A new mycobacterial infection in man.

Es sind jetzt 10 Jahre verflossen, seitdem ich mit Volhard zusammen Uber das Ergebnis unserer 4 Jahre lang auf dem Gebiet des Morbus Brightii gemeinsam betriebenen Studien berichtete. Schon damals beim Erscheinen dieser Arbeit hatten sich Kliniker und Anatomen wieder mit erneutem Eifer den hierin Frage kommenden Problemen zugewandt (siehe die Arbeiten der Aschoffschen Schule, von Jores, Lohlein, Munk, Schlayer u. a.); durch den Krieg, durch das gehaufte Auftreten der „Kriegsnephritis“ sind diese Fragen noch mehr in den Mittelpunkt des Interesses geruckt und seitdem in standigem Flus geblieben. Die Zusammenarbeit zwischen Volhard und mir ist bald nach dem Erscheinen unserer Monographie durch ausere Umstande unterbrochen worden und jeder von uns ist dann seine eigenen Wege weitergewandert. Volhard hat vor einigen Jahren von neuem im Handbuch von Mohr und Staehelin seine khnischen Erfahrungen niedergelegt und auch ich mache in dem vorliegenden Buch zum zweiten Male den Versuch, meine in den vergangenen Jahren unablassig weiter betriebenen Studien auf dem Gebiete der Nierenpathologie zusammenfassend darzustellen, nachdem ich schon bezuglich einer Reihe von Einzelfragen, uber die eine Ubereinstimmung der Meinungen bis jetzt noch nicht erzielt werden konnte, besonders auf dem Gebiet der Nephrose, der herdformigen Glomerulonephritis und der Nephrosklerose in kurzeren Abhandlungen meine ursprungliche Meinung weiterentwickelt, ausgebaut, vielfach auch modifiziert habe.

Pathologische Anatomie des Morbus Brightii

Einleitung. Auf Grund unserer vorhergehenden experimentellen Untersuchungen 1 sind wir zur Uberzeugung gelangt, dal] fiir die Pathogenese der diffusen Glomerulonephritis die Allergic eine mal~gebende Rolle spielt. Die histologischen Eigent~mlichkeiten dieser Nierenerkrankung, die man bisher mit Zuhilfenahme der Entzfindungsoder Gefal~krampflehre nieht restlos aufldaren konnte, kSnnen dutch die 2umahme, dal~ es sich hier um eine hypercrgische/~ea~ion der Niere gegen irgendein Eiweil~antigeff handelt, zum besseren Verst~ndnis gebracht werden. Soweit Infektionen in lVrage kommen, scheint mehr die {}berempfindlichkeit gegen Bakterien oder Toxine als die direkte Wirkung dieser in Frage kommen. ~_hnliehe Gedanken wurden seit Schiclc und v. Pirquet yon manehen Klinikern ge/~ul~ert, haben abet yon seiten der Pathologen keine Anerkennung erfahren. Da wit aber bisher unsere diesbeziigliohe Ansicht aussehlie6lich auf die experimentelle Glomerulonephritis begrtindeten, die durch Injektion des spezifischen Antinierenserums bei Tieren erzeugt wird, so erschien uns notwendig, jetzt bei sensibilisierten Tieren die geweblichen Ver/~nderungen der lqiere auf das Allergen zu untersuchen. Wie bekalmt, ]iegt bis jetzt eine kaum iibersehbare Ftille yon Arbeiten vor, die sieh mit der experimentellen Erzeugung der Glomerulonephritis befassen. Von der Annahme ausgehend, dal3 die im Blur kreisenden Bakterien oder deren Toxine direkt das Nierengewebe schgdigen, versuchte man zungehst dutch Einspritzung yon Bakterien oder Toxinen bei Tieren eine Nierenerkrankung im Sinne der diffusen Glomerulonephritis zu erzeugen. Der Erfolg blieb aus. Man gewann einheitliehe umschriebene Lgsionen der Glomeruli wie Nekrosis, lakunenartige Capillarektasie oder entztindliehe Vorggnge, die kaum in der Richtung der menschlichen diffusen Glomerulonephritis liegen (Literaturiibersicht bei Patrassi 1932). Da die Annahme nahe lag, dal~ fiir die Pathogcnese dieser 2qierenerkrankung die immunisatorisehen Vorggnge eine Rollc

Über die allergische Gewebsreaktion der Niere

Vaccinology, the concept of a science ranging from the study of immunology to the development and distribution of vaccines, was a word invented by Jonas Salk. This book covers the history of the methodological progress in vaccine development and to the social and ethical issues raised by vaccination. Chapters include "Jenner and the Vaccination against Smallpox," "Viral Vaccines," and "Ethical and Social Aspects of vaccines." Contributing authors include pioneers in the field, such as Samuel L. Katz and Hilary Koprowski. This history of vaccines is relatively short and many of its protagonists are still alive. This book was written by some of the chief actors in the drama whose subject matter is the conquest of epidemic disease.

