bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Influenza Complement Fixation Antigens Derived from Allantoic Fluids and Membranes
Authors: Kirber Maria Wiener , Henle Werner
Published: January 2023

A comparison was made of virus (V) and soluble (S) antigens derived from allantoic fluid and membrane of chick embryos infected with influenza A or B viruses.

The antigens derived from membranes proved indistinguishable from the corresponding fractions prepared from allantoic fluid, as measured by serum cross-absorption and by complement fixing activity in the presence of convalescent and post-vaccination sera.

Depending on the concentration of the inoculum, optimal titers of V and S antigens in the membranes were obtained in 24 to 48 hours, whereas they reached their highest titer in the fluid in 48 to 72 hours. The optimal sources for V were allantoic fluids harvested after 48 hours, whereas S was best prepared from membranes collected after incubation periods of 48 hours or less. The data presented indicate that complement-fixation tests with V from allantoic fluid and S from allantoic membrane represent reliable diagnostic tools.
A Comparison of Physicochemical Measurements of Hyaluronidase and of Neutralizing Antibodies Thereto
Authors: Harris T. N. , Harris Susanna
Published: January 2023

The depolymerization of hyaluronic acid by bacterial and testicular hyaluronidase has been studied in relation to the question of whether the same or different enzymes are involved in the three physicochemical reactions by which this depolymerization can be measured: mucin-clot-prevention, turbidimetry and viscosimetry.

Twenty-seven preparations of hyaluronidase of a wide variety of sources and wide range of potency were examined by the three methods, and the respective measurements of enzyme activity for each preparation were found to be in fairly close proportion. Preparations of bacterial and testicular hyaluronidase were tested at intervals during exposure to heating and ultraviolet irradiation, and the progressive loss of potency of the enzyme was found to proceed at similar rates by all three methods of measurement. Similar results were obtained during partial specific absorption of the enzyme by increasing amounts of antiserum.

The antihyaluronidase titers of rabbits subjected to a short course of injections of streptococcal and of testicular hyaluronidase were measured by the three reactions, and were found to rise and fall concomitantly in all three tests.

The evidence presented here is consistent with the concept that the three physicochemical methods by which hyaluronidase can be detected measure the same depolymerase of hyaluronic acid.
Specificity of Radioiodinated (I131) Immune Globulin As Determined by Quantitative Precipitin Reaction
Authors: Masouredis S. P. , Melcher L. R. , Koblick D. C.
Published: January 2023

The reaction between human serum albumin and I131 trace iodinated rabbit antibody was studied by the quantitative precipitin reaction. The amount of radioactivity found in each immune precipitate was proportional to the antibody nitrogen precipitated. Under the iodinating conditions described (1.3 iodine atoms per antibody molecule) no loss of immunologic specificity of rabbit antibody labelled with I131 was demonstrated.
The Production of Potent Anti-Human Globulin (Coombs Reagent) in Rabbits Immunized with Serum Adjuvant Mixtures
Authors: Emerson Charles P. , Franklin William , Lowell Francis C.
Published: January 2023

Certain hemolytic disorders are characterized by the attachment of a globulin to the erythrocyte membrane, this globulin possessing the characteristics of an antibody for antigenic determinants associated with the surface of the red cells (1). Cells with attached globulin, i.e., sensitized cells, may agglutinate spontaneously when placed in serum, albumin solutions, or other protein-containing mediums, but usually do not agglutinate when suspended in saline. Erythrocytes, so sensitized, are encountered in the blood of some patients with idiopathic acquired hemolytic anemia and erythroblastosis fetalis (2–4). Similar sensitization may follow exposure of normal red cells in vitro to nonagglutinating antibody, occasionally present in the serum of those “iso-immunized” by pregnancy or transfusion (5–7). The adherent globulin may be demonstrated most readily by the so-called “Coombs test,” the basis of which is the agglutination of these cells by an antiserum prepared in rabbits injected with human serum.
Mouse Encephalomyelitis
Authors: Dean Donald J.
Published: January 2023

The establishment and maintenance of a colony of mice free from mouse encephalomyelitis virus are described. Non-infected mice at all ages and by whatever route tested are more susceptible than latently infected animals to infection with the homologous strain. They are also more susceptible to heterologous strains of mouse encephalomyelitis virus. The infectivity of mouse encephalomyelitis is influenced by maternal passive immunity, by acquired humoral immunity, and by the resistance that develops with age. Inhibition of mouse encephalomyelitis virus by the feces of infected mice is confirmed.
Factors Involved in Haemagglutination by the GDVII Strain of Murine Encephalomyelitis Virus
Authors: Fastier Lyle B.
Published: January 2023

During the purification of GDVII virus from infected mouse brains by red cell adsorption and elution it was found that haemagglutination with human red cells occurred at both 4 C and at room temperature. This reaction had previously been reported to take place only at the former temperature and the present work demonstrated that different rates of adsorption of virus on erythrocytes existed for the purified virus and the crude saline suspensions of infected mouse brain. These observations are discussed as a possible explanation of the mechanism of non-specific inhibition of GDVII virus haemagglutination by normal mouse brain extracts described elsewhere.

