scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
New York ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Subsequent Infection ◽  
Rat Strains ◽  
Wild Rats ◽  
Different Strains ◽  
Rats And Mice

By the inoculation of guinea pigs intraperitoneally with the emulsions of kidneys from wild rats and mice captured in Guayaquil, it was found that 67 per cent of the wild rats tested harbored in their kidneys a leptospira which produced in guinea pigs symptoms and lesions identical with those produced by Leptospira icterohamorrhagia derived either from patients suffering from infectious jaundice in Japan or Europe, or from wild rats caught in New York. Immune sera were prepared in rabbits by injecting different strains of the Guayaquil leptospira. These sera had a marked agglutinating and disintegrating influence upon the homologous strains, and also, but often to a less pronounced degree, upon the strains of Leptospira icterohœmorrhagiœ from other sources. Pfeiffer's phenomenon was also found to be positive, and protection was demonstrated against infection with virulent cultures of strains of Leptospira icterohœmorrhagiœ. The same sera had no effect, or at most a very slight one, upon Leptospira icteroides. Guinea pigs inoculated with icteroides strains were not noticeably protected by the use of the immune sera prepared with the Guayaquil rat strains. Guinea pigs inoculated with killed cultures of the Guayaquil strains of leptospira proved to be resistant to a subsequent infection with heterologous as well as homologous strains of Leptospira icterohœmorrhagiœ. It is concluded, therefore, that the leptospira isolated from the kidneys of wild rats and mice in Guayaquil belongs to the group of Leptospira icterohœmorrhagiœ, and differs from Leptospira icteroides in its immunity reactions. No positive transmission was obtained with kidney material from bats and an opossum.

scholarly journals A COMPARATIVE STUDY OF EXPERIMENTAL PROPHYLACTIC INOCULATION AGAINST LEPTOSPIRA ICTEROHÆMORRHAGIÆ

1918 ◽  
Vol 28 (5) ◽  
pp. 561-570 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Guinea Pigs ◽  
Lethal Dose ◽  
General Rule ◽  
Subsequent Infection ◽  
Japanese Strain ◽  
Active Immunity ◽  
American Strain ◽  
Pure Cultures ◽  
Different Strains

Guinea pigs were inoculated with suspensions of Leptospira icterohæmorrhagiæ obtained from pure cultures of several different strains, in order to determine whether or not an active immunity against a subsequent infection with virulent organisms would develop in the vaccinated animals. The experiments were so arranged as to make possible a determination of the existence of immunity against homologous strains as well as against the strains not employed as vaccine, and a brief quantitive estimation of the degree and duration of the immunity in relation to the quantities of the vaccines inoculated. Following the general rule of prophylactic inoculations with various pathogenic organisms, the inoculations were repeated subcutaneously on three consecutive occasions at intervals of 5 days. With respect to the amounts of vaccine, the experiments were divided into three groups for each vaccine, one group receiving three doses of 0.5 cc., the second three of 0.05 cc., and the third three of 0.005 cc. Four different strains were employed as vaccines, American Strain 1, American Strain 2, and one each of the Japanese and the European strains. The determination of the development, degree, and duration of the immunity was made by inoculating intraperitoneally several minimum lethal doses of each of the five following strains: American Strains 1, 2, and 3, the Japanese, and the European strains. The virulence of the different strains varied considerably, the strongest being the Japanese strain, which killed the guinea pig in a dose of 0.00001 cc., and the weakest American Strain 3, the minimum lethal dose of which was as large as 0.01 cc. The vaccinated guinea pigs were tested for immunity at the end of 2, 4, and 8 weeks after the last inoculation. The results obtained show that three successive inoculations of 0.5 cc. of the emulsions of killed cultures of Leptospira icterohæmorrhagiæ into guinea pigs rendered them completely resistant to a subsequent infection with the virulent cultures of both homologous and heterologous strains. With 0.05 cc. the protection was not so general, the animals succumbing to an experimental infection with some heterologous strains while resisting the homologous and other heterologous strains. The animals which were vaccinated with 0.005 cc. survived the infection experiments with the homologous strains in the case of American Strain 1 and the Japanese strain, but they were not protected against any other strains. The vaccines of other strains were unable to immunize the guinea pigs so highly even against their homologous strains, when the amount of each inoculation was only 0.005 cc., but 0.05 cc. conferred complete protection against the same strains. It may be concluded, therefore, that when a sufficient quantity of killed cultures of Leptospira icterohæmorrhagiæ is given, the guinea pigs will become immune to all strains of the same organism, but that smaller quantities may protect them against homologous but not against heterologous strains. A close analysis reveals the existence of group or type affinities among different strains which can be brought ' out by immunizing the animals with smaller quantities of killed cultures. In the present series of experiments American Strains 1 and 3 form one group, American Strain 2 and the European strain another, and the Japanese strain a third, which is also closely allied to the first group. In order to insure universal immunity it is wise to employ as many group or type cultures as possible in the preparation of vaccines, a polyvalent vaccine being recommended. It is not improbable that the strain recently encountered in Lorient, France, is an unusually deviated type of Leptospira icterohæmorrhagiæ, and that if successfully cultivated and used as vaccine in sufficient amount it might protect the animals against other strains of the same organism. The active immunity induced in the vaccinated guinea pigs was found to persist for at least 8 weeks after the last inoculation. It will no doubt last for a much longer period.

