bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Summary
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

Summary
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

Summary
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

Summary
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

Summary
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

Summary
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

Summary
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

Summary
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.
Relationship of the Anaphylaxis Sensitizing and Adjuvant Properties of Hemophilus Pertussis Vaccine
Authors: Kind Leon S. 
Published: January 2023

Summary
Pertussis vaccine administered along with chicken red blood cells (CRBC) in mice enhances the production of agglutinins to CRBC and also induces anaphylactic sensitivity to subsequent challenge doses of CRBC. However, the data presented indicate that serum agglutinins have little to do with mouse anaphylaxis. Pertussis vaccine stimulates the production of agglutinins to CRBC only if the CRBC are administered at the same time and via the same route as the pertussis vaccine. These conditions, however, are not necessary for the production of anaphylactic sensitivity.
Inactivation of Poliomyelitis Virus for the Preparation of Vaccines
Authors: Taylor A. R. , Kay W. W. , Timm E. A. , Hook A. E. , McLean I. W. 
Published: January 2023

Summary
An extensive series of experiments designed to establish the practicality of combining formaldehyde inactivation with ultraviolet irradiation as a method for the inactivation of poliomyelitis virus for the production of vaccines has been reviewed. The actual use of the combination method is illustrated by safety, stability and potency test data obtained in a series of experimental vaccines. These vaccines were also subjected to trial in humans. The objective has been to introduce and illustrate the feasibility of producing virus vaccines according to standards (11), particularly poliomyelitis, by the use of a combination of chemical (formaldehyde) and physical (ultraviolet) methods of inactivation.
Relationship of Virulence for Mice to Patient Source of Type 2 Polioviruses
Authors: Habel Karl , Silverberg Rosalie J. 
Published: January 2023

Summary
A total of 104 strains of Type 2 poliovirus, in first or second tissue culture passage, has been tested in mice. Eighty-eight produced paralysis by the intraspinal route; 15, with high titer intraspinally were positive by the intracerebral route. No correlation between tissue culture titer and mouse pathogenicity was apparent.
Comparison of clinical status of the patient source with tissue culture pathogenicity in monkey kidney epithelium showed an almost equal distribution of titers between patients with and without central nervous system (CNS) involvement. On the other hand, when the mouse intraspinal pathogenicity of the group of strains derived from patients without CNS involvement were examined in comparison to the results with the group from patients with CNS involvement there was a tendency for less virulence in the former group. This tendency for mouse CNS virulence to reflect virulence for human CNS was apparent only when the results for the entire 104 strains were considered since the whole spectrum of mouse virulence was represented by individual strains in both groups.
It is concluded that Type 2 poliovirus isolates obtained from human stools probably represent a mixture of mouse virulent and avirulent virus particles, both of which are pathogenic for monkey kidney epithelium in tissue culture and that the relative proportions of the two kinds of virus particles may be partially related to the type of clinical infection in the patient source.
Effects of Acute and Chronic Exposure to X-Radiation on Phagocytic Activity
Authors: Gyi Ko Ko , Marcus Stanley 
Published: January 2023

Summary
Exposure of mice to total body x-radiation in doses of either 300, 400 or 500 r does not affect the phagocytosis by reticuloendothelial cells of spleen of intravenously injected ThO2 when determined 2 days following radiation. However, similar investigations carried out on the seventh postradiation day indicated that 1) x-radiation in a dose of 300 r did not affect the localization of ThO2 in spleens; 2) a 400 r dose of x-radiation causes a transient depression of localization of ThO2 at 2 hr but 6 and 24 hr splenic uptake values were not different from the controls; and 3) x-radiation in a dose of 500 r significantly depressed the uptake by the mouse spleen of ThO2 at 2, 6 and 25 hr after injection. Whole-body x-radiation in a dose of 550 r suppressed the phagocytosis by reticuloendothelial cells of LAf1 mice when tested on the seventh postradiation day.
Chronic exposures of mice to x-radiation in doses of 25 r three times per week until accumulated doses reach as high as 825 r did not affect the phagocytic function of the reticuloendothelial cells.
Study of Microbic-Tissue Affinity by Perfusion Methods
Authors: Manwaring W. H. , Fritschen William 
Published: January 2023