An investigation of the mechanism of haemagglutination by the GDVII virus disclosed that in a salt-free medium adsorption of haemagglutinins was complete at 4 C and partial at 18 C. Once virus-red cell combination had taken place elution occurred only into an electrolyte-containing solution. While the haemagglutinin titre was not materially influenced by the presence of different electrolytes at a static molarity, a study of the adsorption and elution rates revealed considerable variation among the salts tested. Of particular interest was the observation that elution of adsorbed virus was considerably retarded by calcium ions. These findings have been compared and contrasted with corresponding reactions exhibited by members of the influenza group of viruses.
The Influence of Acth and Cortisone on Histamine and Anaphylactic Shock in the Guinea Pig
Authors: Malkiel Saul
Published: January 2023

Adrenocorticotrophic hormone and cortisone are without any apparent effect on the end results of histamine shock, or of passive or active anaphylaxis in guinea pigs.

Since this paper was presented for publication a report appeared by Dworetsky, Code and Higgins [Effect of cortisone and ACTH on eosinophils and anaphylactic shock in guinea pigs, Proc. Soc. Exper. Biol. & Med. 75: 201–206, (1950)] which substantiates these findings.
The Adsorptive Behavior of Bacteriophage T2 with Certain Inorganic Materials
Authors: Shepard Charles C. , Woodend William G.
Published: January 2023

The adsorptive behavior of T2 bacteriophage to several inorganic adsorbents has been investigated. Displacement was found to be a prominent feature and the bacteriophage could be displaced from columns of aluminum oxide in a predictable manner with meat infusion broth, or with a preparation of bovine serum albumin. The salt concentration was also important; when the sodium chloride was less than 10−2 to 10−3 M, adsorption was markedly decreased, whereas at 10−1 M or above adsorption was marked. Decreased adsorption was also seen at pH values above 8 with some adsorbents.
Agglutinating Antibodies in Serum and Feces
Authors: Barksdale W. L. , Ghoda Akira
Published: January 2023

Fecal extracts and sera from a number of cases of Flexner and Sonne types of dysentery have been tested with so-called phase antigens from wild type Shigella paradysenteriae W, Shigella sonnei and certain of their serologically “non-specific” mutants. Serum and fecal extracts were found to differ in the titer and in the specificity of their agglutinins. This, coupled with the fact that they appear at different times during the course of disease, suggests that they are synthesized in different parts of the body.

We are indebted to Dr. Koibong Li and S/Sgt. D. J. Yackanich for technical assistance throughout these studies.
Attempts at a Quantitative Estimation of the Second Component of Complement
Authors: Heidelberger Michael , Jonsen Jon , Waksman Byron H. , Manski Wladyslaw
Published: January 2023

Reagents without detectable second component have been prepared from human, guinea pig and pig complements. The hemolytic power of mixtures of these reagents with human, guinea pig and pig complements has been studied quantitatively. Hemolysis with a given reagent is indicated to be an undetermined function of its content of third component.

Values found for second component in several human complements lie within limits previously established by qualitative titrations and, in general, do not differ more than by ±15 per cent from the mean. Variations in the case of guinea pig complement were greater.

Discrepancies between values obtained with different reagents may be due to a partially masked anticomplementary property of a given complement-reagent combination or to incomplete mutual equivalence of components of complement from different species.
The Interaction of Influenza Virus and Intact Human Erythrocytes Observed by Replica Technique in the Electron Microscope
Authors: Rhian Morris , Evans Alfred S. , Melnick Joseph L.
Published: January 2023

Influenza virus particles on the surface of intact human erythrocytes were observed in the electron microscope by means of replica technique. It was found that a solution containing 0.10 M phosphate buffer with added dextrose or serum albumin to make the solution isotonic was more satisfactory for suspending the cells and virus, than was sodium chloride (0.03 to 0.17 M). Following treatment of cells with virus three changes in the surface of the cells were observed: (1), presence of individual virus particles on the surface; (2), localized eroded or pitted areas which may contain single or clumped virus particles; and (3), a general roughening of the cellular surface. Single cells may show all three types of change.
The Electron Microscopy of Chick Embryo Membranes Infected with Newcastle Disease
Authors: Kilham Lawrence , Morgan Councilman , Wyckoff Ralph W. G.
Published: January 2023

Sections of chorioallantoic and amniotic membranes infected with Newcastle-disease virus show spheres and rods on the surface of the epithelial cells when examined by the electron microscope. These particles are morphologically similar to the elementary bodies seen in ultracentrifuged preparations of virus from infected egg fluids. Changes in infected cells include thickening of the superficial membrane followed by vacuolation and increased density of the cytoplasm.
Concurrent Infection with Influenza A and B Viruses in a Single Epidemic of Influenza
Authors: Kilbourne Edwin D. , Anderson Harold C. , Horsfall Frank L.
Published: January 2023

