bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: Hirst George K. , Gotlieb Tamar 
Published: June 2004

Double infection of the allantoic sac with Melbourne and WSN viruses induced the formation of a combination virus, which had some of the antigenic properties of both parents and which maintained itself through serial passage in the chorioallantoic sac. In the course of prolonged passage in the egg, three varieties of combination virus were found. The first (X1) occurred in ten passages and was characterized as follows: X1 was produced in and could be successfully passed from those chick embryos that had received very large inocula of virus. The X1 hemagglutinin was efficiently inhibited by both M and W antisera. Each passage fluid, containing X1 as the predominant strain, also contained large amounts of the parent forms M and W. It is very likely that X1 reverted to parent types of virus at a high rate.
The second variety (X2) arose from the passage series of X1 and was carried for approximately 20 passages without definite alteration in its character. It differed from X1 in that it had the ability to appear as the predominant form occasionally in embryos that had received a limiting infective dilution of virus. Because of this, it seems probable that X2 reverted to parent types at a slower rate than X1. Like X1, this virus was never obtained in pure form and suspensions in which it predominated contained large amounts of M and W, especially the former. Good evidence was obtained that X2 reverted to M and W virus while multiplying in the chorioallantoic sac.
X3 was derived from passage of X2 virus after 32 transfers and can be characterized in several ways: (a) X3 yielded the only X3 fluids on passage in eggs. This was in striking contrast to X2 which could not be passed without giving rise to some fluids in which M and W predominated, (b) The X3 hemagglutinin was weakly inhibited by all but the highest concentrations of M serum, but was strongly inhibited by W serum. X2 was readily inhibited by relatively small amounts of both sera. (c) X3 virus, after several passages at limiting dilutions, was neutralized to a highly significant degree by specific M and W sera. This is not necessarily an essential difference from the behavior of X2 since technical difficulties (large amounts of M and W in X2 fluids) may have prevented the demonstration of equally striking double neutralization of this virus, (d) After five limiting dilution passages, the X3 virus retained the characteristics listed under (a) to (c). It is felt that the foregoing facts justify the conclusion that X3 is a stable virus which combines some of the specific antigens of two parent types.
EFFECT OF KETONE BODIES AND OTHER METABOLITES ON THE SURVIVAL AND MULTIPLICATION OF STAPHYLOCOCCI AND TUBERCLE BACILLI
Authors: Dubos René J. 
Published: June 2004

A study has been made of the fate of staphylococci and tubercle bacilli resuspended in aqueous media at slightly acid reactions. The tests were carried out at several acid reactions in balanced ionic media containing 0.5 per cent serum albumin. These experimental conditions were selected in order to approximate those which are probably encountered by pathogenic agents in inflammatory areas and in the intracellular environment of the leucocytes after phagocytosis.
The viability of the microorganisms at a given pH was markedly influenced by the composition of the medium, being decreased by addition to the latter of lactic, acetic, propionic, and butyric acids, and increased by the addition of certain ketone bodies such as dihydroxyacetone and pyruvic, ß-hydroxybutyric, α-ketoglutaric, and oxalacetic acids.
The presence of ketone bodies in the medium afforded to the microorganisms some protection against the bactericidal effect of lactic and acetic acids at acid reactions.
The minimum and the optimum pH for growth were found to be dependent on the composition of the medium. Both were higher in the presence of lactic, acetic, propionic, and butyric acids than in the media without organic acids added. In contrast, the addition of ketone bodies to the medium allowed microbial multiplication even in acid media (approximately at pH 5.3 or even lower).
The fact that lactic acid antagonizes, whereas ketone bodies favor, the survival and multiplication of staphylococci and tubercle bacilli at acid reactions, is discussed in relation to the high susceptibility to infection which is often associated with ketosis of various etiology.
INTRACELLULAR FORMS OF POX VIRUSES AS SHOWN BY THE ELECTRON MICROSCOPE (VACCINIA, ECTROMELIA, MOLLUSCUM CONTAGIOSUM)
Authors: Gaylord William H. , Melnick Joseph L. 
Published: June 2004

