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  4. 1938
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  4. 1938
Showing papers in "Journal of Experimental Medicine in 1938"
Journal Article•10.1084/JEM.67.1.25•
Two serological types of group b hemolytic streptococci with related, but not identical, type-specific substances

[...]

Rebecca C. Lancefield1•
Rockefeller University1
01 Jan 1938-Journal of Experimental Medicine
TL;DR: Among group B hemolytic streptococci one serological type previously described as homogeneous has been shown, instead, to contain two closely related types, distinguishable by reciprocal absorption experiments.
Abstract: 1. Among group B hemolytic streptococci one serological type previously described as homogeneous has been shown, instead, to contain two closely related types, distinguishable by reciprocal absorption experiments. These streptococci are designated Types Ia and Ib. 2. Homologous organisms in each case absorb all antibodies from their respective antisera, while organisms of the heterologous related type absorb only the antibody responsible for the cross reactions. Group B streptococci of other types do not absorb the antibodies responsible for the cross reactions between these two related types. The precipitin reaction and passive protection tests in mice were employed in this analysis. 3. The type-specific substance of Type Ia is a polysaccharide. Preliminary study indicates that this is also true of Type Ib. While no data are available concerning the chemical relationships of these substances, it seems probable that the two types elaborate polysaccharides, related chemically as well as serologically.

150 citations

Journal Article•10.1084/JEM.68.2.229•
Factors influencing the persistence of choriomeningitis virus in the blood of mice after clinical recovery

[...]

Erich Traub1•
Rockefeller University1
31 Jul 1938-Journal of Experimental Medicine
TL;DR: Mice infected in utero continued to carry choriomeningitis virus in the blood more regularly and in greater amount than suckling mice infected by contact, and carrier mice without exception had a high degree of immunity to intracerebral injection with virus, while other animals once infected but no longer carrying detectable amounts of virus inThe blood often showed an incomplete immunity that manifested itself in an accelerated, non-fatal reaction.
Abstract: Mice infected in utero continued to carry choriomeningitis virus in the blood more regularly and in greater amount than suckling mice infected by contact. This result may be due to the difference in tissue maturity at the time of infection: the more immature the tissues are when infected, the longer the virus appears to persist in them after maturation. A similar result was obtained with mice of different ages infected either by contact or by intranasal instillation of virus, in that the carrier state lasted longer in the younger animals. This cannot be attributed entirely to the difference in age, however, since young mice as a rule showed more severe symptoms than mature animals. It is possible, therefore, that the difference in the severity of the disease accounted in part for that in the duration of the infection. In mature mice infected experimentally as well as in some of the suckling mice infected by contact the severity of the disease was the determining factor, the infection persisting longest in those animals that showed the most severe reaction. The character of the virus used also appeared to influence the persistence of the virus in the blood. A strain of virus isolated in 1935 from an infected stock mouse and modified by intracerebral passage in mice (5) disappeared from the circulation more rapidly than the stock strain maintained by natural passage in the infected mouse stock. The guinea pig passage strain, however, which was obtained from the same mouse as the mouse passage virus but passed through guinea pigs by pad inoculation, persisted in the blood more frequently than the stock strain. Carrier mice without exception had a high degree of immunity to intracerebral injection with virus, while other animals once infected but no longer carrying detectable amounts of virus in the blood often showed an incomplete immunity that manifested itself in an accelerated, non-fatal reaction, presumably of an allergic nature. This observation does not prove, however, that the immunity always is an "infection immunity," since a high degree of resistance not associated with detectable amounts of virus in the blood and brain was produced by repeated injections with the mouse passage strain. Since the blood and the tissues of old carriers often contain large amounts of virus, it is very unlikely that their immunity is due to protective antibodies circulating in the blood or fixed in the tissue spaces. It rather appears that the susceptible cells of such animals are infected and that cells occupied by actively multiplying virus cannot be reinfected. The mechanism of this infection immunity as well as the immunity apparently not associated with infection requires further study.

140 citations

Journal Article•10.1084/JEM.68.3.353•
The effect of the pulse upon the formation and flow of lymph

[...]

Robert J. Parsons1, Philip D. McMaster1•
Rockefeller University1
31 Aug 1938-Journal of Experimental Medicine
TL;DR: The ears of rabbits were perfused with defibrinated rabbit's blood in such a way that pulsation could be imparted to the perfusate or withheld from it at will, causing a slight flow of lymph in ears that were becoming edematous, whereas when it was pulsatile the lymph flow was enormous.
Abstract: The ears of rabbits were perfused with defibrinated rabbit's blood in such a way that pulsation could be imparted to the perfusate or withheld from it at will. In the absence of pulsation there was almost no lymph flow, whereas when it was present lymph flow was rapid despite the fact that the "systolic" pressure of the perfusate never exceeded the constant pressure in the non-pulsatile instances and the volume flow was far less. Non-pulsatile perfusion led to a slight flow of lymph in ears that were becoming edematous, whereas when it was pulsatile the lymph flow was enormous. The pulse exercises an influence to move fluid into the lymphatics and along them.

136 citations

Journal Article•10.1084/JEM.68.2.147•
An unidentified virus producing acute meningitis and pneumonitis in experimental animals.

[...]

Thomas Francis1, T. P. Magill1•
Rockefeller Foundation1
31 Jul 1938-Journal of Experimental Medicine
TL;DR: Cross immunity tests have failed to yield any evidence that the new agent is immunologically related to either of the aforementioned viruses, so the name virus of acute meningopneumonitis is suggested.
Abstract: An infectious agent is described which belongs apparently to the class of filtrable viruses, but which, on the basis of the evidence at hand, is not to be identified with any virus previously described. The virus has multiple tropisms and is pathogenic for mice, ferrets, and monkeys of both M. rhesus and M. cynomolgos species. Intranasal infection of mice and ferrets causes extensive pneumonic lesions of fatal severity. Intracerebral inoculation of the virus produces in monkeys a lymphocytic choriomeningitis from which the animal recovers, while in mice a rapidly fatal choriomeningitis is produced. Fatal paralysis occurs in a moderate proportion of mice which receive the virus by intraperitoneal or subcutaneous routes, while the remainder become immune to the intracerebral test but not to the intranasal test. Subcutaneous inoculation of mice, monkeys, ferrets, rabbits, and guinea pigs causes local granulomatous induration of the skin with enlargement of the regional lymph nodes. The virus was repeatedly recovered in 1936 from ferrets inoculated with throat washings of patients suffering from an epidemic disease clinically indistinguishable from epidemic influenza. It is impossible, however, to conclude whether the virus is of ferret or human origin. Although possessing many features in common with the virus of lymphocytic choriomeningitis and the virus of lymphogranuloma inguinale, cross immunity tests have failed to yield any evidence that the new agent is immunologically related to either of the aforementioned viruses. For purposes of identification the name virus of acute meningopneumonitis is suggested.

