bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Immunization Against Plague
Authors: Chen T. H. , Meyer K. F.
Published: January 2023

A study of the diffusible antigens of P. pestis was undertaken, adapting a technique of double diffusion in gels first developed by Elek and by Ouchterlony. By testing combinations of P. pestis strains and fractions and P. pseudotuberculosis strains against anti-P. pestis gamma globulin, two antigen-antibody precipitation reactions common to both organisms were demonstrated, and the P. pestis-specific Fraction I and Fraction II (toxin) reaction zones were identified. The study confirmed previous laboratory findings that the avirulent but antigenic A1122 strain possesses a moderate amount of Fraction I, and the avirulent, nonantigenic 14 and TRU strains possess almost no Fraction I, and that strain 14 is toxic and strain TRU is essentially atoxic.

There was no indication of an antigen-antibody reaction specific for virulent P. pestis strains.

The method of double diffusion in gels appears to be a highly precise one for qualitative analysis of antigens and may be found useful for comparative studies of heterologous but closely related species and for studying the factors related to cross immunity.
Serologic Evidence of American Experience with Newborn Pneumonitis Virus (Type Sendai)
Authors: Jensen Keith E. , Minuse Elva , Ackermann W. Wilbur
Published: January 2023

The host range and growth characteristics of the Newborn Pneumonitis Virus (Type Sendai) have been studied. The hemagglutinin and serologic character have been examined and evidence is presented which supports the contention of the Japanese investigators that this is a hitherto undescribed virus.

Evidence has also been found that an antigenic stimulus exists in the American population which gives rise to antibodies which react with the Sendai agent. This antigenic entity is widespread geographically and has been present at least since 1936. At the present, antibodies occur with high frequency (40 per cent) and the highest levels are present in the age group under 18 years. Isolation of the agent in our population has not been successful and only in a few instances could a serologic diagnosis be made of infection.

The possible relation of the agent to the influenza group of viruses has been considered.
Use of Diphtheria Toxin and Toxoid in the Study of Immediate and Delayed Hypersensitivity in Man
Authors: Pappenheimer A. M.
Published: January 2023

Few areas in modern medicine remain so beclouded in mystery as the so-called allergic diseases. A substantial proportion of the human race each year suffers to a varying degree from asthma, hay fever, food allergies, drug allergies, contact dermatitis, and other unpleasant kinds of allergic manifestations. While there are few who would deny that hypersensitivity reactions, whether of the immediate or of the delayed inflammatory type, are triggered by a reaction in vivo between antigen and some form of antibody, we understand very little of how cellular damage is caused. It has been firmly established, in the case of the hay-fever type of allergy, that serum antibody is involved, and there is an increasing body of evidence which suggests that the type of antibody concerned (atopic reagin) possesses chemical as well as biological properties which distinguish it from the usual type of precipitating antibody studied by the immunologist in the laboratory.
The Effect of Whole Body X-Irradiation of Mice on Immunity to Tetanus Toxoid
Authors: Silverman Myron S. , Chin Paul H.
Published: January 2023

The inhibition by x-irradiation of the development of an immune response in mice by the injection of tetanus toxoid measured by the ability of the animals to survive 10 MLD of tetanus toxin has been found to depend on the x-irradiation dose and the time elapsing between the administration of the toxoid and exposure to x-irradiation. The higher the dose of x-irradiation, the greater was the amount of inhibition. Irradiation after injection of the antigen was found to be as effective in injuring the immune mechanisms as irradiation prior to the injection of antigen. Both the time interval between the administration of the antigen and exposure to irradiation during which injury occurred, and the time necessary for recovery of the antibody-forming mechanism were dependent upon the dose of x-irradiation. The higher the dose, the greater was the time interval, and the longer was the period of time necessary for recovery.
Absence of Neutralizing Antibodies Against Western Equine Encephalomyelitis in Sera of Children with Epilepsy
Authors: Bernet Carl P. , la Veck Gerald D. , Winn John F.
Published: January 2023

Sera from 28 epileptic children were tested in order to detect neutralizing antibodies against western equine encephalomyelitis (WEE). In only 1 was the serum found to be positive. Of 89 children used as controls, only 5 were found to have neutralizing antibodies against WEE. No association between WEE serum antibodies and idiopathic epilepsy was demonstrated.
Experimental Allergic Encephalomyelitis after the Excision of the Injection Site of Antigen-Adjuvant Emulsion
Authors: Freund Jules , Lipton Murray M.
Published: January 2023

It has been repeatedly shown that when certain antigenic material dissolved or suspended in physiological salt solution is injected into the subcutaneous tissue of animals, the surgical removal of the site of injection within a few minutes after injection does not prevent antibody formation (1). These observations are readily explained by the prompt dissemination of injected material. It was demonstrated by Cannon and Burt (2) that when Staphylococcus aureus or Serratia marcescens are injected into tissue of the ear of the rabbit, these microorganisms can be cultured from the blood, spleen, and liver even if the ear is amputated within a few minutes after injection. Furthermore, McMaster and Kidd (3) have shown that an intracutaneous injection introduces material very promptly into regional lymph nodes.