scholarly journals IMMUNOLOGY OF THE PERUVIAN STRAINS OF LEPTOSPIRA ICTEROIDES

1921 ◽  
Vol 33 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler
Keyword(s):  
New York ◽  
Guinea Pig ◽  
Incubation Period ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Rabbit Serum ◽  
Minimum Lethal Dose ◽  
Lethal Doses

Serum from yellow fever convalescents from Payta, Piura, and Morropon gave a positive Pfeiffer reaction with the strains of Leptospira icteroides isolated in Guayaquil and Merida. The serum also protected the guinea pigs from these strains in the majority of instances. The Pfeiffer reaction was complete with all recent convalescents (7 to 36 days) but slight or partial in some instances with serum derived from individuals who had had the attack of yellow fever 10 months previously. The virulence of the Morropon strains was found to be approximately the same as that of the Guayaquil or Merida strains. With one strain the minimum lethal dose for the guinea pig was less than 0.00001 cc. of a kidney emulsion from an infected guinea pig. Suitable quantities of the anti-icteroides serum administered to guinea pigs inoculated with 2,000 to 20,000 minimum lethal doses of infective material prevented the development of the infection, or a fatal outcome, according as the serum was given during the incubation period or after fever had appeared. The earlier the administration of the serum the smaller was the quantity needed; during the incubation period 0.0001 to 0.001 cc. was sufficient, during the febrile period 0.01 to 0.1 cc. was required to check the progress of the disease, and even at the time when jaundice had already appeared, the injection of 0.1 to 1 cc. saved three out of four animals inoculated with Strain 3 and one out of three inoculated with Strain 1. The native guinea pigs secured in Payta proved to be unusually refractory to infection with Leptospira icteroides as compared with normal guinea pigs recently imported from New York. Fresh rabbit serum is recommended for culture work with Leptospira icteroides.

scholarly journals EXPERIMENTAL STUDIES ON YELLOW FEVER IN NORTHERN PERU

1921 ◽  
Vol 33 (2) ◽  
pp. 239-252 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler
Keyword(s):  
New York ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Culture Media ◽  
Experimental Studies ◽  
Dark Field ◽  
Practical Significance ◽  
Rabbit Serum ◽  
Laboratory Facilities ◽  
Northern Peru