121 citations

Journal Article•10.1084/JEM.68.3.299•
The effect of sex hormones on the renal excretion of electrolytes.

[...]

George W. Thorn1, Lewis L. Engel1•
Johns Hopkins University1
31 Aug 1938-Journal of Experimental Medicine
TL;DR: It is indicated that the effect of the sex hormones on the renal excretion of electrolytes was not necessarily mediated through the suprarenal gland, and with the possible exception of progesterone none of the compounds studied was effective in prolonging the life of suprarenalsized male dogs.
Abstract: In normal male dogs subcutaneous injections of progesterone, estrone, α-estradiol or testosterone propionate were followed by a decreased renal excretion of sodium and chloride. The compounds differed markedly in their potency and in the duration of the effect following a single subcutaneous injection. The injection of estrone, α-estradiol or testosterone propionate was followed by a decreased renal excretion of inorganic phosphorus and total nitrogen. On the day of injection a slight increase in the renal excretion of potassium frequently followed administration of progesterone, estrone, α-estradiol or testosterone propionate. Experiments on suprarenalectomized dogs indicated that the effect of the sex hormones on the renal excretion of electrolytes was not necessarily mediated through the suprarenal gland. With the possible exception of progesterone none of the compounds studied was effective in prolonging the life of suprarenalectomized male dogs.

120 citations

Journal Article•10.1084/JEM.68.3.335•
Studies on the antigenic structure of some mammalian spermatozoa

[...]

Werner Henle1, Gertrude Henle1, Leslie A. Chambers1•
University of Pennsylvania1
01 Sep 1938-Journal of Experimental Medicine
TL;DR: By means of absorption technique applied to homologous spermatozoal sera, head-specific and tail-specific antigens could be demonstrated and a heat-stable antigen was found to be common to both heads and tails.
Abstract: 1. A method has been described for separation of heads and tails of mammalian spermatozoa. 2. By means of absorption technique applied to homologous spermatozoal sera, head-specific and tail-specific antigens could be demonstrated. Both are heat-labile. 3. A heat-stable antigen was found to be common to both heads and tails. This substance is species-specific. 4. Antibodies against the head- and tail-specific antigens led to two different types of agglutination as shown by the slide method. 5. Using heterologous antisera against spermatozoa three different cross-reacting antigens could be observed, two in the heads, one in the tails. 6. One of the head-antigens is not active in the native cell; it comes to action only after breaking the cell. Antibodies against this substance were not found in antisera against native bull spermatozoa but were formed when vibrated spermatozoa or heads were injected into rabbits. 7. The cross-reactions can be removed from an antiserum leaving the head- as well as the tail-specific reaction intact.

105 citations

Journal Article•10.1084/JEM.67.2.201•
Influence of host factors on neuroinvasiveness of vesicular stomatitis virus : iii. effect of age and pathway of infection on the character and localization of lesions in the central nervous system.

[...]