When antigens incorporated in water-in-paraffin oil emulsion with or without mycobacteria are injected into the tissues, the immune response is abundant and long sustained.
Organ Specificity of I131 Labeled Rabbit Kidney Eluates in Rats and Rabbits
Authors: Spar Irving L. , Bale William F. , Wolfe Dolores E. , Goodland Ruth L.
Published: January 2023

Rabbits were immunized against rat kidney. On the assumption that the kidneys of these rabbits would have bound antibodies against kidney tissue, the rabbit kidneys were removed, homogenized, washed, and extracted using mild heat (60°C) or acidity (pH 3.2). The eluted material was labeled with I131, further purified, and injected into rabbits and rats to test for preferential localization. Similar preparations were made using normal rabbit kidneys. Preparations from both sources showed preferential kidney localization in both rats and rabbits persisting for days. Localization was greater for preparations made from immunized kidney, but the difference has not been demonstrated to be statistically significant. One preparation of immunized kidney showed a concentration of I131 in the kidney of injected rabbits fifteen times higher than the next highest organ of thirteen organs studied, the spleen, in rabbits sacrificed three days and a week after injection. Three days following injection of another type of labeled preparation into rabbits, 10% of the injected I131 was found localized in the kidneys.

Heat eluted and purified labeled eluates of kidneys from the immunized rabbits, but not normal rabbits, localized in rat small intestine as well as kidney following intravenous injection. It proved possible largely to separate the rat intestine localizing component from the kidney localizing component of these preparations.

Preparations made in a similar manner using the heat elution techniques from rabbit spleen, striated muscle, adrenal, and lung showed little kidney localizing tendency when injected into rabbits and rats.
Neuropathic Effect of Newcastle Disease Virus in Mice and Modification of Host Response by Receptor Destroying Enzyme, Viral Interference, and Xerosin
Authors: Groupé Vincent , Dougherty Robert M.
Published: January 2023

The toxic effects of certain viruses have been modified by viral interference, prior injection of receptor destroying enzyme (RDE), heat inactivated RDE, or xerosin. Similarly, the neuropathic effect of egg-propagated Newcastle disease virus (NDV) for mice was also modified by these agents. One strain, Cal-NDV, which was neuropathic for mice only in low dilution was found to interfere in mice with the neuropathic effect of another strain, RO-NDV, which was neuropathic for mice in high dilution (10-5).

Prior intracerebral injection of influenza B virus or RDE modified host response to both concentrated and dilute NDV. However, xerosin modified only the neuropathic effect of Cal-NDV and of concentrated RO-NDV, but failed to delay paralysis or death following inoculation of dilute RO-NDV.

It is suggested that further study of the neuropathic effect of NDV for mice may lead to a better understanding of the possible relationships between viral toxicity, masked virus, and incomplete virus.
Antistaphylocoagulase in Experimental Staphylococcal Infections
Authors: Boake W. C.
Published: January 2023

A study has been made of the effects of anti-staphylocoagulase in acute staphylococcal infections of rabbits and mice. Rabbits actively immunized with coagulase were more resistant to intravenous challenge with coagulase-positive, but not coagulase-negative staphylococci. When mice were injected intraperitoneally with coagulase-positive staphylococci suspended in a clotting system (fibrinogen/co-factor), serum from rabbits immunized with coagulase diminished the virulence of these staphylococci provided it was allowed to come into contact with the challenge organisms for 30 minutes before the addition of the clotting system. The virulence of the organisms was also diminished under the same conditions by human serum containing coagulase-inhibiting antibodies. This diminution of virulence was not produced by alpha antitoxin or staphylococcal agglutinating serum, and was not demonstrable against coagulase-negative staphylococci. It is considered that the diminution of virulence observed in mice was due to the in vitro inhibition of coagulase activity, and that the active immunity observed in rabbits was probably associated with in vivo inhibition of coagulase activity.
Escherichia Coli 0127:B8, a Serotype Causing Infantile Diarrhea
Authors: Stulberg Cyril S. , Zuelzer Wolf W. , Page Robert H.
Published: January 2023

By means of a hemagglutination procedure, the antibody response of premature infants with diarrhea in an epidemic caused by Escherichia coli 0127:B8 was studied. In preliminary experiments with two adult volunteers who had ingested large numbers of these microorganisms, the specificity of the hemagglutinating-antibody was established by the patterns of antibody response and by absorption tests. Hemagglutinating-antibodies were detected in normal adults and transplacental transfer of such antibody was demonstrated. In infected newborn infants, the antibody response was distinguished from transplacental antibody by its pattern of development.
Virus Adsorption and Plaque Formation in Monolayer Cultures of Trypsin-Dispersed Monkey Kidney
Authors: Youngner J. S.
Published: January 2023

Virus adsorption and plaque formation by poliomyelitis, herpes-B, and vaccinia viruses have been studied in monolayer cultures of monkey kidney. Under the conditions employed, it was found that the time required for adsorption of 50% of the plaque-forming units was approximately 30 minutes for herpes-B virus and between 1 and 2 hours for poliomyelitis and vaccinia viruses.

The fate of virus not adsorbed at the time of agar overlay was also investigated. The results suggest that unadsorbed particles of poliomyelitis virus diffuse through the agar, eventually reach the cell layer and produce plaques. Unadsorbed particles of herpes-B or vaccinia viruses seem to diffuse poorly, if at all, and do not produce plaques if dispersed in the agar overlay. It has been suggested that this difference in “diffusion-adsorption” pattern may be a function of the size of the virus particles involved.