The intracellular development of three pox viruses has been studied with the electron microscope using thin sections of infected tissue.
Cells infected with vaccinia, ectromelia, and molluscum contagiosum viruses all form developmental bodies preliminary to the production of mature virus. Developmental bodies, believed to be virus precursors, are round to oval, slightly larger than mature virus particles, less dense to electrons, and have a more varied morphology.
It is suggested as a working hypothesis that the process of maturation of a virus particle takes place as follows. In the earliest form the developmental bodies appear as hollow spheres, imbedded in a very dense cytoplasmic mass constituting an inclusion body, or in a less dense matrix near the nucleus in cells without typical inclusion bodies. The spheres become filled with a homogeneous material of low electron density. A small, dense granule appears in each developmental body and grows in size at the expense of the low density material. Following growth of the granule, particles are found with the dimensions of mature virus and having complex internal structure resembling bars or dumbells. Mature virus is ovoid and very dense to electrons. An "empty" interior may be found within its thick walls.
EFFECT OF INFECTION WITH M. TUBERCULOSIS AND OF TUBERCULIN SHOCK ON THE SUCCINIC DEHYDROGENASE ACTIVITY OF GUINEA PIG TISSUES
Authors: Chaudhuri S. N. , Martin Samuel P. 
Published: June 2004

The kidney of guinea pigs infected with the H37Rv and BCG strains of M. tuberculosis showed a diminution in succinic dehydrogenase activity when measured by the tetrazolium technique. This effect was also seen in the liver and spleen of animals infected with the BCG strain. Sensitized animals showed similar results when given tuberculin in sublethal doses. The succinic oxidase was also low in the kidneys of animals infected with the H37Rv strain.
The depressed enzyme activity of the tissues of infected animals could be restored to normal by addition of normal tissue extract or dialysate. This suggests that the alteration in tissue metabolism observed in tuberculosis may depend upon the loss of some as yet unidentified factor important for succinic dehydrogenase activity.
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Horsfall Frank L. 
Published: June 2004

At a concentration of 0.0026 M, 2,5-dimethylbenzimidazole caused a number of alterations in the first cycle of multiplication of influenza B virus, Lee strain, in chorioallantoic membrane cultures in vitro. As determined by infectivity titrations in ovo on the membrane per se, the following alterations were observed: The duration of the latent period was increased by 80 per cent. The rate of increase in titer during the incremental period was somewhat decreased. The yield of virus was decreased by about 99 per cent.
When the compound was added to membrane cultures at various periods before or after inoculation with the virus, the following findings were obtained: On addition before or along with the virus, the substance caused about 99 per cent inhibition of multiplication. When added during the first 2 hours after inoculation, the compound caused inhibition of a degree which was inversely proportional to the time of addition. When added 3 to 8 hours after inoculation, the substance caused about 80 per cent inhibition. When added after the end of the latent period, no definite inhibition was obtained in the first cycle of multiplication.
These results are interpreted as indicating that 2,5-dimethylbenzimidazole acts by reducing the rate of biosynthetic mechanisms necessary for the reproduction of influenza virus particles.
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Horsfall Frank L. 
Published: June 2004

The activity of compounds which inhibit the multiplication of influenza virus can be measured in chorioallantoic membrane cultures in vitro by means of hemagglutination titrations on the medium. Studies on the reproducibility of virus reproduction in membrane cultures have revealed the major variables which affect the results and thus have led to the development of a precise technique. Under strictly controlled experimental conditions, the extent of reproduction of the virus in membrane cultures is predictable within narrow limits of variation.
With 105.5 EID50 of influenza B virus, Lee strain, and 5.75 cm.2 of chorioallantoic membrane per ml., the ratio of infective virus particles to susceptible allantoic cells appears to be approximately 1:28. Under these conditions, the evidence indicates that two cycles of multiplication occur and nearly maximal hemagglutination titers are found with culture medium at 36 hours. The extent of the deviation in the absolute titer in different experiments was only 0.112 log unit.
At a concentration of 0.0017 M, 2,5-dimethylbenzimidazole caused inhibition of the multiplication of influenza B virus, Lee strain, which persisted for at least 70 hours as measured by hemagglutination titrations on the culture medium. The degree of inhibition was closely comparable to that demonstrated by infectivity titrations on the membrane at the end of the first cycle of virus reproduction (1).
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Shunk Clifford H. , Heyl Dorothea , Horsfall Frank L. 
Published: June 2004