Albert B. Sabin1, Peter K. Olitsky1•
Rockefeller University1
01 Feb 1938-Journal of Experimental Medicine
TL;DR: In Vol.
Abstract: It will be well to restate the main problem at this point and to examine how far the accumulated data can help to elucidate it. The problem is this: Why are old mice generally resistant to all forms of peripheral inoculation of vesicular stomatitis virus when intracerebral injection is equally fatal for mice of all ages? The results of experiments in which the presence of virus was demonstrated by animal passage suggested that the reason can perhaps be found in (a) the different mechanisms of virus progression after intracerebral and peripheral injection, and (b) the development with age of localized barriers capable of halting the spread of virus (1, 2). The present study sought histological evidence for the nature of virus progression and for the changes observed in the older animals. The results clearly demonstrate that after intracerebral injection virus spreads along an open system, the lesions being distributed almost entirely in contiguity with the ventricles and their extensions, while after peripheral inoculations the evidence points to progression of the virus in a closed system of neurons and their processes, at least in the stage preceding neuronal necrosis, the distribution of lesions depending upon the central connections of the primary neurons connected with the inoculated site. Thus, in young mice, nasal instillation of the virus was followed by necrosis of a long chain of neurons, starting with those in the olfactory mucosa and progressing through specific zones of the olfactory pathway, pursuing the same order in which the various regions are known to have their major connections with one another. It is important to note that after nasal instillation the apparent lesions were present where the cell bodies of the neurons are situated, and not along the tracts connecting one group of neurons with another, which accounts for the lack of contiguity between the affected zones and the normal appearing, intervening areas. The assumption that the primary progression of the virus in this case occurs in a closed system is based on the absence of lesions in unrelated areas contiguous to those which are necrotic and to the tracts which connect one affected zone with another. Additional evidence for the assumption that the initial dissemination of peripherally injected virus is in a closed system is found in the decussating optic nerve pathway primarily pursued by the intraocularly injected virus. The progression of the virus along this decussating pathway was indicated in the experimental data obtained on mice 21 days or older, while in younger animals the spread of virus was so rapid and diffuse that the pathways along which it might have occurred remained obscure (2). In the present study, in which 15 day old mice were used, the lesions in the retinal neurons and the constant involvement of only the contralateral superior colliculus left little doubt that the primary spread of the virus, even in these very young animals, must have occurred within the retinal neuron processes (axons) which decussate in the optic chiasm (in the mouse, as in the rat, very few of these go to the homolateral side) and synapse chiefly with the neurons of the contralateral superior colliculus and also, apparently to a lesser extent, with those of the contralateral external geniculate body, where lesions were also demonstrated. Virus spreading in the optic nerve along the perineural subarachnoid space would be found at the base of the brain at the optic chiasm; virus extending along the interstitial spaces in the optic nerve should involve not only the nuclei of both sides of the optic pathway but also non-optic structures, such as the medial geniculate bodies, posterior colliculi, etc., by means of the commissures of von Gudden and of Meynert, whose fibers course through the chiasm. The highly specific localization observed in the present study is best accounted for by progression along the suggested closed pathway. Hurst (10) observed that poliomyelitis virus, after injection into the left sciatic nerve, may, after invading the lumbar cord, be found first in the contralateral motor cortex or thalamus and he suggested that this was evidence of progression along a decussating pathway and in favor of the axonal hypothesis of virus spread. It was not shown, however, that this particular localization was specifically related to the introduction of virus in the left sciatic nerve, or that it could be reversed by inoculating the sciatic nerve of the opposite side. The hypothesis proposed by Hurst, however, finds support in the present instance for (a) the superior colliculi never showed lesions after intracerebral, intranasal, or intramuscular inoculations, and (b) necrosis was produced in either the right or the left superior colliculus, depending on whether the virus was injected into the left or right eyes. The localization of lesions after injection of virus into the muscles of one leg indicated that in the young the invasion occurred along the local peripheral nerves, especially the motor fibers (neurons destroyed in the lumbar cord with those in the spinal ganglia intact), after a primary attack on the muscle itself. The only other lesions found at a late stage were in the reticular substance of the medulla, the olfactory portions of the brain appearing entirely normal. In this respect the mechanism of progression of intramuscularly injected vesicular stomatitis virus differs from that of eastern equine encephalomyelitis and pseudorabies viruses similarly injected into mice of the same age and breed: the former (E.E.E.) invades the central nervous system in the majority of instances, by being eliminated on the nasal mucosa and then along the olfactory pathways (18), while the latter appears to employ chiefly the local sensory fibers, attacking primarily the neurons in the spinal ganglia (unpublished observations). Because the CNS of old mice remain for the most part susceptible to vesicular stomatitis virus (although definite evidence of resistance to necrosis of the neurons was observed), and because after intracerebral injection the virus has been shown to spread in an open (ventricular) system, it is clear why young and old mice are equally susceptible to inoculation by this route. After peripheral inoculation, however, it has been amply demonstrated by experimental and histological methods that the spread of this virus begins and continues, at least until the cells disintegrate, in a closed system within the neurons and their processes and apparently also across the synapses. The halting of the virus somewhere in the anterior rhinencephalon after nasal instillation in resistant mice (1) would appear to be due to an arrest in an insusceptible neuron or an impenetrable synapse somewhere in the chain, and to the failure of the affected neurons to disintegrate (no lesions were found in the CNS of these mice) and thus to liberate the virus into the open system. After intramuscular injection, on the other hand, the virus encounters a different kind of muscle cell in the old mouse, and its inability to invade the nerves may perhaps be bound up with its demonstrated inability to attack and multiply in these changed muscle cells, although the role of a possible alteration in the terminal nerve endings themselves is not yet clear. After intraocular injection, the virus fails to affect visibly the retinal neurons of resistant old mice and the further invasion of the CNS is inhibited. The resistance of old mice to peripheral inoculations of vesicular stomatitis virus thus appears to be the result of (a) changes produced by age not in the whole animal but in certain specific, isolated structures, and (b) the special mode of progression of peripherally injected virus. It may be of interest to point out two phenomena which may perhaps be related to the one investigated in the present study. Tobacco mosaic virus has been found to produce different types of disease in certain plants of different ages; thus a widespread, systemic necrosis leads to the death of young Nicotiana rustica plants, while in old plants it is possible to produce necrotic foci in many parts of the plant by direct inoculation, although generalization does not occur from an isolated focus as it does in young specimens (19). In other words, age apparently does not change the whole plant, but it does transform something which allows the virus to spread easily from one site to another. MacNider (20) has observed that dogs which survive a severe type of hepatic injury from uranium, repair this injury with a special type of atypical, epithelial cell and become resistant not only to secondary intoxications by uranium but also by chloroform; he has also found that this change in epithelial cell type may be acquired as a product of senility, and that when it develops it imparts to the liver a degree of resistance to chloroform comparable to that induced by a process of repair following a severe hepatic injury from uranium nitrate.

103 citations

Journal Article•10.1084/JEM.68.3.377•
The effect of the pulse on the spread of substances through tissues.

[...]

Philip D. McMaster1, Robert J. Parsons1•
Rockefeller University1
01 Sep 1938-Journal of Experimental Medicine
TL;DR: The pulsation of blood vessels in the ear of the rabbit greatly increases the rate of the spread of dye introduced into the subcutaneous tissue, and a rapid interstitialSpread of dye occurs in tissues becoming edematous while perfused with a pulsatile flow of blood.
Abstract: The pulsation of blood vessels in the ear of the rabbit greatly increases the rate of the spread of dye introduced into the subcutaneous tissue. The appearance of edema in tissues perfused at a constant pressure leads to very little increase in the rate of dye spread. By contrast, a rapid interstitial spread of dye occurs in tissues becoming edematous while perfused with a pulsatile flow of blood. The significance of these facts is discussed.

86 citations

Journal Article•10.1084/JEM.67.6.857•
The agglutination of plasmodium knowlesi by immune serum

[...]