Fourteen typical cases of yellow fever were studied in northern Peru during an epidemic occurring in 1920, nine in Payta in March and April, and five in Morropon and Piura in April and May. The method of investigation was similar to that previously employed, but as the laboratory facilities were very meager certain changes were required. Although in Payta the work was handicapped by the lack of electric light, the scarcity of water and animal food, the unsuitability of the guinea pigs for inoculation, and the changes in culture media due to age, the results obtained under these adverse conditions were by no means negative. While in no instance was there a typical infection produced in animals, either by direct inoculation of blood or with culture materials, yet certain guinea pigs in each series showed temporary febrile reactions or definite hemorrhagic lesions of the lungs indicative of a mild leptospira infection. Direct search for Leptospira icteroides in the blood of patients or in culture materials was not made because the dark-field microscope could not be used. Subsequently, at Piura, the laboratory facilities were vastly, improved, the use of the dark-field microscope was made possible by means of a storage battery, and a fresh stock of young healthy guinea pigs was received from New York, and fresh rabbit serum obtained in Piura. In the study of the materials obtained from five cases of yellow fever in Morropon all these added facilities were taken advantage of, with the result that the outcome was positive and convincing. Cultures from the five cases were examined after 11, 12, and 13 days, and in those from three cases living leptospiras were found. By inoculation into suitable guinea pigs of culture material from these five cases, irrespective of whether or not leptospiras were detected under the dark-field microscope, a typical Leptospira icteroides infection was produced from four of the five cases. In one of these no leptospira had been detected in the culture tubes. Thus one case only yielded negative results, in that no leptospiras were found under the dark-field microscope and the animal inoculation was negative. The leptospira was demonstrated in the blood or organ emulsions of the infected guinea pigs, and further transmission of each strain to other guinea pigs was obtained and pure cultures were secured. A few points of practical significance appeared in the course of the present investigation. One is the importance of using fresh rabbit serum for culture media. Old rabbit serum, whether in pure form or incorporated with agar, etc., which had been kept for several months in a tropical climate, proved to be unsatisfactory for obtaining a growth of Leptospira icteroides. A second point of interest is the variation in susceptibility of guinea pigs to infection with Leptospira icteroides. In two of four series of positive animal inoculations with the Morropon culture materials only one-half of the guinea pigs inoculated with given materials developed typical symptoms. The other half either suffered from a transient mild infection, as evidenced by a few hemorrhagic foci in the lungs, or escaped infection altogether. From these facts it is highly probable that the lung lesions and febrile reactions observed in certain guinea pigs inoculated with the Payta materials were due to a mild leptospira infection. In a comparative experiment the native guinea pigs procured in Payta were found to be more resistant to the leptospira infection than those recently brought from New York. In fact, only a small portion of the former succumbed to typical infection even when inoculated with a virulent strain of Leptospira icteroides obtained from the Morropon epidemic. In conclusion it may be stated that of fourteen cases of yellow fever studied in Peru, a typical leptospira infection, together with the demonstration of the organism in experimentally infected guinea pigs, was obtained in four, while in the majority of instances indications of a mild, non-fatal leptospira infection were observed. In a few cases only were the results entirely negative. The leptospira isolated from Morropon cases of yellow fever, which is morphologically and culturally identical with the Guayaquil and Merida strains of Leptospira icteroides, was also shown by immunity test to be indistinguishable from the Guayaquil organism.

Histamine catabolism in guinea pigs, rats and mice

1974 ◽  
Vol 25 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Richard W. Schayer ◽  
Margaret A. Reilly
Keyword(s):  
Guinea Pigs ◽  
Rats And Mice

scholarly journals EXPERIMENTAL STUDIES ON YELLOW FEVER OCCURRING IN MERIDA, YUCATAN

1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler
Keyword(s):  
Guinea Pig ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Secondary Infection ◽  
Fatal Case ◽  
Primary Cultures ◽  
Experimental Studies ◽  
Dark Field ◽  
Liver And Kidney ◽  
Positive Direct

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure

THE IN VITRO METABOLISM OF MAMMARY GLAND SLICES IN THE PRESENCE OF POSTERIOR PITUITARY LOBE EXTRACTS RICH IN MELANOPHORE-DISPERSING ACTIVITY

1957 ◽  
Vol 15 (4) ◽  
pp. 366-373 ◽  
Author(s):  
T. R. BRADLEY ◽  
G. M. MITCHELL
Keyword(s):  
Mammary Gland ◽  
Guinea Pigs ◽  
Incubation Medium ◽  
Mammary Glands ◽  
Gas Evolution ◽  
Early Lactation ◽  
Posterior Pituitary ◽  
Rats And Mice ◽  
Posterior Pituitary Lobe