Investigation of an influenza epidemic in a children's institution disclosed concurrent infection of the population with both influenza A virus and influenza B virus. Individuals of the population were found to have been infected with influenza A virus, with influenza B virus, or with both viruses. The availability of pre-epidemic sera from the entire population made it possible to determine the actual incidence of inapparent infection during an influenza outbreak; clinically inapparent infections occurred in 8% of the population. Collateral studies with hamsters established that a mammalian host may be simultaneously infected with influenza A and B viruses and develop antibodies against both viruses, although the degree of antibody response may be less than that resulting from infection with either virus alone.
Protease Activation in Immune Reactions
Authors: Geiger Walton B.
Published: January 2023

The biochemical events that immediately follow reinjection of antigen into sensitized animals and lead to anaphylactic symptoms or tissue reactions have not been fully elucidated. Among the intermediate steps that have been suggested are the liberation of toxic substances such as “anaphylotoxin” (1), histamine (2, 3, 4), or acetylcholine (5, 6), and activation of enzymes such as proteases (7–15).

Theories that antigen-antibody reactions are followed by the activation of proteases have received some experimental support. In 1915 Bronfenbrenner (7) added egg albumin to sera of rabbits that had been sensitized to this protein nine days earlier, and observed that dialyzable nitrogenous material was liberated. He attributed this result to auto-digestion of the serum by “digesting ferments” liberated under these conditions. Analogous results were obtained with other antigens. Jobling, Eggstein and Petersen (8) reported similar experiments and conclusions at about the same time.
Studies on Conglutinin
Authors: Flick John A. , Villafañe Aida L.
Published: January 2023

The results obtained in this study show that when two separate immunological systems are combined, mixed agglutination is obtained in relatively high concentrations of the sera but homologous aggregation alone results with sufficient dilution. Where mixed agglutination occurs, it is due largely or entirely to nonspecific serum factors acting on the sensitized red cells. These non-specific factors are of the nature of conglutinin, or are identical with conglutinin. The possibility that antibody per se under certain conditions in the system studied may also produce the mixed agglutination effect has not been eliminated.

Whole normal human serum, its various fractions, or gum acacia, all of which showed conglutinating activity, increased the percentage of mixed agglutination when added in adequate concentrations to the system.

These findings suggest that, in essence, both the Bordet and the lattice theories are substantially applicable to the mechanism of agglutination, the lattice theory best explaining the specific union of antibody with antigen to bring about aggregation, and the Bordet theory offering a reasonable basis for many side effects involving non-specific constituents of serum.
Paradoxical Effect of Congo Red on the Toxicity of Streptolysin S for Mice
Authors: Rosendal Kirsten , Bernheimer Alan W.
Published: January 2023

The effect of congo red on the lethal action of streptolysin S has been investigated. The toxicity of mixtures containing congo red and a lethal dose of streptolysin S was found to be a function of the amount of dye used. When the amount was small (of the order of 1 μg), the mixtures possessed little or no toxicity; when large (100 μg), but far below the toxic dose of congo red alone, the mixtures invariably proved toxic. An hypothesis attempting to resolve the paradoxical observations is suggested.

No protection was afforded mice by pre-treatment with congo red regardless of whether a small or a large dose was used. Binding of the dye by serum accounts for the failure of streptolysin S to be inhibited in vivo. A simple method of estimating the capacity of serum components to bind congo red is described.
The Susceptibility of Irradiated Mice to Infection as a Function of Post-Irradiation Time
Authors: Shechmeister I. L. , Bond V. P. , Swift M. N.
Published: January 2023

The susceptibility of mice to airborne Streptococcus zooepidemicus was determined over a 50-day period following 350 r whole body X-irradiation. Bacterial LD50 values were determined for normal and irradiated mice on 12 different post-irradiation days during this period, and the changes in susceptibility in each case expressed as the ratio of the two. The resulting curve relating susceptibility to post-irradiation time indicated a linear increase in susceptibility over the first 15 days, reaching a peak five times that of controls, followed by an exponential drop approaching the control level shortly after 30 days.

The possible relationship of this phenomenon to other radiation effects is discussed. Mice subjected to sublethal doses of radiation exhibit a time pattern of change in susceptibility to infection which is different from the time pattern reported for various post-irradiation changes.

Previous immunological studies following irradiation have not been sufficiently quantitative to permit interpretations or correlations with the results herein reported.
Studies in Specific Hypersensitiveness
Authors: Cooke Robert A.
Published: January 2023

The quantitative relations in partial desensitization are contrasted with those that obtain in the state of lessened sensitiveness in allergy, the differences being such as to indicate a difference in the mechanism of these two phenomena. The phenomenon of “local exhaustion” of the allergic cutaneous reaction described by Mackenzie and Baldwin is studied and found, in disagreement with these authors, to be non-specific. It is proposed to distinguish the lessened sensitiveness induced in allergy from the state of desensitization in anaphylaxis by designating the former condition as a state of hyposensitization.
Bronchial Asthma and Allied Conditions
Authors: Larsen Nils P. , Paddock Royce , Alexander H. L.
Published: January 2023

An asthma clinic was established in the out-patient department of Bellevue Hospital, New York City, in October, 1919. For the year 1919–1920, the scope of the work included a detailed study of the clinical aspects of asthma, which was published (1). During the year 1920–1921 the following investigations were attempted, the results of which are embraced in this paper: (a) A continued study of the clinical considerations of asthma, (b) observations on skin reactions, (c) effects of vaccine therapy.