Adsorption rates were (a) directly related to the temperature of incubation, (b) not demonstrably affected when pH of the diluent was varied from 6.0 to 8.0 and were (c) the same for large and small numbers of virus particles in the inoculum.
Response of Ferrets to Mumps Virus
Authors: Gordon Irving , Pavri Khorshed , Cohen Sophia M.
Published: January 2023

Ferrets inoculated intranasally with large doses of infectious egg-adapted mumps virus developed bronchiolitis and pneumonitis resembling that caused by some influenza virus strains. This was followed by the appearance of specific antibodies in high titer. The immunologic response evoked by noninfectious virus by this route and by subcutaneous inoculation of either infectious or noninfectious virus was relatively low. Mumps virus was recovered from nasal washings, lungs, or turbinates several days after inoculation, but proof of propagation of the virus in the ferret respiratory tissues was not obtained. The data provide additional analogies between mumps virus and the other members of the Myxovirus group.
The Serology of Newcastle Virus Infection
Authors: Bang F. B. , Foard M.
Published: January 2023

Neutralization of Newcastle virus by 3 different types of antisera (chicken, rabbit, and human) was studied in several ways.

When embryos were inoculated with the mixture of virus and serum on the chorio-allantoic membrane, there was a direct, roughly 1:1 relationship between the amount of virus neutralized and the dilution of serum used. When the mixtures were inoculated into the allantoic sac, the loss of neutralizing activity by the diluted sera exceeded the amount of dilution, i.e., the slope was 2 or more. These results were obtained with all 3 sera. The steeper slope obtained with allantoic inoculation in the case of chicken and rabbit sera seemed to depend on a greater neutralization following allantoic inoculation with undiluted serum. This difference in effective neutralization brought about by different routes of inoculation was not apparent with diluted sera. Incubation of serum and virus for periods up to 2 hr at 35°C had no effect on the amount of virus neutralized by convalescent chicken sera but did increase the neutralization brought about by immune human sera. Incubation of serum and virus before adding red cells increased the amount of inhibition of red cell agglutination caused by all 3 types of sera. Chicken antisera delayed the death of embryos beyond the 6-day period during which embryos inoculated even with minimal infectious doses do not survive. This delay in virus effect was not produced by rabbit or human sera.
Studies on the Relationship of Potassium to Influenza Virus Multiplication
Authors: Levine Alvin S. , Bond Phyllis H. , Scala A. R. , Eaton Monroe D.
Published: January 2023

Potassium deficiency was found to suppress in tissue culture: Growth of chorioallantoic epithelium and fibroblasts.Multiplication of the PR8 strain of influenza virus.Respiration of normal or virus-infected tissue by about 10%.

Addition of K+ reversed these suppressive effects.

The results indicate that K+ deficiency affects host-virus interactions in 2 ways: Accessibility of virus attached to tissue to neutralization by immune serum.Intracellular synthesis of new virus.

Inhibition of viral multiplication by α-amino-p-methoxyphenylmethanesulfonic acid was reversed by excess K+. Hypotheses for the relationship of viral synthesis to K+ metabolism are discussed.
Studies on Organ Specificity
Authors: Witebsky Ernest , Rose Noel R.
Published: January 2023

Crude saline extracts of rabbit thyroids proved to be antigenic for rabbits. The technique of immunization consisted of the intradermal injection of 0.05 ml of a mixture of tissue extract plus Freund adjuvants into each of the 4 footpads in the rabbit. The percentage of rabbits showing circulating antibodies varied from experiment to experiment. Rabbit thyroid antibodies were demonstrated by complement fixation and precipitation techniques. In addition, erythrocytes tanned according to Boyden's procedure and coated with thyroid extracts provided a sensitive tool for the demonstration of rabbit thyroid antibodies in high antiserum dilution. The thyroid antibodies are tissue-specific rather than group-specific, reacting with the thyroid extracts of any rabbit tested regardless of whether the rabbit itself produced thyroid antibodies or failed to do so. Thyroidectomized, or partially thyroidectomized, rabbits injected with extracts of their own thyroid glands produced antibodies reacting with their own thyroid extracts as well as with thyroid extracts of any other rabbit tested.
Use of Vinyl Plastic Containers in Tissue Cultures for Virus Assays
Authors: Rightsel W. A. , Schultz P. , Muething D. , McLean I. W.
Published: January 2023

A simple, rapid, and inexpensive method for the performance of virus and drug assays in tissue culture systems has been described using a molded vinyl plastic panel containing a series of depressions. The plate is available commercially and, when sterilized with alcohol, is devoid of toxicity to trypsin-dispersed monkey kidney cells and HeLa cells. The multi-purpose plastic container is inexpensive, requires little preliminary processing so that it may be rapidly prepared for use, and then is autoclaved and discarded at the termination of tests.
Immunological Cross-Reactions Studies by the Ouchterlony Gel Diffusion Technique
Authors: Korngold Leonhard
Published: January 2023

A theoretical discussion of the precipitin patterns obtained with cross-reacting systems, as studied by the Ouchterlony gel diffusion technique, is presented. The conditions that result in single or double spurs are described, and experimental examples are given.
The Relationship Between the Dose of Taiwan Cobra (Naja Atra) and Taiwan Habu (Trimeresurus Mucrosquamatus) Venom and Time of Death in Mice
Authors: Lin Chau-Ching
Published: January 2023

The relationships between dosage of Naja atra venom and of Trimeresurus mucrosquamatus venom and the death-times of mice have been examined from experiments using intravenous injection. The observations were found to be well represented by the equation.