Monroe D. Eaton1•
Rockefeller Foundation1
01 Jun 1938-Journal of Experimental Medicine
TL;DR: A specific agglutination of Plasmodium knowlesi detectable both by macroscopic and by microscopic methods is described, and the relation of these observations to the mechanism of active and passive immunity in monkey malaria is discussed.
Abstract: A specific agglutination of Plasmodium knowlesi detectable both by macroscopic and by microscopic methods is described. Agglutinins for Plasmodium knowlesi appear in the sera of monkeys between 15 and 45 days after the onset of the infection and become progressively stronger as the malarial infection gradually subsides. Agglutinins persist in the sera of chronically infected animals for a year or longer. The sera of animals which have been repeatedly superinfected agglutinate parasites at dilutions as high as 1:1,000. Sera from normal monkeys, from monkeys acutely ill with malaria, and from monkeys chronically infected with a different species of malarial parasite (Plasmodium inui) do not agglutinate Plasmodium knowlesi. Immune serum agglutinates mature intracellular or extracellular parasites but does not agglutinate unparasitized cells or cells containing immature parasites. The relation of these observations to the mechanism of active and passive immunity in monkey malaria is discussed.

84 citations

Journal Article•10.1084/JEM.68.6.789•
Studies on the nasal histology of epidemic influenza virus infection in the ferret : i. the development and repair of the nasal lesion

[...]

Thomas Francis1, C. H. Stuart-Harris1•
Rockefeller Foundation1
01 Dec 1938-Journal of Experimental Medicine
TL;DR: The nasal histology in normal ferrets and in ferrets during and after infection with epidemic influenza virus is made and the respiratory mucosa is substantially normal in structure 1 month after infection.
Abstract: A study has been made of the nasal histology in normal ferrets and in ferrets during and after infection with epidemic influenza virus. During the acute stage of infection the respiratory epithelium of the nasal mucous membrane undergoes necrosis with desquamation of the superficial cells and exudation into the air passages, and an inflammatory reaction occurs in the submucosa. Repair begins on the 4th day after infection, and from the 6th to the 14th day the respiratory area is covered successively by a transitional, a stratified squamous, and finally a stratified columnar epithelium. By the 21st day after infection the epithelium has been largely restored to normal but repair in the submucosa and cartilage is still in progress. The respiratory mucosa is substantially normal in structure 1 month after infection although minor abnormalities of cellular arrangement and type can still be distinguished.

77 citations

Journal Article•10.1084/JEM.68.4.529•
The carcinogenic effect of a papilloma virus on the tarred skin of rabbits : ii. major factors determining the phenomenon: the manifold effects of tarring.

[...]

John G. Kidd1, Peyton Rous1•
Rockefeller University1
30 Sep 1938-Journal of Experimental Medicine
TL;DR: The Shope papilloma virus elicits carcinomas forthwith, as well as papillomas in great variety, when it is distributed by way of the blood stream to the tarred epidermis of domestic rabbits.
Abstract: A considerable variety of tumors, both benign and malignant, result from the localization of the rabbit papilloma virus in skin which has been prepared by repeated tarrings They appear only in individuals highly susceptible to the action of the virus, and are more likely to be engendered by highly pathogenic inocula No evidence has been found that differences in the potentialities of the virus entities are responsible for the diversity of the growths This is referable to changes in the epidermal cells; and much more preliminary tarring is required to produce these changes than suffices to cause localization of the virus out of the blood stream with a resulting papillomatosis of the ordinary sort The character of the individual anomalous tumors depends in some degree upon the extent of the preparatory changes in the cells, malignant growths being more frequent when the epidermis has been tarred for a relatively long period All are focal or punctate in origin, and they exhibit their peculiar characters from the first, none being due to secondary alterations in ordinary papillomas Tarring after the virus has localized in the epidermis does not significantly increase their number They are the outcome of the state of the cells at the time of virus infection Tarring exerts important influences in addition to changing the cells in such a way that unusual tumors result from the action of the virus The procedure is notably effective in determining localization of the virus out of the blood stream; enables it to produce growths when otherwise it would not do so though present in the tarred skin; stimulates the proliferation of the tumors engendered; makes them disorderly and aggressive; and hastens the anaplasia of such of them as are malignant It has similar effects upon the tar tumors, as will be demonstrated in a subsequent paper
Journal Article•10.1084/JEM.67.5.691•
Uterine adenomata in the rabbit : i. clinical history, pathology and preliminary transplantation experiments.

[...]

Harry S. N. Greene1, John A. Saxton1•
Rockefeller University1
01 May 1938-Journal of Experimental Medicine
TL;DR: Intraocular transplantation of the tumor has been successful, and at the present time the growth has been carried through 6 generations by serial transfer.
Abstract: 83 cases of an adenomatous tumor of the uterine mucosa have been observed in a colony of rabbits during the past 4 years The results of a clinical and pathological study of the tumor, together with a description of transplantation experiments are included in the present report. The clinical histories of tumor bearing animals are similar in all cases. Discovery of the tumor is preceded by a long period of reproductive disturbance, and its subsequent course is one of slow, continuous growth which has terminated in death with metastasis in all animals held under observation for longer than 1 year. Microscopically, the tumor shows an atypical alveolar structure, and its characteristics closely resemble those of an adenocarcinoma of the uterine fundus in women. Pathological changes similar to those observed in mice after treatment with estrogenic substances occur in the thyroid, suprarenal, pituitary and mammary glands. Intraocular transplantation of the tumor has been successful, and at the present time the growth has been carried through 6 generations by serial transfer.
Journal Article•10.1084/JEM.68.3.413•
Molecular weight, electrochemical and biological properties of tuberculin protein and polysaccharide molecules.

[...]