The degree of inhibition of multiplication of influenza B virus, Lee strain, in membrane cultures in vitro appears to be directly related to the concentration of the inhibitory compounds used in this investigation. With each of the alkyl derivatives of benzimidazole, evidence for such a relationship was obtained in the range between 60 and 90 per cent inhibition of virus multiplication.
Alteration of the structure of benzimidazole by substitution of alkyl radicals at various positions in either the benzene or the imidazole ring resulted in diverse differences in the capacity to inhibit influenza virus multiplication in vitro. Minor increases in inhibitory activity resulted when one to three methyl groups were introduced at certain positions in the molecule. Marked increases in inhibitory activity were achieved by more extensive substitution in either the benzene or the imidazole ring. The position and nature of substituent groups appeared to be of decisive importance.
Among the more highly active compounds were 2,4,5,6,7-pentamethyl-benzimidazole, 5,6-diethylbenzimidazole, and 2-ethyl-5-methylbenzimidazole. Further extension of the alkyl chain at position 2 caused no significant change in the inhibitory activity of the derivative. The most active compounds studied caused 75 per cent inhibition of Lee virus multiplication in membrane cultures in vitro at concentrations of approximately 0.0002 M. Some of the implications of these findings are discussed.
THE PERMEABILITY OF HUMAN SWEAT GLANDS TO A SERIES OF SULFONAMIDE COMPOUNDS
Authors: Thaysen Jørn Hess , Schwartz Irving L. 
Published: June 2004

A series of sulfonamide compounds, para-aminohippurate, and inulin were used to study the permeability of the epithelium of human sweat glands.
Inulin was not excreted in the sweat. The ratios of the concentrations in sweat to the concentrations in plasma, S/P, of sulfanilamide, sulfapyridine, sulfathiazole, sulfadiazine, and para-aminohippurate were found to be 0.69, 0.58, 0.13, 0.11, and 0.02 respectively, independent of the plasma concentrations and the sweating rates. The fact that the S/P ratios are thus unaffected by the absolute number of molecules transported suggests that these compounds enter into the sweat by simple diffusion and not via a specific secretory mechanism which could become saturated by increasing load. If this is so, the difference in the S/P ratios must be explained by an unequal permeability of the epithelium of the sweat gland to the various compounds and some explanation for these differences in the rate of excretion must exist in terms of physicochemical properties of the compounds.
A comparison between the S/P ratios and the pK values of the various sulfonamides indicates that the differences in their rates of excretion in the sweat depend upon the degree of ionization of the various compounds at the physiological pH. Compounds which are mainly non-ionized are excreted with high S/P ratios, whereas ionized compounds appear with low ratios. A quantitative relationship was shown to exist between the S/P ratio for each compound and the percentage of the compound which is non-ionized at pH 7.4.
THE RELATIONSHIP BETWEEN THE ACUTE PHASE RESPONSE AND ANTIBODY PRODUCTION IN THE RABBIT
Authors: Wood Harrison F. 
Published: June 2004

The ability of an adjuvant and its individual constituents to induce the production of Cx-reactive protein in rabbits has been studied. It was found that the adjuvant stimulated rabbits to produce large amounts of the acute phase protein for 3 to 6 days. Melted aquaphor blended with saline stimulated the production of Cx-reactive protein for 3 or 4 days. Mineral oil was less effective in stimulating the production of the protein than either adjuvant or aquaphor. Heat-killed Jamaica strain tubercle bacilli suspended in mineral oil did not induce the Cx-protein response.
The ability of subcutaneously administered adjuvant without antigen incorporated in the saline phase to potentiate the antibody response of rabbits to the intravenously administered antigens, C-reactive protein and human gamma globulin, was investigated. It was found that the adjuvant-treated animals produced more precipitating antibody to the two intravenously administered antigens than did the control animals given intravenous antigen alone.
SUSCEPTIBILITY OF MICE FREE OF THEILER'S VIRUS (TO STRAIN) TO INFECTION WITH TO VIRUS
Authors: Feltz Elmer T. , Mandel Benjamin , Racker Efraim 
Published: June 2004