The parameters of the dose-death time equation for both Naja atra and Trimeresurus mucrosquamatus were different from those found by Christensen and Finney (9) for Naja flava in mice. The weight of mice can be disregarded when weighing between 15 to 21 g for Naja atra and 15 to 20 g for Trimeresurus mucrosquamatus.
Serum Agar Measuring Aid (Sama)
Authors: Glenn W. G.
Published: January 2023

The Serum Agar Measuring Aid (SAMA) is an accessory device for the Photronreflectometer. The combination permits photometric quantitation of serum agar column reactions.

Results and evaluation indicated that accurate measurement of the density and diffusion of zones of precipitation can be made by beginning laboratory technicians. SAMA can also be used to quantitatively determine antibody response, follow protein fractionation, and identify unknown participants in precipitin reactions.
Purification of Kidney Components Capable of Neutralizing Kidney Localizing Anti-Rat Kidney Antibodies
Authors: Yagi Yasuo , Korngold Leonhard , Pressman David
Published: January 2023

A soluble material capable of inhibiting the localization of kidney localizing anti-kidney antibodies was isolated from a trypsin digest of rat kidney. Further digestion with ribonuclease and desoxyribonuclease removed all phosphorus and nucleic acid components, leaving material whose specific activity was 25 to 50 times that of the original trypsin digest and which contained protein and some carbohydrate.

The material can neutralize only about 75% of the kidney localizing antibodies. Therefore, there must be localizing anti-kidney antibodies present in the anti-RK sera which are directed against other antigens than those studied here.
The J Substance of Cattle
Authors: Stone W. H.
Published: January 2023

Studies of the titers of naturally occurring anti-J sera in two groups of cows, one consisting of 8 and the other of 23 animals, have shown that the concentration of anti-J varies considerably among individuals and for the same individual from one time to another. The rise and fall of anti-J levels among the first group of individuals studied during a 28-month period and among the second group studied during a 19-month period was correlated with the season of the year. In both groups of animals, the highest titers were found during the late summer and early autumn (August to October), and the lowest titers were found during the late autumn and winter (December to March). The physiologic basis for this striking seasonal variation is unknown at present.
Studies on Newcastle Disease Virus (Miyadera Strain)
Authors: Tokuda Masao
Published: January 2023

Newcastle disease virus (Miyadera strain) can be successfully transmitted to suckling mice by the intracerebral route. Although the incubation period of Newcastle disease in mice is longest in the 1st mouse passage generation and becomes shorter with additional passage, the LD50 of virus in mice is highest when egg-adapted Newcastle disease virus is inoculated and lowest in the 1st mouse passage generation, and then it becomes higher again and constant. After passage in mice, infectivity of the virus for the chick becomes weaker; but immunization with this live virus protects chicks from infection with egg-adapted Newcastle disease virus, and their sera are positive in the hemagglutination-inhibition test and indirect complement-fixation test with egg-adapted Newcastle disease virus. The hemagglutinins from mice infected with Newcastle disease virus are demonstrated at pH 6.1, and their activities are inhibited not only by hyperimmune sera against mouse-adapted Newcastle disease virus but also by sera against the egg-adapted virus. For preparation of hyperimmune serum for use in the complement-fixation test, it is best that guinea pigs be immunized intracerebrally with allantoic fluids infected with the Newcastle disease virus. The allantoic membranes of the embryos are best suited as complement-fixing antigen. Newcastle disease virus can be transmitted in brains of guinea pigs through only a few passages. Cats also develop cerebral symptoms when they are inoculated with the virus intracerebrally.
The Effect of Cobalt-60 Gamma Radiation on Tetanus Antitoxin Formation in Mice
Authors: Hale William M. , Stoner Richard D.
Published: January 2023

Cobalt-60 γ whole body irradiation markedly depresses tetanus antitoxin in mice when given 6 hr, 1 day, 7 days, 14 days, and 21 days before a primary injection of fluid tetanus toxoid. The animals irradiated 14 and 21 days before the primary stimulus recovered sufficiently from radiation to react to the primary injection, since they later produced considerable amounts of antitoxin when given a secondary antigenic stimulus. The inhibitory effect of 650 rep γ radiation on the primary antibody response was as effective when alum precipitated toxoid was used for the primary stimulus. A radiation dose of 350 rep given 1 hr before the secondary stimulus had little effect on depressing antitoxin formation. γ Radiation doses of 450 to 750 rep effectively inhibited the secondary antitoxin response. The depressing effect was more marked with increased amounts of radiation. γ Radiation of 650 rep severely inhibited the secondary antitoxin response when radiation was given 6 hr to 30 min before the secondary antigenic stimulus. A total dose of 1,000 rep given in 4 doses of 250 rep at 5-day intervals depressed the secondary response by only 40%. When 650 rep whole body radiation was given in a single exposure the depressing effect on antitoxin formation was much greater than when the radiation was given in 10, 5, 3, or 2 divided doses. When radiation exposure was given at the peak of the antitoxin level (10th day after the secondary stimulus) and the mice were bled 10 days later, the antitoxin level was slightly reduced. There was no appreciable effect on the antitoxin level when mice were given 650 rep 21 days after the secondary stimulus and bled 5 days later. If the radiation was given 21 days after the second injection and the animals were bled 10 and 21 days later, the depressing effect was more pronounced than when radiation was given 10 days after the second injection. The depressing effect on the antitoxin level was greater when serum was obtained 21 days after exposure to radiation than on the 10th day post-radiation.
The Nature of the Formalin Inactivation of Poliomyelitis Virus
Authors: Timm E. A. , McLean I. W. , Kupsky C. H. , Hook A. E.
Published: January 2023