During the year, 105 cases of bronchial asthma were studied in detail; 25 of pollen sensitization; 2 of urticaria, and 2 of angioneurotic edema.

Clinical Observations From a practical standpoint, it is important that cases of bronchial asthma be recognized clinically as speedily as possible, since special methods for diagnosis and relief of the condition are attempted. The urgency of the presenting symptom, however, leads to quick transfer to the asthma clinic, when the dyspnea is supposedly asthmatic.
Studies with Influenza Virus B of Recent Human Origin
Authors: Ledinko Nada
Published: January 2023

Genetic interaction was demonstrated between a mouse-unadapted influenza B virus, Rob, of recent human origin, which produces extensive pulmonary consolidation and multiplication of virus only upon initial inoculation into the mouse lung, and the Mil strain of influenza B virus. Interaction was also found to occur between Mil and mouse-adapted Rob viruses. An analysis of the distribution of mouse lung virulence among the progeny has indicated that multiple genetic factors are involved in both “crosses.” Back-recombination to give the original strains was obtained with “recombinants” isolated from the experiment involving Mil and unadapted Rob viruses.

The results indicate that the initial effects of pulmonary consolidation and multiplication in the mouse lung by an unadapted influenza B virus may be controlled by genetic mechanisms.
The Antigenic Composition of the Various Anatomic Structures of the Canine Kidney
Authors: Goodman Morris , Greenspon Seymour A. , Krakower Cecil A.
Published: January 2023

Previous studies from this laboratory (1) have shown that within the frame of reference of the isolated glomerulus, the “nephrotoxic” antigen(s), the heterologous serum to which can produce glomerulonephritis in the donor species, is localized within the basement membrane of the glomerular capillaries. The parietal capsule and the cellular elements of the glomerulus could be excluded as sites of this antigen(s). In the course of these investigations additional methods were evolved whereby tubular epithelial cells from the cortex of the kidney and tubular basement membrane could be obtained in relatively pure form. Heterologous serums developed against these two additional renal components failed to produce glomerulonephritis in the donor species. The present investigation was, therefore, designed to determine and contrast the antigenic composition of all the isolated principal renal structures on an in vitro basis.
Poliomyelitis Antibodies in Human Gamma Globulin
Authors: Opton Edward M. , Nagaki Daizo , Melnick Joseph L.
Published: January 2023

Sixty-five samples of human gamma globulin representative of the materials used for poliomyelitis prophylaxis in the United States during the summer and fall of 1953 and 1954, and two samples of Japanese origin, were assayed for poliomyelitis neutralizing antibodies by means of tissue culture neutralization tests. Using a fixed challenge of 100 tissue culture doses of virus and varying dilutions of gamma globulin the average titers for antibodies against virus types 1, 2, and 3 were 1:1130, 1:1060, and 1:770, using data provided by both cytopathogenic and colorimetric tests.

Gamma globulin preparations derived from human placentas had as much poliomyelitis neutralizing antibody as the best preparations made from pooled plasma.

Comparison of untreated human plasma pools and the gamma globulins derived from them demonstrated that poliomyelitis antibodies were concentrated in this fraction. However a sample of beta globulin and a sample of gamma globulin, both manufactured from the same pool of human plasma, showed neutralizing antibody levels of the same order of magnitude.
A Study of an Unusual Hemagglutinin in a Pooled Human Serum
Authors: Makinodan Takashi , Macris Nicholas T.
Published: January 2023

“Routine” antibody screening test of the D-1 serum showed the presence of only the “incomplete” Rho antibody.

Trypsin-treated O rh cells agglutinated very strongly in this serum.

The “T-agglutinin” was not present in this serum.

The agglutination tests before and after absorption of the serum with untreated and enzyme-treated Rh-positive and Rh-negative cells show that the agglutination of the trypsinized red blood cells in this serum is due to an agglutinating factor independent of the Rho antibody.