A method for the establishment and maintenance of a colony of mice free of Theiler's (TO) virus has been described. This colony has been maintained since 1947 with but one instance of contamination in 1948.
Studies on the susceptibility of these mice to TO virus show that smaller doses are required to establish an infection of the intestinal tract than of the CNS.
A mutant strain of TO(B) virus has been isolated which, following oral administration to mice free of TO virus, is able to cause infection of the CNS with paralysis. When fed to stock mice that carry TO virus, this TO(B) strain does not cause paralysis or other signs of CNS infection.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B. 
Published: June 2004

The mortality rate for 80 Swiss weanlings infected with mouse hepatitis was 2.5 per cent in comparison with 98 per cent for 140 Princeton weanlings.
In Swiss weanlings discrete lesions, which generally failed to progress, were observed in the liver from the 3rd through the 10th day after intraperitoneal injection. The causal virus was demonstrable in peritoneal washings through the 21st day and less regularly in the liver through the 14th day. It was also detectable in both loci after subcutaneous injection.
Infant Swiss mice were susceptible through the 10th day of life, intraperitoneal injection being commonly followed by death.
The pathogenicity and titer of the virus were significantly increased by successive passage in Swiss weanlings.
The virus was detected in the blood of Swiss weanlings on subcutaneous injection only after it had been modified by passage.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: Nelson John B. 
Published: June 2004

The hepatitis of Princeton weanlings was not prevented by the prior injection of terramycin nor was the virus inactivated by exposure to room temperature.
Eperythrozoon coccoides was not demonstrable in blood films from Swiss and Princeton mice infected with the corresponding type of hepatitis virus.
Combined infection with this virus and eperythrozoa, originally obtained by Dr. R. B. McGhee from mice in association with Plasmodium berghei, was attended by the appearance of numerous organisms in the blood.
The development of eperythrozoa in dually infected Princeton mice had no effect on the outcome of the hepatitis.
In Swiss mice, animals with high natural resistance to hepatitis virus, the pathogenicity of this agent was markedly enhanced by combined infection with eperythrozoa.
Eperythrozoa were maintained throughout 18 successive passages in normal Princeton and Swiss weanlings with intact spleens.
The combined infection of Princeton mice with eperythrozoa and the virus component of Gledhill, Dick, and Andrewes, which is nearly inactive when injected alone, resulted in acute hepatitis with fatal outcome.
A STUDY OF ILLNESS IN A GROUP OF CLEVELAND FAMILIES
Authors: Jordan William S. , Gordon Irving , Dorrance William R. 
Published: June 2004

Feeding of stool supernates to volunteers has demonstrated that there are at least two different types—afebrile and febrile—of acute infectious non-bacterial gastroenteritis.
The afebrile illness, produced by the Marcy agent previously described, has an average incubation period of 60 hours and is characterized by watery diarrhea.
The agent (FS) responsible for the febrile illness has been carried through 3 human passages. The febrile disease has an average incubation period of 27 hours and is characterized by constitutional symptoms.
It is believed that the two agents are not the same because of the differences in incubation period, the clinical picture, and the absence of cross-immunity.
Intranasal instillation of throat washings obtained from 2 persons with gastroenteritis failed to produce illness in 2 groups of volunteers.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Bennett Ivan L. , Beeson Paul B. ,   With the Technical Assistance of Elizabeth Roberts
Published: June 2004

Injection of extracts or suspensions of various rabbit tissues was found to be without effect upon the body temperature of normal rabbits.
Occasionally, extracts of bone marrow produced transient fever, and saline extracts of acute inflammatory lesions of the Shwartzman and Arthus types were found to produce fever when injected intravenously.
Suspensions or extracts of polymorphonuclear leukocytes collected from sterile peritoneal exudates contain a heat-labile substance which produced fever whereas those of erythrocytes, macrophages, and lymphocytes failed to do so.
The cell-free supernatant fluid of sterile peritoneal exudates obtained at the stage when polymorphonuclear leukocytes predominate also proved capable of producing fever.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Bennett Ivan L. , Beeson Paul B. ,   With the Technical Assistance of Elizabeth Roberts
Published: June 2004