Studies of the formalin inactivation of poliomyelitis virus have shown that the reaction, under the conditions studied, does not follow first order rate laws. Inactivation rate curves plotted in accordance with the first order rate laws show that during the first few hours of the reaction there is a disproportionately great drop in infectious titer which appears on the curve as a sharp deviation from the theoretical straight line. This pattern of the reaction was apparent under varying conditions of pH, temperature, and formalin concentration. Similarly, the pattern was not affected by varying concentrations of protein and amino acids in the virus-suspending media or by subjecting virus suspensions to varying clarification procedures. Tests also indicated that the pattern of the reaction was not an artifact resulting from technical errors in sampling. The rate of the reaction varied with formalin concentration, temperature, pH, and amino acid and protein concentration of the suspending media. Practical implications of the results are presented in the discussion.
Systemic and Local Anaphylaxis in the Albino Rat
Authors: Lipton Murray M. , Stone Sanford H. , Freund Jules
Published: January 2023

Summary and Conclusions

Lethal anaphylactic shock has been elicited in rats sensitized with bovine serum albumin combined with adjuvants. Of 10 rats sensitized with bovine serum albumin combined with paraffin oil adjuvants containing mycobacteria, 6 died after intravenous injection of the antigen. Of 9 rats sensitized with bovine serum albumin combined with adjuvants without mycobacteria, 1 died after intravenous injection of the antigen. Skin reactions were elicited in rats sensitized with bovine serum albumin or egg albumin in paraffin oil emulsions. The reactions in animals receiving tubercle bacilli in the emulsion were more extensive and of longer duration than in rats sensitized without mycobacteria. The histologic changes in the sites of intense skin reactions were similar to those in the Arthus reaction in the rabbit. Rats immunized with bovine serum albumin with adjuvant emulsions produced relatively large amounts of precipitating antibody. The high incidence of anaphylactic death and the intense skin reactions in rats so immunized are probably referable to the high antibody titers. Relatively large amounts of antigen used in skin tests frequently did not elicit skin reactions in sensitized rats; the injection of more dilute antigen solutions caused reactions. When several skin tests were made simultaneously, a high dose at one site inhibited the reactions at the sites of injection of lower doses of antigen. In rats similarly sensitized, tests made with only the lower dosages showed intense skin reactions. This may be due to desensitization caused by antigen entering the general circulation and combining with the available antibodies.
Concerning the Mechanism of Complement Action
Authors: Becker Elmer L.
Published: January 2023

Summary and Conclusions

Cells containing the 1st, 2nd, and 4th components (EA C′1,4,2) of guinea pig complement are capable of hydrolyzing p-toluene sulfonyl l arginine methyl ester (TAMe). Unsensitized cells treated with complement, or sensitized cells not so treated, do not have this capability. The action of EA C′1,4,2 on TAMe was shown to have the characteristics of an enzyme reaction. A quantitative correlation between changes in the C′1 and TAMe esterase activity of EA C′1,4,2 has been found, whether the changes have been caused by variations in source and concentration of hemolysin, source of sheep red cells, amount of C′1 used to form the cells, incubation with different diisopropyl fluophosphate concentrations, or incubation with various concentrations of ethylene diamine tetra acetic acid. TAMe has been shown to protect the C′1 activity on sensitized cells against inhibition by diisopropyl fluophosphate.

It is concluded that C′1 is a TAMe esterase. It is further suggested that C′1 is another example of a protease with TAMe esterase activity.
Intracellular Localization of Tobacco Mosaic Virus in Mouse Liver
Authors: Erickson John O. , Hensley Thomas J. , Fields Max , Libby Raymond L.
Published: January 2023

Localization of intravenously injected radioactive TMV in mouse liver has been studied by cellular fractionation and electron microscopy.

TMV uptake by the mitochondria as measured by radioactivity has been confirmed by electron microscopy of the isolated fractions.

No evidence was obtained for the localization of TMV in the nuclei of any cell types.

