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

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Dark Field ◽  
Blood Film ◽  
Fresh Blood ◽  
The Third ◽  
Fresh State ◽  
Liver And Kidney ◽  
Made In

Examinations of fresh blood from yellow fever patients by means of the dark-field microscope, made in more than twenty-seven cases, revealed in three cases the presence of Leptospira icteroides. In no instance was a large number of organisms found, a long search being required before one was encountered. The injection of the blood into guinea pigs from two of the three positive cases induced in the animals a fatal infection, while the blood from the third positive case failed to infect the guinea pigs fatally. Careful but by no means exhaustive dark-field searches for the leptospira with fresh specimens of blood from the remaining cases of yellow fever ended without positive findings, although four of the specimens, when injected into guinea pigs, caused a fatal leptospira infection. Stained blood film preparations from the corresponding cases were also examined, but the percentage showing the leptospira in the blood was no greater than that found by examination in the fresh state with the dark-field microscope. In fact, owing to the defective stains that were available at the time of the investigation a great many slides did not take the proper coloration with Giemsa's or Wright's stain and could not be relied upon. Regarding the presence of Leptospira icteroides in various organs both dark-field and stained films were examined. In only one instance so far a few organisms were detected in the emulsion of liver taken shortly after death from a case dying on the 4th day of yellow fever. This part of the work will be reported later upon completion. Examinations of the urine from different cases of yellow fever were made both by dark-field microscope and by inoculation into guinea pigs. The results were totally negative in thirteen cases, including many convalescents, but in one case one of the guinea pigs inoculated with 10 cc. of the urine came down on the 15th day with suggestive symptoms (suspicion of jaundice, and some hemorrhagic and parenchymatous lesions of the lungs and kidneys). This specimen showed no leptospira by dark-field examination. In experimental infection of guinea pigs with Leptospira icteroides the blood became infective in many instances 48 hours after inoculation, and was always infective after 72 hours. The liver and kidney become infective simultaneously with the blood. Detection of the organism by means of the dark-field microscope has seldom been accomplished before the 5th day. The organisms are most abundant on the 6th to the 7th day, but become fewer or completely disappear before death. In the meanwhile the number of organisms increases in the liver and kidney, from which they disappear as the jaundice and other symptoms become aggravated. When death occurs these organs seem to have lost most of the leptospira) and positive transfer by means of them is less certain. At the later stage of the disease the blood is often free from the organisms and ceases to be infective. Positive transmission with blood obtained from moribund animals is not impossible, however, even when no leptospira can be detected under the dark-field microscope.

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.

Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

2013 ◽  
Vol 62 (12) ◽  
pp. 1799-1806 ◽  
Author(s):  
Anne Holch ◽  
Hanne Ingmer ◽  
Tine Rask Licht ◽  
Lone Gram
Keyword(s):  
Listeria Monocytogenes ◽  
Guinea Pig ◽  
Food Processing ◽  
Guinea Pigs ◽  
Stop Codon ◽  
Fetal Liver ◽  
Fatal Case ◽  
Premature Stop Codon ◽  
Tissue Samples ◽  
Pregnant Mice

Listeria monocytogenes is an important food-borne bacterial pathogen and listeriosis can result in abortions in pregnant women. The bacterium can colonize food-processing environments, where specific molecular subtypes can persist for years. The purpose of this study was to determine the virulence potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10 % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlA m* (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas the maternofetal control was found in 6 % of fetal tissue samples. As the food-processing persistent strains carry a premature stop codon in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we hypothesize that listerial crossing of the placental barrier can occur by a mechanism that is independent of an interaction between E-cadherin and InlA.

Glucocorticoid receptors in the guinea pig

1978 ◽  
Vol 235 (3) ◽  
pp. R115-R120 ◽  
Author(s):  
A. J. Hodgson ◽  
J. W. Funder
Keyword(s):  
Guinea Pig ◽  
Inhibitory Activity ◽  
Guinea Pigs ◽  
Glucocorticoid Receptors ◽  
Metabolizing Enzymes ◽  
Pig Liver ◽  
Liver And Kidney ◽  
Guinea Pig Liver

In cytoplasmic fractions of liver and kidney prepared from adrenalectomized guinea pigs, tritiated dexamethasone ([3H]DM) is bound with a very low affinity (Kd 4 degrees C greater than or equal to 2 X 10(-7) M). By competition studies, the specificity of this binding was shown to be comparable with that for [3H]DM binding to glucocorticoid receptors in other species. In addition, cytoplasmic preparations from guinea pig liver and kidney appear to inhibit the binding of [3H]DM to rat glucocorticoid receptors under a variety of experimentally determined circumstances. It is proposed that such inhibitory activity may reflect a system of [3H]DM sequestration, perhaps by metabolizing enzymes with a high combining power for glucocorticoids. Both low affinity glucocorticoid receptors and avid binding to sites of metabolism may represent additive cellular bases for the apparent corticoresistance of the guinea pig.

