aMivity. These observations would therefore suggest that streptolysin `O' is a potent cardiotoxin and may be involved in the causation of acute rheumatic pancarditis and associated myocardial failure during acute, rheumatic fever in man.