Florence B. Seibert1, Kai O. Pedersen1, Arne Tiselius1•
University of Pennsylvania1
31 Aug 1938-Journal of Experimental Medicine
TL;DR: Page 435, Table X, third entry under s 20, for 1.2 read 3.3.
Abstract: Studies have been made by means of sedimentation in the ultracentrifuge, and by diffusion and electrophoresis, to determine the molecular weights and homogeneity of the tuberculin protein and polysaccharide molecules as found in their natural state in the unchanged filtrates from culture media after growth of tubercle bacilli. These results have been compared with data obtained on fractions isolated by chemical procedures from them or from old tuberculin. By means of electrophoresis in the Tiselius apparatus it was possible to separate the protein from the polysaccharide, as these two fractions occur naturally in the original culture medium filtrates of acid-fast bacilli. The protein from the bovine strain of bacillus proved to be homogeneous in sedimentation (S(20) = 1.6), diffusion (D(20) = 12.0) and electrophoresis, with a molecular weight of about 10,000. The tuberculin polysaccharide isolated in electrophoresis appeared to be practically the same in sedimentation and in precipitin reaction as the polysaccharide isolated by chemical procedure. The latter proved to be homogeneous in sedimentation (S(20) = 1.6) and diffusion (D(20) = 11.0) with a molecular weight of about 9000. A practically homogeneous protein was isolated from the culture filtrate of the human tubercle bacillus H 37 by fractional ammonium sulfate precipitation, with a molecular weight of 32,000 (S(20) = 3.3; D(20) = 8.2). It was electrochemically homogeneous, with an isoelectric point at pH 4.3 and an isoionic point at pH 4.7. It could be dried or frozen with no loss in homogeneity. It was highly antigenic in the precipitin reaction and produced the anaphylactic type of local skin reaction in tuberculous guinea pigs, in contrast to the true tuberculin type of reaction caused by a purified PPD fraction. Furthermore death resulted in tuberculous guinea pigs from intracutaneous injection of exceptionally small amounts. A protein with molecular weight of about 17,000 was isolated from the filtrate from cultures of the timothy bacillus. The nucleic acid originally occurring in old tuberculin (OT) seems to be responsible for the high electrochemical mobility observed. From OT and the PPD made from it, potent but non-antigenic molecules of 16,000 and 9000 weight and with a low content of nucleic acid were isolated. With increase in size these deviated much from the normal compact spherical shape, and aggregation was evident from the tendency toward gel formation. The smallest molecule (9000) was homogeneous (S(20) = 1.0; D(20) = 10.0) and had lost some tuberculin potency.
Journal Article•10.1084/JEM.67.5.725•
Statistical studies of the nature of the infectious unit of vaccine virus

[...]

Robert F. Parker1•
Case Western Reserve University1
01 May 1938-Journal of Experimental Medicine
TL;DR: From the results here reported, it appears that other factors are responsible for the altered character of the lesion than the ability of the virus to establish a foothold in the animal organism.
Abstract: A method has been described by which it is possible to estimate the number of particles of vaccine virus which are required to cause infection in the rabbit skin. The method consists essentially in performing a series of intradermal inoculations in rabbits of suitably diluted virus suspensions. The percentage of inoculations at each dilution giving rise to lesions is observed, and the data are subjected to appropriate statistical analysis. Several strains of vaccine virus, differing in their characteristics, have been studied with the following results. Infection with the New York City Board of Health virus appears to follow the injection of a single particle of virus. The same is true for the strain derived from it but cultured in a chick embryo-Tyrode solution medium for a prolonged period. This strain, as has been noted, has largely lost its ability to cause extensive necrosis in the rabbit skin, and causes generalized infection only exceptionally. From the results here reported, it appears that other factors are responsible for the altered character of the lesion than the ability of the virus to establish a foothold in the animal organism. In this respect the cultured appears to be the equal of the original passage virus. Similarly the Noguchi strain of virus is apparently capable of infecting, if a single virus particle is properly introduced.
Journal Article•10.1084/JEM.68.4.513•
A pyogenic filterable agent in the albino rat

[...]

William H. Woglom1, Joel Warren•
Columbia University1
01 Oct 1938-Journal of Experimental Medicine
TL;DR: A filterable agent resembling the viruses was encountered in sarcoma 39, a propagable neoplasm of the white rat, and has now been maintained in this species for 28 passages over a period of some 7 months without appreciable loss in virulence.
Abstract: A filterable agent resembling the viruses is described. It was encountered in sarcoma 39, a propagable neoplasm of the white rat, and has now been maintained in this species for 28 passages over a period of some 7 months without appreciable loss in virulence. Its chief effect is the production of large abscesses in an animal species comparatively resistant both to viral diseases and suppuration. The white mouse is more susceptible than the white rat, the rabbit less so, and the guinea pig highly resistant. The agent has been repeatedly recovered from sarcoma 39 treated in special ways, but under the ordinary circumstances of routine transplantation it does not manifest itself. As yet there is no certainty on where it came from or how it maintains itself under natural conditions.
Journal Article•10.1084/JEM.68.4.607•
Ultracentrifugation studies on the elementary bodies of vaccine virus ii. the influence of sucrose, glycerol, and urea solutions on the physical nature of vaccine virus

[...]

Joseph E. Smadel1, Edward G. Pickels1, Theodore Shedlovsky1•
Rockefeller University1
30 Sep 1938-Journal of Experimental Medicine
TL;DR: Throughout the article by Drs.
Abstract: Ultracentrifugal studies of the CL dermal strain of vaccine virus warrant the following conclusions: 1. When suspended in increasing concentrations of sucrose, glycerol, or urea solutions, elementary bodies of vaccinia show variations in sedimentation rate which indicate changes in the density or size of the particles. For a given change in the density of the medium these changes are smallest with sucrose and most marked with urea. The normal rate of sedimentation of Paschen bodies may be restored by resuspending them in dilute buffer solution. 2. The density of elementary bodies of vaccinia suspended in dilute buffer solutions is estimated to be 1.16 gm. per cc. Higher values for the density are found if the particles are suspended in solutions containing sucrose, glycerol, or urea. In 53 per cent sucrose, for example, the density is 1.25 gm. per cc. 3. Paschen bodies appear to be quite permeable to water and urea, less so to glycerol, and only slightly, if at all, to sucrose. 4. The increased density of the elementary bodies of vaccinia in sucrose solutions may be accounted for by an osmotic extraction of water from the particles. On this basis the water which can be thus extracted corresponds to at least a third of the original volume of the particles.
Journal Article•10.1084/JEM.67.2.181•
Quantitative studies on antibody purification : ii. the dissociation of antibody from pneumococcus specific precipitates and specifically agglutinated pneumococci.

[...]