History of vaccine development

Mycobacterium (Gr. n. myces a fungus; Gr. neut. dim. n. bakterion a small rod; M.L. neut. n. Mycobacterium a fungus rodlet) is undeniably one of the most clinically important and intensively studied of bacterial taxa. Tuberculosis and leprosy, the most significant diseases caused by mycobacteria, have been recognized throughout recorded times. The taxonomic history of the genus Mycobacterium is intricate and difficult to disentangle from that of related taxa, notably Corynebacterium, Nocardia, and Rhodococcus (1). Comprehensive reviews on the early taxonomic history of these genera are available (2, 3, 4, 5, 6, 7).

Taxonomy of Mycobacteria

1. Broth-grown cultures, cultures from blood agar slants and culture filtrates (Berkefeld N or V) of H. Streptococcus scarlatinae are without appreciable effect upon the rabbit, no matter how large the dose or by what route introduced. 2. The active toxic principle of H. Streptococcus scarlatinae for rabbits is intimately associated with the protein of the bacterial cell, and is not given off in the artificial medium during the growth activity of the organism, indicating, therefore, its endotoxic character. 3. The endotoxin is readily obtained from the viable scarlatinal cultures through the medium of the peritoneal cavity of the rabbit immunized against the homologous strain (Pfeiffer phenomenon). The toxic substance thus obtained we have termed a lysate. 4. The rabbit is highly susceptible to the in vivo prepared lysate of Streptococcus scarlatinae, at least from the cultures we have employed. The degree of the toxic effect upon the rabbit depends upon the size of the dose and the route through which it is introduced. The specific effects range from mild to severe and fatal forms of toxemia as indicated by high fever, leucocytosis, paralysis and acute hemorrhagic glomerular nephritis. 5. The experimentally induced nephritic lesions are analogous in kind and variety to those of acute scarlatinal nephritis in man, including the "epithelial crescent" formation, hyaline thrombi of glomerular capillaries, hemorrhage into capsular space and necrosis of capillary tufts.

https://rupress.org/jem/article-pdf/44/4/567/1177608/567.pdf

Experimental glomerulonephritis induced in rabbits with the endotoxic principle of streptococcus scarlatinæ

The cutaneous reaction demonstrates that the culture lysate of Streptococcus scarlatinae is approximately ten time more potent in its toxic effect than is the culture filtrate since repeated and carefully controlled human skin tests show that 0.1 cc. of a 1:2000 dilution of lysate reacts equally as well as a similar dose of a 1:250 dilution of culture filtrate (Dick's standard skin unit).

Animal tests and the human intradermal reaction clearly reveal that the toxic principle of culture filtrate (Dick's toxin) and culture lysate (Duval-Hibbard endotoxin) are of the same nature) namely intracellular derivatives of the streptococcal cell.

The in vivo prepared lysate affords a more potent antigen for the production of an antiendotoxic serum than the living, killed or culture filtrate of Streptococcus scarlatinae .

The inoculations into dogs of culture filtrate and of the "washed coccal bodies" yield strikingly different results. In those that receive filtrate no toxic effect is produced while in the ones injected with the washed coccal bodies a severe and often fatal toxemia results.

The dog is highly susceptible to infection with Streptococcus scarlatinae and also readily affected by injections of the in vivo prepared lysate. Toxic effects are produced almost immediately following the intravenous injection of lysate and death usually occurs in 24 to 48 hours from an acute hemorrhagic nephritis. Daily urinary examination shows a high percentage of albumin, large numbers of fine granular casts and quantities of macroscopic blood. A study of the kidney sections reveals an extensive glomerulonephritis.

The work reported constitutes further evidence in support of our original contention that the poisonous substance of the scarlatinal streptococcus is derived from the bacterial cell set free through the dissolution of the germ plasm. The liberation of the poison in vitro occurs as the natural result of autolysis while in vivo it is produced through specific action of bacteriolysin.

https://rupress.org/jem/article-pdf/46/2/379/1177892/379.pdf

Nature of the toxic moiety of streptococcus scarlatinae.