Further studies on fever production by injection of leukocyte extracts or cell-free supernatant fluids from peritoneal exudates in rabbits are reported.
Granulocytes collected from peripheral blood or from pleural exudates contain a heat-labile pyrogenic substance.
The material in extracts of leukocytes and in peritoneal fluids, which causes fever, is destroyed by heating for 30 minutes at 90°C. at pH 7.2 and at 70°C. at pH 4.5. It is active in producing fever over a pH range of 2.0 to 10.5 and maintains potency for as long as 6 months at 4°C.
The fever-producing substance in leukocyte extracts is not dialyzable. Its activity is not destroyed by trypsin, chymotrypsin, or ribonuclease. No evidence of plasma activator or inhibitor was detected.
Significant temperature elevation in the rabbit was effected by a quantity of leukocyte extract containing 0.76 mg. protein and 0.054 mg. polysaccharide.
The febrile response produced by the material under study was compared with that of Menkin's pyrexin as well as with that of bacterial pyrogens. Several significant differences were noted. The properties of pyrexin are similar to those of bacterial pyrogens.
Amidopyrine suppressed the febrile response to injection of leukocyte extracts, whereas neither amidopyrine nor cortisone influenced the appearance of pyrogenic material in induced peritoneal exudates.
Peritoneal fluids collected from rabbits made leukopenic by HN2 were found to contain a fever-promoting substance. Its character has yet to be determined.
It is concluded that there is present in polymorphonuclear leukocytes of rabbits a heat-labile factor capable of producing fever in rabbits and that the leukocyte is probably not the only source of such a factor.
STUDIES ON THE PATHOGENESIS OF KERNICTERUS
Authors: Vogel F. Stephen 
Published: June 2004

Kernicteric pigment was extracted by means of chloroform from the brains of 3 infants. Solutions of it gave a positive diazo reaction, and, as determined electrophotometrically, gave maximum absorption of light having a wavelength of 425 mµ, being identical in these properties with chloroform solutions of crystalline mesobilirubin.
Experimental kernicterus was regularly induced by injecting crystalline mesobilirubin intracerebrally in newborn kittens, the pigment staining the cerebral tissues a bright canary-yellow and being deposited abundantly in the nerve cells, as microscopic examinations showed, although these latter were otherwise intact. Bilirubin, likewise injected intracerebrally in newborn kittens, had no such effects.
The possibility is discussed that the blood-brain barrier is altered in some infants with hyperbilirubinemia in such a way that bilirubin crosses it and is then reduced within the brain to mesobilirubin thus giving rise to the cerebral pigmentation of kernicterus. The fact that the pigment itself does not seem to damage the neurons, as the present studies show, makes it necessary to seek some other cause for the neuronal damage that is sometimes seen, in association with the pigmentation, in the naturally occurring disease.
REGRESSION OF TRANSPLANTED LYMPHOMAS INDUCED IN VIVO BY MEANS OF NORMAL GUINEA PIG SERUM
Authors: Kidd John G. 
Published: June 2004

In the experiments here described transplanted lymphomas of two kinds regularly regressed following repeated injections of normal guinea pig serum intraperitoneally into mice carrying them, the animals meanwhile remaining lively and devoid of signs of illness or wasting. The lymphomas of untreated control mice, by contrast, usually grew progressively and killed their hosts within 20 to 30 days, and the same was true of the growth of other mice given repeated injections of horse serum or rabbit serum.
In similar experiments, the cells of a transplanted lymphosarcoma of rats were temporarily kept from proliferating by repeated intraperitoneal injections of guinea pig serum, though the cells of two transplanted mammary carcinomas of mice, and those of fibrosarcoma, grew unimpeded in hosts likewise treated.
Additional experiments related to the phenomenon here described, and a discussion of the findings as a whole, are given in an associated paper.