This factor was found to be equally reactive at 0°C, 22°C, and at 37°C for 30 minutes, and absorbable, nondialyzable and thermolabile at 65°C for one hour, unlike the reversible agglutinin factor.
In Vivo Uptake of Isotope-Tagged Tuberculin by Leukocytes
Authors: Ritts Roy E. , Favour Cutting B.
Published: January 2023

PPD has been tagged with I131 without altering its biological potency. The fate of I131-tagged PPD given intravenously to normal rabbits has been followed by measuring radioactivity found in plasma and on the leukocytes and erythrocytes of these animals during the subsequent 24 hours. I131-tagged PPD is partially cleared from the plasma during the first 24 hours after injection. It is firmly absorbed to the leukocytes during the first 4 hours after injection. No tag is found on leukocytes after 4 hours. The significance of leukocyte uptake of a tagged bacterial protein is discussed.
In Vitro Production of Diphtheria Antitoxin by Tissues of Immunized Animals
Authors: Stavitsky Abram B.
Published: January 2023

Lymph node and spleen fragments and slices from immunized animals appeared to produce diphtheria antitoxin when placed in a suitable medium. Disruption of the tissues or inclusion in the medium of various inhibitors of oxidative metabolism such as cyanide or dinitrophenol resulted in complete inhibition of antibody production. Moreover, the in vitro process of antibody formation appeared to parallel both the in vivo process and the passive transfer reaction whereby antitoxin appeared in the blood of normal rabbits following the injection of lymph node or splenic cells from immunized animals. In fact, the striking parallels between the in vitro and passive transfer reactions suggested that these two reactions might be fundamentally similar.

It appears that under the conditions employed the tissue fragments and slices continued in vitro the net synthesis of antitoxin initiated in vivo.
Susceptibility of the Pigeon (Columba Livia) to Infection with Western Equine Encephalomyelitis Virus
Authors: Kaplan William , Winn John F. , Palmer Dan F.
Published: January 2023

Subcutaneous inoculation of pigeons with 160 chick LD50 and 1600 chick LD50 of WEE virus produced early viremias which persisted for at least 96 hours. Virus was recovered from 3 out of 15 pigeons inoculated with lesser amounts of virus, but in these cases virus was slower in appearance and is considered due to contact infection through handling. WEE infection, also apparently through contact, occurred in 1 of the 5 pigeons in the group which received no virus artificially.
Poliomyelitis and Other Antibody Patterns in Natives of Tahiti and Raiatea
Authors: Horstmann Dorothy M. , Kraft Lisbeth M. , Melnick Sarah , Mascola Anne
Published: January 2023

In 1951, the island of Tahiti experienced its first recorded epidemic of poliomyelitis. An unusual feature of the outbreak was the age distribution of cases, the majority being in the 10-to 24-year age group, with relative sparing of young children. The present study is concerned with attempts to designate the type of virus responsible for the epidemic, and to determine if serological tests could shed any light on the problem of the age distribution of cases.

The evidence obtained by virus isolation, and by results of neutralizing and CF antibody studies of convalescent cases, points to a type 1 epidemic. The patterns of neutralizing and CF antibodies in normal individuals suggest that the population had not been exposed to this type of virus for a number of years, that a high proportion of those under 20 to 29 were infected during the outbreak, but the infection reached clinical levels chiefly in older children and young adults. Those over 30 were spared presumably because of previous infection, and the possession of low level neutralizing antibodies.

The presence of neutralizing antibodies to all three types of poliomyelitis viruses in all age groups indicates that these agents have been prevalent on the islands in the past, although no epidemic had been recorded previously.
Quantitative Studies on the Bactericidal Actions of Serum and Complement
Authors: Muschel Louis H. , Treffers Henry P.
Published: January 2023

The bactericidal reaction, as studied with a new photometric growth assay, has been shown to parallel the hemolytic reaction in a number of respects: a stimulation by, if not an absolute requirement for, Mg ion and antibody-complement relations which can be expressed by identical equations. In a typical experiment 700–860 molecules of antibody and 1.5 × 107 molecules of complement were necessary to kill one organism, Salmonella typhosa, at the 50% end point. This amount of antibody is calculated to cover 0.03–0.7% of the bacterial cell surface. Heating at 56°C for a few minutes has been shown to decrease the bactericidal activity, particularly of weak sera, by partial destruction of antibody. Rabbit serum has an activating effect on guinea pig complement, human serum a depressing effect in the bactericidal although not in the hemolytic reaction. The relative titer of two sera is shown to vary with heating, and the species of complement used. Additional observations are presented on the Neisser-Wechsberg inhibition, and the mechanism of the bactericidal effect.
Fractions of Pig Complement
Authors: Leon Myron A. , Plescia Otto J. , Heidelberger Michael
Published: January 2023

An inhibitor of g.p. C′ activity has been found in two fractions isolated from pig serum. For extents of hemolysis ranging from 0.2 to 0.8 the inhibitor reacts with one or more components of g.p. C′ according to first order kinetics with respect to C′i, the inhibited components of C′, if the assumptions are valid. The reaction is accelerated by an increase in temperature from 25°C to 37°C, as well as by a decrease in the concentration of divalent cations. The inhibitor, like C′1, is heat labile and is fixed by immune precipitates formed with rabbit antibody but not by those formed with horse antibody. This suggests that the inhibitor is partially degraded or denatured C′1 which forms hemolytically inactive complexes with one or more components of g.p. C′.
Studies on Antigenicity of Inactivated Influenza Virus
Authors: Fong Jacob
Published: January 2023