Michael Heidelberger1, Elvin A. Kabat1•
NewYork–Presbyterian Hospital1
31 Jan 1938-Journal of Experimental Medicine
TL;DR: The salt dissociation and barium hydroxide-barium chloride methods are extended to the preparation of highly purified antibody solutions from specific precipitates derived from Type III and Type VIII antipneumococcus horse sera and a low grade polyvalent bovine serum.
Abstract: 1. The salt dissociation and barium hydroxide-barium chloride methods are extended to the preparation of highly purified antibody solutions from specific precipitates derived from Type III and Type VIII antipneumococcus horse sera and a low grade polyvalent bovine serum. Analytically pure precipitin (agglutinin) was obtained from the last, and Types I, II, and III antibodies were separated. 2. Difficulties connected with the application of the methods to Type I antipneumococcus rabbit sera are described, as is also the purification of antibody from low grade pig and sheep sera. 3. The dissociation of antibody by both methods from Type I pneumococci agglutinated in antisera produced in the horse, rabbit, pig, and sheep, is described and its advantages discussed. 4. Certain theoretical aspects of the work are also discussed.
Journal Article•10.1084/JEM.68.6.923•
Nutritional cytopenia (vitamin M deficiency) in the monkey.

[...]

William C. Langston1, William J. Darby1, Carroll F. Shukers1, Paul L. Day1•
University of Arkansas at Little Rock1
01 Dec 1938-Journal of Experimental Medicine
TL;DR: It is evident that yeast and liver extract contain a substance essential to the nutrition of the monkey which is not identical with any of those factors of the vitamin B complex that have been chemically identified, and the term vitamin M is proposed for this factor which prevents nutritional cytopenia in the monkey.
Abstract: Young rhesus monkeys (Macaca mulatta) were given a diet containing casein, polished rice, whole wheat, salt mixture, sodium chloride, cod liver oil, and ascorbic acid. They developed a syndrome characterized by anemia, leukopenia, and loss of weight. Ulceration of the gums and diarrhea were common, and death occurred between the 26th and 100th day. 4 monkeys were given the deficient diet supplemented with 1 mg. of riboflavin daily, and these developed the characteristic signs and died. in periods of time similar to the survival of monkeys receiving the deficient diet alone. Nicotinic acid, either alone or in combination with riboflavin and thiamin chloride, failed to alter appreciably the course of the deficiency manifestations. Thus, it is evident that this nutritional cytopenia is not the result of a deficiency of vitamin B, riboflavin, or nicotinic acid. The deficient diet supplemented with either 10 gm. of dried brewers' yeast or 2 gm. of liver extract (Cohn fraction G) daily supported good growth, permitted normal body development, and maintained a normal blood picture over long periods. It is obvious that yeast and liver extract contain a substance essential to the nutrition of the monkey which is not identical with any of those factors of the vitamin B complex that have been chemically identified. We have proposed the term vitamin M for this factor which prevents nutritional cytopenia in the monkey.
Journal Article•10.1084/JEM.68.6.803•
Studies on the nasal histology of epidemic influenza virus infection in the ferret : ii. the resistance of regenerating respiratory epithelium to reinfection and to physicochemical injury.

[...]

C. H. Stuart-Harris1, Thomas Francis1•
Rockefeller Foundation1
31 Oct 1938-Journal of Experimental Medicine
TL;DR: Serological studies at the time of reinfection, 4 months or more after the previous attack, indicate that a relation exists between the height of antibody titer and resistance, and the degree of immunity is probably a product of serological immunity and the rate of tissue repair.
Abstract: Because of the marked morphological abnormality of the nasal respiratory epithelium in ferrets recovering from epidemic influenza virus infection, attempts were made to determine whether the anatomical changes were associated with functional changes in the epithelial cells. It was found that on the 7th or 8th day after infection, at which time an immature transitional type of epithelium covers the respiratory area, the cells are resistant not only to reinfection with influenza virus but to a severe physicochemical stimulus supplied by iontophoresis or prolonged irrigation with zinc sulfate. Later, as the ciliated columnar cells return, susceptibility to physicochemical injury returns although resistance to influenza virus persists. The ciliated columnar cells are the ones which are damaged by the physicochemical agent while the deeper cells in the regenerating area remain unaffected. 5 weeks after infection the epithelium is anatomically normal but tissue resistance to zinc sulfate is still present to some degree as evidenced by foci of undamaged cells remaining after ionization. The olfactory epithelium which is undamaged by the PR8 strain of epidemic influenza virus also becomes resistant to ionization after infection. As soon as the respiratory epithelium exhibits any loss of resistance to zinc sulfate the chemical produces complete necrosis of the olfactory area. The refractory state to physicochemical agents exhibited by the regenerating nasal mucosa of the ferret after influenza virus infection is thought to be a non-specific resistant state, significant for a time at least, in the mechanism of immunity to influenza virus.
Journal Article•10.1084/JEM.68.6.831•
Plasma prothrombin: effect of partial hepatectomy.

[...]

E. D. Warner1•
University of Iowa1
31 Oct 1938-Journal of Experimental Medicine
TL;DR: The decrease in prothrombin incident to partial hepatectomy supports the thesis that the liver is concerned in the manufacture of plasma prothROMbin.
Abstract: Extirpation of a large portion of the liver in rats results in a marked decrease in the plasma prothrombin. The plasma prothrombin level gradually returns to normal during the period required for restoration of the liver to its normal weight. The decrease in prothrombin incident to partial hepatectomy supports the thesis that the liver is concerned in the manufacture of plasma prothrombin.
Journal Article•10.1084/JEM.67.1.159•
Studies on the relationship of the sex hormones to infection : i. the effect of the estrogenic and gonadotropic hormones on vaccinia and the spreading factor.

[...]