Summary
The microbic-tissue affinity of an organ or group of tissues may be expressed as the average percentage of microörganisms deposited in these tissues per passage of a perfusion fluid. The microbic-tissue affinity varies with the organ or group of tissues tested. Thus, the central nervous system shows a microbic affinity of 0.5 per cent, the spleen a microbic affinity varying from 20 per cent to 60 per cent, and the liver a microbic affinity varying from 4 per cent to 80 per cent, depending upon the microörganisms tested. The remaining extra-hepatic tissues show affinities varying from 4 per cent to 6 per cent. The microbic-hepatic affinity is increased by immunization. The immune liver shows an affinity of at least 80 per cent for all microörganisms thus far tested. This increased hepatic affinity is due to the action of specific endothelial opsonins. The endothelial opsonins also increase the microbic-splenic affinity. So far as tested, however, they are inoperative with the other extra-hepatic tissues.
Hepatic Reactions in Anaphylaxis
Authors: Manwaring W. H. , Clark Wilfred S. , Chilcote Russell C. 
Published: January 2023

Summary
Marked fall in arterial blood pressure is produced by intravenous injections of peptone into dehepatized dogs. Canine peptone shock and canine anaphylactic shock therefore cannot be regarded as physiologically identical reactions. Recovery from peptone shock does not take place in dehepatized dogs.
Some Relations between Hydrogen Ion Concentration and the Antigenic Properties of Proteins
Authors: Falk I. S. , Caulfield M. F. 
Published: January 2023

Abstract
Introduction. One of the outstanding contributions of recent years to the study of the chemistry and physics of the proteins is the demonstration that the reactions of these substances with electrolytes are capable of stoichiometrical analysis. The work of Jacques Loeb and his collaborators, in this country, and of Sorenson and many others has gone far in removing some of these reactions from the fields of more empirical colloid chemistry into the realms of classical chemistry. They have indicated certain important possibilities in the quantitation of the dynamics of systems containing proteins. It is not possible, nor is it desirable, to review this work here. It is perhaps sufficient to refer to the original papers by Loeb and others in the Journal of General Physiology (1918, to date) and to the concise summary in the recent monograph by Loeb (1922) and to the review by Bancroft (1922).
Studies in Endothelial Permeability. I
Authors: Petersen W. F. , Levinson S. A. , Hughes T. P. 
Published: January 2023

Abstract
In the following series of papers we describe experiments that deal primarily with observations on endothelial permeability as studied by means of lymph analysis. The number of theoretical as well as practical therapeutic problems that are related in an intimate way to alterations of endothelial permeability may justify a study such as this even though we already possess a great amount of information gathered in the laboratories of Ludwig, Heidenhain, Asher, Carlson, Starling and others. Much of the older work was carried out at a time when the knowledge concerning the physico-chemical factors that might modify the permeability of the endothelium had not been developed, while more gross forces, as osmosis, were perhaps over-emphasized. The more recent communications have been quite numerous and in them cognizance has been taken of the modern concepts concerning cellular structure.
Studies on Endothelial Permeability. VI
Authors: Petersen W. F. , Jaffé R. H. , Levinson S. A. , Hughes T. P. 
Published: January 2023

Abstract
During the many years that tuberculin has been used in the therapy of tuberculosis, years in which it has had as enthusiastic approval as it has had unqualified condemnation by clinicians the world over, the basis of its use has centered about the idea that in some way tuberculin had value in increasing the “antibody resistance” to the infection or in desensitizing specifically against the toxic products of the infection. Just how this was induced has never been satisfactorily explained. Yet we do know definitely that if it has value in some cases, that value cannot be due to the antibody mechanism. Increase in antibody concentration in the blood need bear no relation whatever to either clinical improvement or regression.
Granted that therapeutic results may at times be observed, how are they brought about?
Human Hypersensitiveness to Different Proteins of Horse Serum
Authors: Hooker Sanford B. 
Published: January 2023

Summary
A triple reaction to horse serum has been shown to be due to specific hypersensitiveness, to serum albumin, euglobulin and pseudoglobulin. Thereby the evidence that these proteins are severally and specifically concerned with the manifestations of recurrent serum sickness is strengthened.