Electron microscopy of thin sections revealed aggregates of TMV only within vacuoles of Kupffer cells. Failure to detect TMV in sections of mitochondria is explained in terms of lack of sensitivity of the method.
Aspects of the Immune Hemolytic Reaction
Authors: Plescia O. J. , Amiraian K. , Heidelberger M.
Published: January 2023

The composition of C′ was altered in three independent ways: 1) by heating serum at 56°C for a few minutes, 2) indirectly by varying the degree of sensitization of erythrocytes, and 3) by adding to whole C′ reagents used for component titrations. In each case differences in concentration dependence were evident, as shown by changes in the shapes of the curves and the concentration of cells at which the extent of hemolysis tended to become constant. The composition of C′ seems to play an important part in determining the nature of the dependence of the extent of hemolysis on the concentration of erythrocytes.
In Vitro Bactericidal Activity of Blood for Pasteurella Tularensis
Authors: Stanziale William G.
Published: January 2023

Conclusion and Summary

The bactericidal activity of various species of mammalian whole blood for P. tularensis was determined under controlled conditions, and was found to vary among the species tested. The whole blood of the cow, dog, and sheep were found to exhibit a significant amount of bactericidal activity resulting in a decrease of 1 log in the number of bacteria inoculated; the whole blood of the other species tested showed much smaller amounts of activity. The bactericidal activity of dog blood was equally effective against concentrations of bacteria ranging from 101 to 107 organisms per ml of final test mixture.

The bactericidal activity of the species tested correlated to some degree with the resistance of these animals to experimental infections with P. tularensis.

The bactericidal complex in the blood in the case of the dog resides in the plasma fraction. The experimental results do not suggest that the complex resides in the cells and diffuses into the plasma, where its effect is demonstrated.
Studies on the Chemotherapy of Viral Infections
Authors: Liu Oscar C. , Carter Joseph E. , Malsberger Richard G. , DeSanctis Armand N. , Hampil Bettylee
Published: January 2023

The effect of caprochlorone on influenza virus infection in mice has been studied. The titers of virus in the lungs of the treated mice were on the average 10-fold lower than that found in the lungs of the control group. The efficacy of such treatment, however, decreased when the infectious dose was greater than 10 MLD50.

The possibility of a combined therapy using both caprochlorone and antiserum was investigated. Human γ globulin was used as the source of antiserum. A definite synergistic effect was demonstrated with the combined therapy in that mice infected with 3000 MLD50 were saved, whereas infections with 3 and 30 MLD50 were prevented by caprochlorone alone and γ globulin alone, respectively. It has been shown also that mice infected with the virus 3 days previously were cured by the combined therapy. The significance of this is discussed.
Observations on a Qualitative Difference Between the Antibody of Primary and Secondary Response
Authors: Foster W. D.
Published: January 2023

The antibodies, produced in rabbits against human erythrocytes, of the primary and secondary response have been studied with reference to the possibility of their being qualitatively different. In agglutinating activity no difference was detected and no “incomplete” agglutinin was demonstrated. However, primary and secondary response antibody appeared to differ in their hemolytic activity in that primary response sera were more weakly hemolytic with rabbit complement and with low concentrations of guinea pig complement than were secondary response sera, even when the hemagglutinin content was comparable.
The Preparation and Properties of Purified Anti-Hapten Antibody
Authors: Karush Fred , Marks Robert
Published: January 2023

A general procedure has been developed for the specific purification of anti-hapten antibody. It takes advantage of the low solubility of fibrinogen and involves the precipitation of the antibody with azofibrinogen. The antibody is separated from the antigen at neutral pH by addition of a weakly bound hapten, and is freed of the hapten by repeated precipitation with a mixture of dibasic and monobasic potassium phosphates. This method has been applied to the purification of antibody specific for the optically isomeric forms of the haptenic group, phenyl(p-azobenzoylamino)acetate. The yield of purified antibody is in the neighborhood of 50% of that initially precipitated from the antiserum. Some properties of the purified antibody preparations are described. The superiority of this method over those previously published by other authors lies mainly in the maintenance of a constant neutral pH (7.4) throughout the procedure.
The Measurement of the Response of Immunized Mice to Infection with Mycobacterium Tuberculosis Var. Hominis
Authors: Youmans Guy P. , Youmans Anne S.
Published: January 2023

Data have been presented which show the response of normal and vaccinated mice, in terms of time of death, to intravenously administered increasing doses of virulent human-type tubercle bacilli strain H37Rv. The deaths of normal mice infected intravenously with small doses and the deaths of vaccinated mice infected intravenously with slightly larger doses were found to be so anormally distributed that neither the mean survival time nor the median survival time could be used as the measurement of the average response. Instead, the response of such mice to the tuberculous infection was measured by recording the number of mice which survived 30 days or longer, and the rationale for this procedure is given.

Only by a determination of the relationship between the number of tubercle bacilli in the challenge dose and the response of both normal and vaccinated mice can a suitable single challenge test dose of virulent tubercle bacilli be selected to measure the degree of immunity to this disease in mice. Using this method of evaluation, it was shown that neither large single doses nor small single challenge doses of the H37Ra strain of Mycobacterium tuberculosis var. hominis could be used to measure the immune state of mice, since both normal and vaccinated mice responded to such doses in a similar fashion. Only when intermediate doses (0.5 to 1.5 mg) were used was an adequate differentiation between normal and vaccinated mice obtained.

Alternatively, the degree of immunity in mice may be measured by determining the 30-day lethal dose/50 (30-DLD50). This can be done by determining the number of tubercle bacilli which will kill 50% of the normal mice within 30 days, and comparing this with the number of tubercle bacilli required to kill 50% of the vaccinated animals within the same period.