SUMMARY Slices cut from mammary glands of rats and mice during gestation and lactation were incubated in vitro in the presence of pig posterior pituitary lobe extracts rich in melanophore-dispersing ('B') activity. Slices taken in early lactation but not during gestation or late lactation showed increased net gas evolution compared with control slices. Similar tissue from rabbits and guinea-pigs did not give rise to this effect, nor did slices of other tissues taken from lactating rats. The increased net gas evolution was not observed in the absence of glucose from the incubation medium. Treatment of the 'B' extract with NaOH or hypophysectomy of the rats prior to use decreased the response.

scholarly journals SPIROCHÆTA MORSUS MURIS, N.SP., THE CAUSE OF RAT-BITE FEVER

1917 ◽  
Vol 25 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Kenzo Futaki ◽  
Itsuma Takaki ◽  
Tenji Taniguchi ◽  
Shimpachi Osumi
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Clinical Symptoms ◽  
Intermittent Fever ◽  
Lymph Glands ◽  
Short Forms ◽  
White Rats ◽  
Rat Bite Fever ◽  
Rats And Mice ◽  
Aniline Dyes

1. Since our first report on the discovery of the cause of rat-bite fever, we have been able to prove the existence of the same spirochete in five out of six more cases which have come under our observation. 2. The clinical symptoms of rat-bite fever are inflammation of the bitten parts, paroxysms of fever of the relapsing type, swelling of the lymph glands, and eruption of the skin, all occurring after an incubation period usually of from 10 to 22 days, or longer. 3. Our spirochete is present in the swollen local lesion of the skin and the enlarged lymph glands. But as the spirochetes are so few in number it is exceedingly difficult to discover them directly in material taken from patients. It is therefore better to inoculate the material into a mouse. In some cases the organism is found in the blood of the inoculated animal after a lapse of 5 to 14 days, or at the latest 4 weeks. 4. Generally speaking, the spirochetes present thick and short forms of about 2 to 5 µ and have flagella at both ends. Including the flagella, they measure 6 to 10 µ in length. Some forms in the cultures reach 12 to 19 µ excluding the flagella. The curves are regular, and the majority have one curve in 1 µ. Smaller ones are found in the blood and larger ones in the tissues. 5. The spirochetes stain easily. With Giemsa's stain they take a deep violet-red; they also stain with ordinary aniline dyes. The flagella, too, take Giemsa's stain. 6. The movements of our spirochetes are very rapid, resembling those of a vibrio, and distinguish them from all other kinds of spirochetes. When, however, the movements become a little sluggish, they begin to present movements characteristic of ordinary spirochetes. 7. For experimental purposes, mice, house rats, white rats, and monkeys are the most suitable animals. Monkeys have intermittent fever after infection, and spirochetes can be found in their blood, but they are not so numerous as in the blood of mice. Mice are the most suitable animals for these experiments, and they appear, as a rule, to escape fatal consequences. 8. The spirochete is markedly affected by salvarsan. 9. The organism is not present in the blood of all rats, and there is no relation between the species of the rat and the ratio of infection. We have never found the spirochete in healthy guinea pigs or mice. By permitting a rat infected with the spirochete to bite a guinea pig, the latter develops the disease. 10. We have succeeded in cultivating the spirochete in Shimamine's medium. 11. Among the spirochetes described in the literature or discovered in the blood of rats and mice, there may be some resembling our spirochete, but none of the descriptions agree with it fully. Hence we have named our organism Spirochæta morsus muris and regard it as belonging to the Spironemacea (Gross) of the nature of treponema. 12. The spirochete can be detected in the bodies of patients. In seven cases out of eight, it disappears on recovery, only to reappear during the relapse. 13. The spirochete can be detected in about 3 per cent of house rats. These facts enable us to identify the cause of the disease. 14. There may be other causes than the spirochete for diseases following the bite of a rat. The cause, however, of rat-bite fever in the form most common in Japan is, we believe, the spirochete which we have described.

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