scholarly journals ETIOLOGY OF YELLOW FEVER

1920 ◽  
Vol 31 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Guinea Pig ◽  
Beneficial Effect ◽  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Fatal Outcome ◽  
Clinical Manifestations ◽  
Immune Serum ◽  
Definite Advantage ◽  
Fever Patient

The use ot a polyvalent immune serum ot nign potency in tne treatment of an experimental infection of guinea pigs with Leptospira icteroides was found to be of definite advantage in checking the progress of the infection. When administered during the period of incubation the serum was found capable of completely preventing the development of the disease, although on subsequent examination hemorrhagic lesions of greater or less number and extent were found in the lungs of the guinea pigs which survived. Moreover, the serum modified the course of the disease and when used in the early stages of infection prevented a fatal outcome. Employed at a later stage, however, when jaundice and nephritis had been present for several days and the animal was near collapse, the serum had no perceptible beneficial effect. This was, of course, to be expected in view of the incidence of various pathological phases of this disease—nephritis, hepatitis, and other toxic symptoms in succession. In man the clinical manifestations are more gradual and distinct than in the guinea pig, yet the yellow fever patient whose temperature is sub-normal, and who has reached the stage of hemorrhages from the gums, nose, stomach, and intestines, and of uremia and cholemia, would seem to have little or no chance of deriving benefit from the use of a specific immune serum. This latter assumption would probably hold irrespective of the relation which Leptospira icteroides proves to have to the etiology of yellow fever.

Experimental Studies of Effects of Acupuncture on Enterochromaffin Cells: Guinea Pig Enterochromaffin Cell Count After Electro-Acupuncture

1980 ◽  
Vol 08 (03) ◽  
pp. 290-296 ◽  
Author(s):  
Yann-Ching Hwang
Keyword(s):  
Guinea Pig ◽  
Cell Count ◽  
Guinea Pigs ◽  
Experimental Studies ◽  
Treated Group ◽  
Enterochromaffin Cells ◽  
Longissimus Dorsi ◽  
Acupuncture Points ◽  
Enterochromaffin Cell

Guinea pig acupuncture points located on the back of the animal, cranial and caudal to the last rib in the muscular groove between longissimus dorsi and iliocostalis, were treated by electro-acupuncture (EA). In the duodenum, when compared with the control, the EA-treated group showed a significant decrease of its enterochromaffin (EC) cell count. However, the sham-treated group also had a lower EC cell count compared to the control. Decreased EC counts were also observed in the jejunum and colon in both EA and sham treated groups: however, they were not significant except in the sham-treated colon. The present study demonstrated that in the normal guinea pigs electro-acupuncture on certain points tends to cause a decrease of the EC cell count in some parts of the gut; however, such results cannot be completely attributed to the effect of acupuncture.

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 STUDIES UPON THE ETIOLOGY OF DENGUE FEVER

1924 ◽  
Vol 40 (6) ◽  
pp. 835-844 ◽  
Author(s):  
Charles W. Duval ◽  
William H. Harris
Keyword(s):  
Guinea Pig ◽  
Dengue Fever ◽  
Guinea Pigs ◽  
Human Case ◽  
Dark Field ◽  
Semisolid Medium ◽  
Original Culture ◽  
Human Material ◽  
Blood Specimens ◽  
Pass Through

We have described the cultivation of a minute organism, upon the special media devised by Noguchi for growing spirochetal organisms, that gives rise to pyrexial and leucocytic reactions in the guinea pig. The reaction in the animal following the injection of culture filtrate is identical with that induced by the inoculation of human dengue blood. While it is possible, it is hardly probable that the infection of animals with cultures of this microorganism several generations removed from the original is due to a mechanically transferred virus with which the visible microorganism cultivated became accidentally associated. Furthermore, it is unlikely that such a virus would remain viable and be carried over to subcultures in sufficient numbers to infect the animal. The microorganisms appear in culture as globoid bodies measuring from 0.1 to 0.3µ in diameter and are arranged singly, in pairs, and in short chains. They readily pass through the Berkefeld filter (N and V) and the filtrate gives rise to a characteristic reaction in the inoculated guinea pig. The filtrate yields in subplants the same globoid bodies of the original culture. Initial cultures have been obtained directly from the blood of the human case as well as from the blood of guinea pigs reacting to the human material. However, only early generations retain the degree of virulence necessary to cause the experimental reaction, the culture of remote generation failing to infect. As far as known this minute organism has characters in common with the globoid bodies of Flexner and Noguchi obtained from cases of poliomyelitis. In plasma semisolid medium the striking feature indicative of growth is colonization, which in itself serves to differentiate the opalescence of the medium occasioned by disintegration of the contained tissue. As regards the presence of spirochetal organisms in the blood of dengue fever, we may state that examination was made of the material from human cases and from. a large number of inoculated animals. Despite the most careful search with the dark-field microscope and repeated examinations of blood specimens stained by the best methods, we have been unable to find any demonstrable spiral organism in the blood of dengue patients or in the experimentally inoculated animal. The minute organism herein described is frequently present in cultures of the blood of human dengue and of animals inoculated with dengue material. The inoculation of the culture into guinea pigs produces a response comparable to that occurring in the human case, and that induced by the injection of human dengue blood in guinea pigs. While we are of the opinion that the anaerobic globular bodies described may bear etiological relationship to dengue, we realize that further proof and confirmation of our work are required to establish the connection.