Application of the above principles to the problem of the measurement of the immunity produced in mice by the injection of various agents has shown that vaccination with 3 strains of BCG produced a significantly greater degree of immunity in mice than did vaccinaton with a fourth strain of BCG or with the H37Ra strain. The latter 2 strains were equivalent in their immunity-producing ability. Ultraviolet irradiation almost completely abolished the ability of tubercle bacilli to stimulate production of immunity in mice, whereas heat (126°C for 20 min) reduced the immunizing capacity of the H37Ra and BCG strains about 50%. Unrelated organisms such as Bacillus subtilis, Bacillus sphaericus, and Hemophilus pertussis did not stimulate the production of any immunity in “Strong A” strain mice.

Booster doses of the H37Ra strain administered either 2 or 4 days before challenge nearly doubled the immune response of “Strong A” mice to tuberculous infection.

The “Strong A” strain mice were found to develop a higher degree of acquired immunity to tuberculous infection than mice of the “Rockland” all-purpose strain.
Studies on the Cytotoxic Effect of Newcastle Disease Virus (NDV) on Ehrlich Ascites Tumor Cells
Authors: Prince Alfred M. , Ginsberg Harold S.
Published: January 2023

The findings of Moore and co-workers (1, 2) were confirmed in that Ehrlich ascites tumor cells recovered the capacity to propagate in mice when suspensions of NDV and tumor cells were held at 21–23°C for 4 hr in vitro. It was demonstrated that “recovery” of Ehrlich ascites tumor cells from the action of NDV occurred only when conditions existed which permitted elution of virus from tumor cells. At 37°C, recovery was prevented by the establishment of a stable union between virus and tumor cell. The union involved loss of the ability of virus-cell complexes to combine with specific viral antibody. This loss took place within 10 min after the virus cell mixture was brought to 37°C. These data suggested that the killing of tumor cells by NDV did not occur solely as a result of the reaction of virus with the tumor cell surface.
The Cross Reactions of Antisera Prepared Against Four Human Cell Strains in Continuous Tissue Culture
Authors: Goldstein Milton N.
Published: January 2023

Four human cell strains of normal and malignant origin were used for the production of antibodies in rabbits. These antisera, when tested for cytotoxicity, showed species specificity but no tissue specificity in tissue culture test systems. Antisera prepared from any one of the 4 human strains produced cytotoxic changes in all the other strains as well as in recently explanted human cells of normal and malignant origin. Absorption of an antiserum with cells of normal or malignant origin completely removed all cytotoxicity.
Multiple Antibody Responses Following Immunization of Human Subjects with Diphtheria Toxoid
Authors: Kuhns W. J. , Dukstein W.
Published: January 2023

Precipitation reactions were carried out in a fluid and semi-solid medium utilizing human immune antitoxic sera unabsorbed and absorbed with P-proteins. These methods indicated that 11 of 59 Schick negative subjects hyperimmunized with diphtheria toxoid subsequently formed anti-diphtherial antibodies in addition to antitoxin. The average antitoxin titer was higher in sera showing evidence of multiple antibodies than in sera showing no evidence of multiple antibodies. The quantitative precipitation reactions of 6 of the 11 antitoxic sera were studied using preparations of crude and purified diphtheria toxin. Four immune sera exhibited quantitative characteristics of multiple antigen-antibody systems prior to absorption with P-proteins. Absorption of the sera with P-proteins caused a removal of considerable antibody nitrogen relative to antitoxin nitrogen as judged by altered quantitative behavior of absorbed sera in the presence of purified toxin. The average unit antitoxin nitrogen values before and after absorption of sera with P-proteins were as follows: unabsorbed sera 1.7 μg N/unit, absorbed sera 1.9 μg N/unit. The average in vivo/in vitro ratio was 1.02 before absorption and 1.03 following absorption.
Mechanism of Antibody Formation
Authors: Koshland Marian Elliott
Published: January 2023

Summary and Conclusions

Highly purified diphtheria toxin was trace-labeled with radioactive iodine without measurable loss of its immunological specificity. A detoxified preparation of the labeled material adsorbed to aluminum phosphate gel was inoculated subcutaneously into the footpad of previously immunized guinea pigs. The distributionand catabolism of the antigen at the site of inoculation in the popliteal node and in the blood were determined as a function of time. Control experiments with labeled NaI, di-iodotyrosine and guinea pig albumin were performed in a similar manner.

It was found that a reservoir of both the toxoid and the homologous albumin was localized at the site of injection. From there small amounts of protein were continually released to pass through the draining lymph gland and eventually enter the circulation. This pathway was shown to be the main means of protein transport from the skin to the blood.

The determinations of antigen-bound radioactivity indicated that the largest per cent destruction of toxoid occurred at the primary locus of antibody formation, the popliteal node. Appreciable catabolism of antigen was also observed in the injection area and in the circulation. In comparison the homologous albumin was not significantly degraded in the skin and lymph tissues, although in the blood it was destroyed at the same rate as antigen, presumably through the normal process of enzymatic breakdown. Since the rates of elimination of albumin and residual toxoid were identical in the tissues examined, it would appear that neither the alum nor local antibodies exerted a specific retention effect on the antigen.