Douglas H. Sprunt1, Sara McDearman1, James S. Raper1•
Duke University1
01 Jan 1938-Journal of Experimental Medicine
TL;DR: The essential findings of these experiments may be summarized as follows: the estrogenic hormone after being given for 1 week slows up the spread of India ink but allows it to reach and exceed a normal spread after 24 hours.
Abstract: The essential findings of these experiments may be summarized as follows: The estrogenic hormone after being given for 1 week slows up the spread of India ink but allows it to reach and exceed a normal spread after 24 hours. After injections of the estrogenic hormone for 3 weeks the spread of India ink is much less than in the control animals. The resistance of the rabbit to vaccinia is increased if the rabbit has been castrated and then given the estrogenic hormone for a period of 3 weeks before being vaccinated. At the present time nothing can be said about the action of the gonadotropic hormone on India ink, as the experiments did not agree.
Journal Article•10.1084/JEM.67.4.551•
The course of virus-induced rabbit papillomas as determined by virus, cells, and host

[...]

John G. Kidd1•
Rockefeller University1
01 Apr 1938-Journal of Experimental Medicine
TL;DR: An experimental analysis of the factors responsible for the observed differences in the course of virus-induced papillomas of the rabbit has shown that some are referable to the virus, others to the cells, and yet others to host influences.
Abstract: An experimental analysis of the factors responsible for the observed differences in the course of virus-induced papillomas of the rabbit has shown that some are referable to the virus, others to the cells, and yet others to host influences The interplay of these factors affords enlightening illustration of the nature of the cell-virus relationship in virus-induced tumors Retrogression of the rabbit papillomas appears to be consequent on a generalized resistance of host origin, elicited by and directed against the proliferating, virus-infected cells
Journal Article•10.1084/JEM.67.2.229•
Influence of host factors on neuroinvasiveness of vesicular stomatitis virus: iv. variations in neuroinvasiveness in difierent species.

[...]

Albert B. Sabin1, Peter K. Olitsky1•
Rockefeller University1
31 Jan 1938-Journal of Experimental Medicine
TL;DR: It was clear that virus so inoculated must spread differently from that which reaches the brain by the olfactory pathway, since minimal amounts of virus injected intracerebrally were shown to be disseminated quickly through the entire brain, killing old as well as young mice.
Abstract: Peripheral inoculation of vesicular stomatitis virus is constantly followed by myelitis or encephalitis in young mice, but not in young (or old) guinea pigs The cause of this variation was elucidated by investigating the fate of the virus after inoculation by a number of different routes Direct intracerebral injection of minimally infective amounts of virus was found to be equally fatal for young mice and young guinea pigs, indicating that the central nervous system as a whole was as easily injured by the virus in one species as in the other The events following nasal instillation of the virus varied in young and old guinea pigs While there appeared to be a transitory multiplication of virus in the nasal mucosa of both young and old, the central nervous system was regularly invaded only in the young In these, virus was first found only in the anterior rhinencephalon; later it spread to the piriform and hippocampal (olfactory regions) but not to the neopallial portions of the cortex, and the only other area to exhibit virus was the diencephalon (including the pars optica hypothalami), where its further progression was apparently arrested Absence of central nervous system disease following inoculation into sites supplied by spinal nerves (eg sciatic) was found to be due to inability of the virus to invade the nerves Since direct intrasciatic inoculation frequently led to a fatal ascending myelitis, it was evident that the central nervous system could be invaded along the spinal nerves, and that they did not constitute the main barrier Furthermore, since multiplication of virus was demonstrated in tissues supplied by the spinal nerves, a process of elimination made it seem possible that the specialized, terminal nerve endings might be the structures which prevent the progression of the virus from the infected tissues to the axons and hence also to the central nervous system 7 day old guinea pigs (or guinea pigs as a species) were thus found to possess much the same type of barriers to the progression of peripherally inoculated vesicular stomatitis virus as are acquired by mice at a considerably later age In a discussion of the present data, they have been correlated with known variations in neuroinvasiveness of other viruses and their bearing on the nature of inapparent or subclinical infections of the central nervous system has been considered
Journal Article•10.1084/JEM.67.1.61•
The preservation of virulent treponema pallidum and treponema pertenue in the frozen state; with a note on the preservation of filtrable viruses

[...]

Thomas B. Turner1•
Rockefeller Foundation1
01 Jan 1938-Journal of Experimental Medicine
TL;DR: When frozen and maintained at this temperature TrePonema pallidum and Treponema pertenue exhibited normal morphology and motility and their virulence for rabbits was not appreciably altered after periods of at least 1 year, while the viruses of human influenza, yellow fever, and spontaneous encephalomyelitis of mice showed substantially the same titer after 6 months as before freezing.
Abstract: 1. A simple method for freezing and maintaining tissue specimens in a mixture of solid carbon dioxide and 95 per cent ethyl alcohol at a temperature approximating -78 degrees C. is described. 2. When frozen and maintained at this temperature Treponema pallidum and Treponema pertenue, upon thawing, exhibited normal morphology and motility and their virulence for rabbits was not appreciably altered after periods of at least 1 year. This applied to a number of different strains of each organism. The infectivity of material in which treponemes were scant was maintained as well as of material in which they were abundant. 3. At temperatures of -10 degrees C. and -20 degrees C. syphilis treponemes did not survive as long as 2 months. Death of the organism occurred not at the time of freezing but during the maintenance period. 4. Treponemes did not commonly survive freezing and desiccation, although one lot of dried material which contained T. pallidum was infective for rabbits 1 day after desiccation. 5. The viruses of human influenza, yellow fever, and spontaneous encephalomyelitis of mice when frozen and maintained at -78 degrees C. showed substantially the same titer after 6 months as before freezing. 6. Certain practical applications of the method are suggested.
Journal Article•10.1084/JEM.67.2.169•
Anaphylaxis in the isolated heart.

[...]

Herbert B. Wilcox1, E. Cowles Andrus1•
Johns Hopkins University1
01 Feb 1938-Journal of Experimental Medicine
TL;DR: The isolated hearts of guinea pigs sensitized to horse serum have been shown to react characteristically upon exposure to small amounts of antigen, and anaphylaxis in the isolated heart of the guinea pig is reported: a striking reduction in the rate of flow through the coronary vessels.
Abstract: The isolated hearts of guinea pigs sensitized to horse serum have been shown to react characteristically upon exposure to small amounts of antigen. The cardiac rate is temporarily accelerated and transient alterations in amplitude of contraction are to be observed. Electrocardiographic abnormalities, previously recorded by remote leads during anaphylactic shock in the intact animal, have been recorded by direct leads from the isolated perfused hearts of sensitized animals during this reaction. An additional effect of anaphylaxis in the isolated heart of the guinea pig is reported: a striking reduction in the rate of flow through the coronary vessels. The anaphylactic reaction of the isolated heart of the guinea pig has been compared with the action of histamine upon the same preparation and the effect of atropine upon each has been observed. The implications of certain quantitative differences in the influence of atropine upon these reactions are discussed.
Journal Article•10.1084/JEM.68.4.629•
The lymphatic pathway from the nose and pharynx : the absorption of dyes.