The level of neutralizing antibodies in the serum of mice was highest after immunization with live virus. No significant difference in antigenicity was noted for mustard-inactivated and formalin-inactivated vaccines. Virus inactivated with 5 × 10-4 M mustard possessed a much greater interfering capacity than virus treated with 5 × 10-3 M mustard, but this was not reflected by a higher level of antigenicity for the former.
The Production of Antibody by Partially Hepatectomized Rats
Authors: Havens W. Paul , Schlosser Mary Ellen , Klatchko Jean
Published: January 2023

The amounts of sheep-cell hemolysin produced by partially hepatectomized rats, laparotomized rats, and normal controls 6 days following the intravenous injection of a suspension of sheep cells were determined. No observable difference was found in the responses of the two control groups; however, the partially hepatectomized rats produced antibody in amounts that were significantly greater statistically than the amounts produced by the controls. The augmented synthesis of antibody by the partially hepatectomized rats suggests the possibility that some specific stimulus associated with removal of a large portion of the liver or its subsequent regeneration might have been operative.
Pneumococcal Antigenic Polysaccharide Substances from Human Tissues
Authors: Felton Lloyd D. , Prescott Benjamin , Kauffmann Gladys , Ottinger Barbara , Bullard H. H. , Binford C. H. , Warner C. G.
Published: January 2023

Summary and Conclusions

In view of the observations that, following a dose of pneumococcus polysaccharide sufficient to produce “immunological paralysis” and a hypersusceptible state, mice retained in their tissues polysaccharide substances which on isolation stimulated a high degree of immunity in other mice against pneumococcus infection, whereas similar polysaccharide fractions from normal animals were lacking in antigenicity, a study has been made of substances similarly isolated from human tissues obtained from 125 individuals at autopsy. This unselected group, ranging in age from newborn to 88 years, included 3 primary lobar pneumonia cases, 2 primary and 23 secondary bronchopneumonia cases, and a miscellaneous group of 97 non-pneumonic fatalities. Ninety per cent of the entire group contained in one or more tissues (liver, spleen, kidney) polysaccharide substances which on isolation stimulated some immunity in mice against pneumococcus infection, especially of types I and/or II. There was some indication that the polysaccharides from pneumonia cases more often stimulated a high degree of immunity than those from non-pneumonia cases; also it was indicated that those from older individuals were more often antigenic than those from younger. It is suggested that accumulation of polysaccharide antigen in human tissues may influence susceptibility to pneumococcus infection and hence perhaps be a contributing factor in the incidence of pneumonia.
Some Considerations of the Antigen Dose-Antibody Response Relationship
Authors: Stevens Kingsley M.
Published: January 2023

Data derived from the literature are presented in support of the 1912 theory of Smith and St. John-Brooks that the antigen dose-antibody response follows the form: K1c1/nAb where K1 is a constant, c is the concentration of the antigen, n is a constant between 1.9 and 3.6 and Ab is the maximum concentration of antibody.

The value of n appears to depend upon the chemical composition of the antigen. For proteins, n is about 1.9, for lipopolysaccharides about 2.6, and for polysaccharides about 3.6. From limited data, this equation appears to hold only at intermediate concentrations of antigen. At low concentrations, n approaches 1, while at high concentrations n approaches infinity.

On the basis of the above equation, certain values for K1 could be calculated, and these are listed.

These findings are consistent with, but do not prove, the concept that the limiting step in antibody production involves an adsorption process.
A Quantitative Study of a Technique of Double Diffusion in Agar
Authors: Preer John R.
Published: January 2023

A technique of double diffusion is described. Warm liquid agar is layered onto serum in tubes and after the agar has cooled and solidified antigen is added. Tubes approximately 1.7 mm inside diameter are used, making it possible to use quantities as small as 0.01 ml. Egg albumin in concentrations as low as approximately 0.0001% could be detected in this way. A theoretical treatment of double diffusion is given which predicts the relation between band position, antigen and antibody concentration, antigen and antibody diffusion coefficients, time, and agar length. Experimental results are compared with these predictions and found to agree in most respects. Zones of precipitation, however, failed to move as rapidly as predicted. In particular, it was shown that band position is linearly related to the logarithm of the ratio of the antigen to antibody concentrations. Bovine gamma globulin and azo-substituted bovine gamma globulin were used to show the interaction between immunologically related proteins in double diffusion. Non-specific effects and the identification of bands were considered.
The Toxic Action of Preparations Containing the Oxygen-Labile Hemolysin of Streptococcus Pyogenes
Authors: Rowen Robert , Bernheimer Alan W.
Published: January 2023