Pure cultures of an acid-fast bacillus were cultivated upon special media from the human tissues in four cases of leprosy. The nature of the growth, morphological characters and tinctorial properties do not differ for any of the cultures and correspond closely to the bacilli in the human leprous tubercles. That the bacillus of leprosy will multiply and continue to do so indefinitely outside of the animal body was first demonstrated by Clegg who cultivated an acid-fast organism from leprosy tissue in the presence of ameba and their symbiotics. Not only have I been able to confirm Clegg's work, but in addition I have succeeded in growing the bacillus in pure culture and in reproducing the disease in the Japanese dancing mouse, thereby establishing its identity. This species of animal acquires the infection in four to six weeks after intraperitoneal or subcutaneous inoculation with either emulsions of fresh leprous tissue or the pure cultures of B. leprae. Comparatively few bacilli are necessary to infect the mouse; and the mode of inoculation does not seem to make any appreciable difference in respect to the nature and time of development of the lesion. The experimental lesions are proliferative in character and identical with those in the human subject. Macroscopically they appear as glistening, white nodules which, in the early stages of development, resemble miliary tubercles. In my experience neither the cultures nor the bacilli directly from the human tissues have shown any evidence of multiplication or given rise to lesions when injected into the ordinary laboratory animals such as guinea pigs, rabbits, gray and white mice and rats, although repeated attempts have been made to infect these animals. B. leprae will not only multiply but it will colonize on a plain agar medium seeded with a pure culture of encysted ameba (Plate LVIII, Fig. 5), and upon an agar or banana medium prepared with a I per cent. solution of cystein and tryptophane. Colonization occurs in the form of glistening, white colonies, one to two millimeters in diameter, in from one to two months incubation. The bacilli in cultures are at all times acid-fast and differ only in morphology from those of the tissues in that they exhibit a greater variation in the distribution of the chromatin and are longer and more distinctly curved. To prove that the cultures obtained from the human tissues of these four cases are leprosy bacilli and not some other acid-fast species, the following facts are offered: (1) the growth features are distinctive and multiplication takes place only under special conditions of temperature and medium; (2) the complete correspondence in tinctorial properties and similarity in morphology to those in the tissues; (3) the failure to multiply or produce lesions in the common laboratory animals; and (4) the growth of the bacilli and the production of typical leprous lesions in the Japanese dancing mouse. The successful cultivation of B. leprae and the fact that the cultures retain pathogenic properties are of commanding importance in respect to a possible production of an artificial immune serum for combating the infection in man. Work along this interesting line is already in progress in our laboratories.

https://rupress.org/jem/article-pdf/12/5/649/1392510/649.pdf

The cultivation of the leprosy bacillus and the experimental production of leprosy in the japanese dancing mouse.

The present communication is to report briefly the results obtained in our efforts to induce nephritis in the rabbit with the active principle of the scarlatinal streptococcus In a previous paper we 1 reported our experiments, which seemed to prove that the toxic moiety ofStreptococcus scarlatinae, at least for the rabbit, is intimately bound up in the protoplasm of the bacterial cell, and is therefore endotoxic in character With this toxic substance we have succeeded in producing in the rabbit the acute glomerular lesions that occur in the kidneys of human scarlet fever In this connection we can say with assurance that the acute stage of renal change in this animal is caused by a protein intoxication, and not by the presence in the tissues of the streptococcus itself The streptococcal toxic substance employed by us in the production of acute glomerulonephritis was secured either through the medium of

Experimental production of acute glomerulonephritis: use of active principle of scarlatinal streptococcus and a consideration of chronic interstitial changes: preliminary report

From the observations herein reported for our series of vaccinations we believe there is every indication that the influenza protein employed gives rise to the production of protective substances and therefore justifies its use in the prophylaxis of epidemic influenza

Charles W. Duval

Papers

Experimental glomerulonephritis induced in rabbits with the endotoxic principle of streptococcus scarlatinæ

Nature of the toxic moiety of streptococcus scarlatinae.

The cultivation of the leprosy bacillus and the experimental production of leprosy in the japanese dancing mouse.

Experimental production of acute glomerulonephritis: use of active principle of scarlatinal streptococcus and a consideration of chronic interstitial changes: preliminary report

The Antigenic Property of the Pfeiffer Bacillus As Related to Its Value in the Prophylaxis of Epidemic Influenza