[...]

Joseph M. Yoffey1, Cecil K. Drinker1•
Harvard University1
30 Sep 1938-Journal of Experimental Medicine
TL;DR: Neither the dyes nor the Hydrokollag, though left in the nose for as long as 6 hours, were found to pass through the cribriform plate and reach the interior of the cranium.
Abstract: 1. In the monkey, dog, cat, and rabbit the cervical lymph duct was cannulated, and then a solution of T-1824, or trypan blue, or a fine graphite suspension, all in physiological saline, was dropped into the nose. T-1824 was used in all four animals, trypan blue in the cat and dog, the graphite suspension (Hydrokollag) in the cat alone. 2. No Hydrokollag was ever found in the cervical lymph. 3. Trypan blue and T-1824 appear in the cervical lymph 15 to 30 minutes after being placed in the nose of the cat and monkey, 51 to 53 minutes in the dog, and 14 minutes in the rabbit. 4. T-1824 and trypan blue were also absorbed from the nose directly into the blood. 5. Neither the dyes nor the Hydrokollag, though left in the nose for as long as 6 hours, were found to pass through the cribriform plate and reach the interior of the cranium. 6. In the monkey cervical lymph passes through a chain of five or more lymph nodes, in the rabbit frequently through two nodes, in the cat through one node except in rare instances, and in the dog through one node.
Journal Article•10.1084/JEM.68.2.161•
The effect of corticosterone and related compounds on the renal excretion of electrolytes

[...]

George W. Thorn1, Lewis L. Engel1, Harry Eisenberg1•
Johns Hopkins University1
31 Jul 1938-Journal of Experimental Medicine
TL;DR: In a suprarenalectomized dog desoxy-corticosterone acetate was substituted successfully for supraRenal cortical extract and the injection of a synthetic compound produced in normal dogs a very marked sodium and chloride retention and a potassium diuresis.
Abstract: The sodium and chloride retaining effect of suprarenal cortical extracts and of crystalline compounds derived from the suprarenal cortex parallels their effectiveness in maintaining suprarenalectomized dogs. All of the active compounds thus far studied produce a potassium diuresis when injected into normal dogs. The injection of a synthetic compound, desoxy-corticosterone acetate, produced in normal dogs a very marked sodium and chloride retention and a potassium diuresis. In a suprarenalectomized dog desoxy-corticosterone acetate was substituted successfully for suprarenal cortical extract.
Journal Article•10.1084/JEM.67.5.709•
On cross reactions of immune sera to azoproteins : ii. antigens with azocomponents containing two determinant groups

[...]

Karl Landsteiner1, J. van der Scheer1•
Rockefeller University1
30 Apr 1938-Journal of Experimental Medicine
TL;DR: The specificity of the antibodies was in general found to be influenced to some extent by the presence of a second group in the antigen and the relevancy of these observations for antibodies directed against natural antigens has been noted.
Abstract: Azoproteins have been prepared with azocomponents possessing two serologically active groups. On immunization with such antigens immune sera were obtained containing two separate, unrelated antibodies, each specific for one of the two groups and separable by absorption. In other cases one of the two structures was dominant, in that antibodies were formed only towards this and not towards the other grouping. The specificity of the antibodies was in general found to be influenced to some extent by the presence of a second group in the antigen. The relevancy of these observations for antibodies directed against natural antigens has been noted.
Journal Article•10.1084/JEM.68.2.191•
Production of experimental osteomyelitis in rabbits by intravenous injection of staphylococcus aureus.

[...]

R. H. S. Thompson1, René J. Dubos1•
Rockefeller University1
31 Jul 1938-Journal of Experimental Medicine
TL;DR: The results indicate that it is possible to produce consistently inflammation of the bones of rabbits by the mere intravenous injection of a suitable strain of staphylococcus, without resorting to any elaborate operative technique designed to localize the organisms in the bones.
Abstract: 1. The conditions under which a certain strain of staphylococcus (OH 172) causes in rabbits the development of bone inflammation have been described. 2. The virulence of the strain for rabbits was markedly raised by passage through this animal species, and especially after the culture had been recovered from a bone abscess. 3. The results indicate that it is possible to produce consistently inflammation of the bones of rabbits by the mere intravenous injection of a suitable strain of staphylococcus, without resorting to any elaborate operative technique designed to localize the organisms in the bones. It appears also that the inflammatory process so produced bears a close resemblance to staphylococcal osteomyelitis as occurring in human beings.
Journal Article•10.1084/JEM.67.5.739•
Serological evidence for the occurrence of infection with human influenza virus in swine

[...]

Richard E. Shope1•
Rockefeller University1
01 May 1938-Journal of Experimental Medicine
TL;DR: Antibodies capable of neutralizing human influenza virus were present in the sera of old swine on two New Jersey institution farms, but absent from theSera of young swine in the same farms, suggesting that the swine whose sera neutralized human flu virus had undergone an unrecognized human influenzairus infection acquired from man.
Abstract: Antibodies capable of neutralizing human influenza virus were present in the sera of old swine on two New Jersey institution farms, but absent from the sera of young swine on the same farms. The old animals had lived through the winter of 1936-37 in which outbreaks of upper respiratory tract disease were prevalent among the human inmates of the two institutions, while the young swine studied were born long after these outbreaks. It is believed that the swine whose sera neutralized human influenza virus had undergone an unrecognized human influenza virus infection acquired from man. The possible bearing of these observations upon the theory that swine influenza was originally of human origin is discussed.
...

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