A study has been made of normal mouse plasma and of plasma of mice rendered refractory to the lethal effect of preparations of streptolysin O. Both types of plasma are inhibitory to the in vitro hemolytic action of streptolysin O but the inhibitory capacity of normal mouse plasma is relatively weak. The presence in the blood of refractory mice of a relatively large amount of inhibitory activity accounts for the refractoriness of these mice. The inhibitor in the plasma of refractory mice is not antibody nor does that in the plasma of normal mice appear to be antibody. The properties of the inhibitors in both normal and refractory mouse plasma indicate that the inhibitors are lipoproteins, and that more than one species of lipoprotein appears to be involved in the inhibition.
Poliomyelitis Virus in the Central Nervous Systems of Mice during Prolonged Incubation Periods
Authors: Evans C. A. , Cundy K. R.
Published: January 2023

Summary and Conclusions

In 3 experiments more than 600 mice were injected with an inoculum of Y-SK poliomyelitis virus sufficient to kill approximately three-fourths of the animals in 40 days. Deaths due to viral infection began to occur on the 3rd day and continued well beyond 1 month. Approximately 40% of animals living, and apparently well on the 21st day, succumbed to infection by the 40th day. In 1 experiment in which observations were continued through the 85th day, 1 animal died of viral infection on the 82nd day.

In 2 of the above experiments 20 and 31 mice, apparently normal on the 21st day, were killed at that time and their CNS tissue tested for virus. Of the 51 mice tested, 6 contained virus in a titer (LD50) higher than 10-1 and 11 had smaller amounts of virus. In 7 of these, virus was sufficient to kill only 1 of 5 or 6 test animals injected with a 10% suspension of CNS tissue.

It is concluded that the concentration of infective virus remained low in the CNS of mice undergoing prolonged incubation periods until a few days before death. Then active viral increase occurred. Once multiplication started, it progressed and paralysis and death followed within a few days, probably in much the same time sequence as in animals that died after a short incubation period.

In view of these findings, it appears that the incubation period in this infection encompasses at least 3 distinct phases: In the initial phase virus infects cells and spreads to an unknown extent without much increase of detectable infective virus. Presumably this involves a series of cycles of cellular infection and degeneration, with release of virus and spread of some of the released virus to other cells, the balance being disposed of by undefined mechanisms. Extensive spread of non-infective virus is also a possibility. In a 2nd phase, which may be short or very long, infection remains relatively quiescent with a low concentration of detectable virus in the CNS and no obvious signs of illness of the animal. Whether this is just a prolongation of the first phase or is basically different is uncertain. In the final phase, there is active multiplication of virus with destruction of tissue. Signs of illness appear and progress rapidly until death occurs. It is suggested that the duration of the second phase and the change from second to third phase may be conditioned by physiologic changes in the host.
Flocculation Tests for Brucellosis
Authors: Hunter Charles A. , Colbert Bernice
Published: January 2023

A method of producing a cholesterol-lecithin-brucella extract antigen for a microscopic slide and macroscopic tube flocculation tests has been described. The sensitivity and specificity of the antigen emulsion can be adjusted to conform to the standard antigen emulsion. A method of standardizing the antigen emulsion is described. Data are presented showing that the antigen emulsion is specific. The tests are rapidly performed and the results are clear cut and very easily read. The tests give reproducible results. Heating the serum to 56°C for 30 min reduces the prezone reaction. The agglutination tests give a better pattern after heating the serums.
Experiments on Adsorption in Vitro of Type II Poliomyelitis Virus on Red Cells
Authors: Bautista Gonzalo , Jungeblut Claus W. , Kodza Helen
Published: January 2023

Summary and Conclusions

Human red cells from individual donors, when combined with poliomyelitis virus Type II, differ in their ability to remove virus from the supernatant and to anchor infectious doses on the cellular surface. This virus-removing property shows some relationship with the levels of type-specific neutralizing antibodies in the serum of the donor. Red cells from normal animals do not remove virus from the supernatants of virus-red cell mixtures, but virus removal may be demonstrated with cells from the same animals after their hyperimmunization with the specific antigen. Red cells which do not possess virus-removing capacity, whether from man or animals, acquire the property to remove virus after trypsinization of the erythrocytes. The mechanism of the virus-removing reaction is discussed.
Interaction between Internally Labeled Complement and Specific Precipitates
Authors: Penn Nathan , Haurowitz Felix , Yenson Mutahhar
Published: January 2023

The components of complement (C′) incorporate S35-amino acids in vivo. Small amounts of radioactive S35-protein (C′i) are adsorbed by antigen-antibody precipitates from the decomplemented guinea pig serum; much larger amounts (C′a) from active guinea pig serum. The difference C′a — C′i, denoted as C′d, varies from 0.4 to 0.7% of the total protein-bound radioactivity of the guinea pig sera, and is almost the same at 0 as at 37°C in precipitates washed with 0.15 M saline solution. Much larger amounts of S35-protein are found in precipitates washed with 0.04 M NaCl solution. The loss of adsorbed S35-protein in 0.15 M NaCl solution is prevented by diisopropyl-phosphofluoridate.
Studies of Antibodies Against Organ-Antigens
Authors: Boroff Daniel A. , Meier Rita M. , Heller John H.
Published: January 2023