When these data were correlated with quantitative measurements of the antibody concentrations in the same tissues, the extent of antigen catabolism in the subcutaneous alum granuloma was shown to be dependent on the available antibody. In the lymph and blood tissues a fraction of the antigen either resisted degradation or was degraded very slowly despite the presence of a large excess of free antitoxin. No direct relationship could be demonstrated between the amount of antigen present in the lymph node and the amount of antibody synthesized. The significance of these results in elucidating the role of the reinjected antigen in both the primary and secondary stimulation of antibody formation is discussed.
Studies on the Cytotoxic Effect of Newcastle Disease Virus (NDV) on Ehrlich Ascites Tumor Cells
Authors: Prince Alfred M. , Ginsberg Harold S.
Published: January 2023

It has been confirmed that the reaction of NDV with Ehrlich ascites tumor cells resulted in ultimate death of infected cells. This interaction was not accompanied by demonstrable multiplication of infectious, hemagglutinating, or complement fixing particles. Prior to death, cells grew at an accelerated rate for a minimum of 4 hr. The initial growth rate depended on the number of infecting particles, i. e., a very large number of viral particles per tumor cell produced no increase in growth rate, whereas an increased degree of stimulation was caused by smaller numbers of particles per cell. Hyperplasia was followed by disappearance of cells from the peritoneal cavity in a manner suggesting lysis. The cytotoxic effect was shown to result from the action of the viral particle—the activity followed the virus during adsorption and elution from red blood cells, and during ultracentrifugation. Prior treatment of cells with RDE or with specific anti-NDV immune serum protected against viral damage. Immune serum injected only 15 min after viral inoculation did not prevent death of tumor cells. Cell injury could be prevented by prior treatment of cells with ultraviolet inactivated NDV without concomitant reduction in the power of such cells to combine with infectious NDV. The injurious activity of NDV was readily destroyed by ultraviolet light. However, the cytotoxic property of the virus was not as sensitive to ultraviolet irradiation as was the infectious property of the agent.
The Purification of Formol Diphtheria Toxoid by Multi-Membrane Electro-Decantation
Authors: Largier John F.
Published: January 2023

Formol diphtheria toxoid was purified by a combination of multi-membrane electro-decantation, ammonium sulphate fractionation and acid precipitation, yielding a product with a potency of 2950 Lf/mg protein nitrogen without impairing the antigenieity in guinea-pigs.

Physieochemical investigation showed that the purified toxoid was homogeneous by gel diffusion, electrophoresis, diffusion and sedimentation measurements. Using sedimentation and diffusion data a molecular weight of 73,300 and a frictional ratio of 1.34 were calculated.

The iso-electric point of formol diphtheria toxoid, as determined by a new method using a modified form of M.M.E.D. apparatus, was found to be pH 4.15 and pH 4.25 in acetate buffers of ionic strengths 0.05 and 0.025 respectively.
Antibody Synthesis by Homotransplanted Cells and Tissues
Authors: Stavitsky Abram B.
Published: January 2023

By attention to methods for preparing the donor and recipient animals and to transplantation techniques large amounts of diphtheria antitoxin and anti-bovine γ globulin were produced in virtually every experiment. It was concluded that under these conditions antibody synthesis was identical with the process in the donor. The major sites of antibody production were the popliteal and mesenteric lymph nodes, spleen and bone marrow, whereas the lung, liver and kidney were inactive. It was postulated that the cellular entity concerned with antibody production is transferred from mother to daughter cells during mitosis. By pretreatment of the lymph nodes with sheep blood the period between booster injection and transfer with antibody production was reduced from 3 days to 1 hr. By using tissue fragments rather than cells for transplantation this interval could be reduced from 3 days to 1 day. Addition of antigen to lymph node cells from primarily stimulated animals caused antibody production only when these cells were transplanted without the washing off of antigen. On the other hand, addition of antigen to splenic cells from such donors resulted in antibody formation even when the cells were washed before transplantation. Possible explanations for these observations have been discussed.
The Effect of Complements on Soluble Antigen-Antibody Complexes
Authors: Weigle William O. , Maurer Paul H.
Published: January 2023

The ability of complement from various animal species to precipitate soluble rabbit antigen-antibody complexes in the region of antigen excess has been demonstrated. Guinea pig and rabbit complements precipitated the soluble complexes better than human or pig complements, and guinea pig complement precipitated the complexes better than rabbit complement. The failure of pig and human complements to precipitate soluble complexes to the same extent as guinea pig and rabbit complements may be partially caused by several factors: (1) an inhibition resulting from cross reactions between the antibodies in the complexes and the human and porcine proteins, (2) the presence of an inhibitory factor which was found to be inactivated upon aging the serum, and (3), the physical and chemical characteristics of complement molecules themselves. Two possible hypotheses were set forth to describe the mechanism involved in the precipitation of soluble complexes by complement. These hypotheses were: (1) complement fixed to the complexes to such an extent that the increase in weight and/or neutralization of charges caused the complexes to precipitate, and (2), the complement was multivalent to antibody and/or antigen and, therefore, was able to link the complexes together to form precipitating aggregates. The ability of guinea pig and human complement to cause precipitation of “univalent” (co-precipitating) antigen-antibody complexes was demonstrated.