scholarly journals EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER

1921 ◽  
Vol 34 (6) ◽  
pp. 525-535
Author(s):  
Peter K. Olitsky
Keyword(s):  
Staphylococcus Aureus ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Experimental Studies ◽  
The Body ◽  
Febrile Reaction ◽  
Cultivable Bacteria ◽  
Set Up ◽  
Typhus Fever ◽  
And Staphylococcus Aureus

The work reported in this paper relates to the bacteria which can be cultivated from the blood and spleen of guinea pigs at different stages of infection with the virus of typhus fever. The studies show that during the period of incubation and before the onset of fever no ordinary bacteria appear in the cultures, while on the 1st day of the febrile reaction different bacteria were found in 6 of 26 guinea pigs cultured; on the 2nd day, in 10 of 16; on the 3rd day, in 3 of 4; and on the 4th day in cultures of all of the 4 guinea pigs observed. The findings indicate that the virus of typhus fever is distinct from ordinary cultivable bacteria, and, as the disease set up by the virus progresses, the infected guinea pigs become subject to invasion by secondary or concurrent bacteria which thus induce a mixed infection. The bacteria which under the influence of the virus of typhus fever thus invade the body of the guinea pig are of several kinds, and vary not only among themselves, but also with the day of the fever on which the examination is made. Thus, on the 1st day of the fever Plotz' bacilli were recovered twice and anaerobic streptococci, proteus bacilli, aerobic diphtheroids, Gärtner type bacilli, and Staphylococcus aureus each once. On the 2nd day Plotz' bacilli were found four times, anaerobic streptococci three times, Gärtner type bacilli, aerobic diphtheroids, Bacillus welchii, aerobic Gram-positive diplobacilli, and Staphylococcus aureus each once. On the 3rd day Plotz' bacilli were recovered once, as were anaerobic streptococci and Grtner type bacilli. On the 4th day Staphylococcus aureus was found twice and Plotz' bacilli and Bacillus proteus each once. This variation in the kind of bacteria as well as the lack of predominance of one kind over another during the different stages of the febrile reaction in guinea pigs leads us to infer that they occur concurrently with the typhus virus. And since the more unusual of these organisms, the Plotz bacillus, the anaerobic streptococcus, the aerobic diphtheroid, and the diplobacillus are non-pathogenic for guinea pigs, while the more common bacteria such as the Gärtner type bacillus, Welch's bacillus, the proteus bacillus, and the staphylococci induce distinctive effects, and since all the bacteria could be suppressed without their reappearance in guinea pig passages of the virus containing them, we believe that they are independent and unrelated to the true virus of typhus fever.

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 29 (6) ◽  
pp. 585-596 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Gastrointestinal Tract ◽  
Guinea Pig ◽  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Febrile Reaction ◽  
Hemorrhagic Diathesis ◽  
Bile Pigments ◽  
Pathological Changes ◽  
Subcutaneous Inoculation

Studies are reported on the type of disease induced in guinea pigs, dogs, and monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs or other susceptible animals experimentally infected with Leptospira icteroides, and (2) with a pure culture of the organism. Particular attention has been given in these experiments to the clinical features of the experimental infection in the various animals and to the pathological changes resulting from the infection. The symptoms and pathological lesions induced in guinea pigs are much more pronounced than those observed in dogs or marmosets. The period of incubation is nearly the same in all three species, 72 to 96 hours with intraperitoneal or subcutaneous inoculation, and a day or more longer when the infection is induced percutaneously or per os. The febrile reaction in the guinea pig and marmoset is about the same; in the dog there is less fever. The amount of albumin, casts, and bile pigments in the urine is more abundant in the guinea pig and marmoset than in the dog, and these animals also appear on the whole to become more intensely icteric. The black or bilious vomit, however, though occurring frequently in dogs during life, is observed in the guinea pig and marmoset at autopsy. The hemorrhagic diathesis is most pronounced in guinea pigs, less so in marmosets, and least in dogs. In dogs) for example, subcutaneous hemorrhages almost never occur, and the lungs usually show only a few minute ecchymoses. The pleurse, pericardium, and other serous surfaces of the thorax and abdomen remain free from ecchymoses, which, however, with hyperemia, are very marked along the gastrointestinal tract. The symptoms and lesions observed in animals experimentally infected with Leptospira icteroides closely parallel those of human yellow fever. The pathological changes occurring in human cases of yellow fever are similar to those induced by inoculation in guinea pigs and marmosets and in respect to their intensity stand intermediate between those arising in the two animals mentioned.

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