Antimouse spleen serum exerted a pronounced effect upon mice as evidenced by ruffled fur, apathy and splenomegaly with histologic changes in the spleen elements. The antiserum did not, however, significantly affect the uptake from the circulation of the colloidal carbon by the RES of the mouse. Substitution of CrP32O4 for the carbon revealed that the spleens of the mice treated with AMSS contained at least twice as much radioactive colloid as spleens of the control mice. The increased uptake might be due to either the preferential stimulation of the spleen RES by the AMSS or by the spleen hyperplasia or by both.
Concerning the Mechanism of Complement Action
Authors: Cushman William F. , Becker Elmer L. , Wirtz George
Published: January 2023

Summary and Conclusions

The hypothesis has been advanced that several or all of the components of complement are proteolytic enzymes. It was further proposed that simple chemical substances related to the natural substrates of these supposed enzymes might competitively inhibit the immune hemolysis reaction. Based on these hypotheses over 60 compounds, amino acids, amino acid esters and peptides were tested for their inhibitory action on complement. Three classes of inhibitory compounds were found, sulfhydryl bearing compounds, (cysteine and thioglycollic acid), derivatives of basic amino acids (lysine ethyl ester, TAMe and canavanine) and peptides containing aromatic amino acids. These findings were considered to have supported the hypotheses, but the necessity for further work was stressed. It was further suggested that one of the components of complement might be a proteolytic enzyme either requiring the presence of aromatic amino acids in its substrate, or whose activity is enhanced by substrates containing such acids.
The Effect of Chemical and Physical Treatments of Sera on the Hemolytic Activities and Fixation of Complement Nitrogen by Antigen-Antibody Precipitates
Authors: Weigle William O. , Maurer Paul H.
Published: January 2023

Little relationship was found between the amount of complement N contributed to specific precipitates and either the hemolytic activity of sera or the components of complement present. The complement component probably responsible for the contribution of complement N to immune precipitates was confirmed to be C′1.

Versene and cation exchange resin either decreased or inhibited the contribution of complement N to immune precipitates by guinea pig and human sera. However, these agents had little effect on either the contribution of complement N to immune precipitates or the precipitation of soluble antigen-antibody complexes by rabbit serum.

It was found that urea reversibly inactivated the components of complement. The hemolytic activity and contribution of complement N were either completely or partially inhibited. Almost complete restoration of complement activity of the sera occurred after removal of the urea by dialysis.
Studies on the Serologic Diagnosis of Murine Typhus and Rocky Mountain Spotted Fever
Authors: Hersey David F. , Colvin Mayme C. , Shepard Charles C.
Published: January 2023

Guinea pigs and rabbits were used as experimental animals for a reinvestigation of the serologic diagnosis of murine typhus and RMSF, principally by means of the complement fixation test. In CF block titrations it was observed that method 1 antigens gave results significantly different with early sera than with late sera. With early convalescent or acute sera the antigen titer varied with the concentration of serum; it was uniformly the highest with the lowest dilution of serum tested (1:2) and decreased in a step-wise fashion when the serum was further diluted. With late convalescent sera the antigen titer did not vary in this manner but rather tended to be the same in both the lowest as well as in the highest serum dilution in which CF was observed. With early sera even the lowest dilution of sera did not give as great an antigen titer as the late convalescent sera. These differences in the results of block titrations of early and late specimens make it difficult to define a unit of antigen that will apply both to early and late serum specimens. Antibody was detected earlier in the course of the experimental disease in guinea pigs when increased amounts of method 1 antigen were employed. This was observed consistently in both murine typhus and RMSF.
The Submerged Culture of Mammalian Cells: The Spinner Culture
Authors: McLimans William F. , Davis Eldon V. , Glover Fletcher L. , Rake Geoffrey W.
Published: January 2023

A spinner culture system for the growth of tissue cells in fluid suspension has been described. Actively proliferating mammalian cell suspensions, in volumes of 25 to 400 ml have been established utilizing the prototype “L” cell. Similar, although less extensive, investigations have been conducted with strain HeLa. A 300 to 400 ml “L” cell spinner culture has been continuously maintained for the last 5 months. It is suggested that the described submerged culture system provides a more quantitative tool for investigations relating to the response of the mammalian cell to infectious or pharmacologic agents.
The Effect of Feeding Simple Chemical Allergens to Pregnant Guinea Pigs upon Sensitizability of Their Offspring
Authors: Baer Rudolf L. , Rosenthal Stanley A. , Hagel Blanka
Published: January 2023

Pregnant guinea pigs were fed solutions of picryl chloride (PC) or dinitrochlorobenzene (DNCB) during part of their gestation period. The offspring born to these animals had a slightly, though consistently, lower capacity to become sensitized to the homologous allergen than did the offspring born to mothers not fed the allergen. This slight effect appeared to be specific, since it did not extend to sensitizability to citraconic anhydride (CA), a chemically unrelated allergen.