bluuebunny/crossref_metadata_2025 huggingface dataset:
A Descriptive Theory of Specific Precipitation
Authors: Hershey A. D.
Published: January 2023

In the preceding paper, general expressions are derived for an hypothetical initial equilibrium between multivalent antigen and multivalent antibody, which form the basis for a General theory of precipitation, which postulates a minimal disturbance of the initial equilibrium during aggregation, and a Restricted theory, which specifies the direction of disturbances of the initial equilibrium if antigen and antibody are indeed multivalent. For the special case of lattice-formation, the restricted theory is developed in a preliminary way to permit quantitative description of the composition of precipitates, and more fully to deal with flocculation-times and the meaning of optimal proportions. The restricted theory leads to the concept of selective precipitation,which is probably adequate to explain the small volume effect observed in precipitating systems, and the different effects of excess of either reagent. The relation of structure .to the properties of lattices are considered in connection with the solubility of precipitates and the problem of reversibility of biologic effects of antigen-antibody reactions. Experimental methods are suggested for the measurement of the parameters of lattice-systems, which are three: the maximal valence of antigen, the maximal valence of antibody, and the dissociation-constant of the unit-valence. These, together with concentration-factors, completely define an ideal lattice-system. In the application of the theory to experimental precipitating systems additional parameters such as the homogeneity and functional symmetry of the reactants, and nonspecific associative forces, are considered. In no case do available data clearly show that these influences seriously prejudice the usefulness of the theory. It is likely, however, that such instances will be found. It is suggested that the principal parameter defining the individuality of different immune sera to a given antigen is the dissociation-constant of the specific valence. At present there is no reason to suppose that the diverse properties of different antisera, including their specificity, in any way imply a corresponding diversity of the fundamental immune response. The unit-valence appears to represent an area of contact of the order 10—3 cm2. The relation between the dissociationconstant of the unit-valence and the structure of the antigenic surface is discussed briefly. The dissociation-constant of the immunologic valence is believed to be strongly influenced by associated substances foreign to the specific antibody. The evidence is overwhelmingly in favor of the hypothesis that antibody and antigen are multivalent, and that the maximal valence of antibody is small, probably two. The maximal valence of antigen is probably limited primarily by the physical surface of the molecule. Several definitions of practical usefulness are proposed in part IIc.

The encouragement and instruction continuously offered by Dr. Bronfenbrenner have contributed decisively to the results achieved in this study.
The Toxicity-Indices of Some Basic Antiseptic Substances
Authors: Welch Henry , Brewer Charles M.
Published: January 2023

The relative toxicity of a number of commonly used antiseptics and widely different germicidal substances has been given. By comparing the destruction of the phagocytic activity of the blood with germicidal capacity, their toxic index has been calculated. The diversity of the compounds tested precluded a classification into groups on the basis of relative efficiency. Some of the data were sufficiently provocative to elicit a discussion of certain factors having a possible bearing on relative toxicity.
Selective Agglutination
Authors: Castaneda M. Ruiz
Published: January 2023

A method is described which shows agglutination due to “major” agglutinins in mixtures of homologous and heterologous agglutinogens.

Suitable dilutions of brucella-serum capable of agglutinating both abortus and melitensis to the same titer, show preference for the homologous organism when both antigens are mixed in equal amounts. The test which we have named selective agglutination has been successfully used for the classification of sera from patients suffering from brucellosis and also for differentiation of the brucella strains.

The selective test replaces the absorptive test in routine work to advantage and has been used for diagnostic purposes not only in brucellosis but in typhoidpara-typhoid infections.
The Opsonins of Normal and Immune Sera
Authors: Ecker E. E. , Weisberger A. S. , Pillemer L.
Published: January 2023

A thermolabile antistaphylococcic opsonin is found in active guinea-pig serum. The opsonin operates as a function of its concentration but no zone-phenomenon is noted. The magnitude of opsonization by the fresh serum is the same whether the organism is viable or not, but the opsonic action of active guinea-pig serum is greater for an avirulent strain of staphylococci than for a virulent strain.

The opsonic activity of active guinea-pig serum is optimal in hypotonic solutions and is markedly reduced in hypertonic solutions. Since, however, a staphylococcic rabbit-antiserum operates optimally at a physiological salt solution range, this finding may serve as a means of differentiating between the two sera.

The staphylococcic antiserum shows a typical zone-effect and its active principle is relatively thermostable. The active guinea-pig serum and the antiserum require from 20–30 minutes for optimal activity but during the first few minutes active guinea-pig serum shows a greater opsonic effect than the antiserum.

The addition of active guinea-pig serum to optimal and suboptimal concentrations of the staphylococcic rabbit-antiserum prevents the latter from exerting its full opsonic activity so that the level of opsonization is found in the range of the effect of the added normal serum.

The addition of concentrated antiserum to active guinea-pig serum results in an inhibition of the fresh serum action and the prozone-effect of the antiserum becomes evident.
Studies on Chemical Nature and Standardization of Pollen-Antigen
Authors: Rockwell George E.
Published: January 2023

It has been re-emphasized that the pollen-antigen is destroyed by alkalies and oxidation, but is not destroyed by acids. It has been shown that when concentrated HCl is added to ragweed-pollen-extract it combines with the antigen to form the hydrochloride which precipitates out. This reaction provides a means of separation and purification of the pollen-antigen. Analysis of this purified antigen, shows it to have a minimal molecular weight of 4453 as determined by its sulphur-content. It contains 36 nitrogen-groups, one SH group and is able to combine with 10 molecules of HCl. The pollen-antigen-molecule is pictured as containing 10 basic groups loosely combined with some other substance. This other substance is a hapten or a residue antigen. The purified pollen-antigen is levo-rotatory. An X-ray picture of the pollen-antigen hydrochloride indicates it to be a complex molecule. It is believed that the pollen-antigen is a polypeptide which contains a large per cent of the basic amino-acids (arginine, histidine, lysine). It is shown that 0.0022 microgram of pollen-antigen hydrochloride nitrogen equals 1 Noon unit and 0.0033 microgram equals 1 protein-nitrogen unit.
Studies on Antibody-Antigen Mixtures
Authors: Kulka Anna M.
Published: January 2023

Summary and Conclusions

A method to investigate the effect of Ab-A mixtures on normal living isolated tissue has been described.

Normal living uterine tissue and intestinal strips respond to Ab-A mixtures with immediate histamine-like contractions. This reaction is apparently specific and produces a state of refractoriness which is specific.

The outcome of the reaction depends on a quantitative relationship between antibody and antigen and on another serum-factor which is probably complement.
Toxoids in Active Immunization Against Gas Gangrene
Authors: Kolmer John A. , Rule Anna M.
Published: January 2023

The efficacy of active immunization of guinea pigs and human beings by the administration of plain and especially of alum-precipitated toxoids of Clostridium tetani has now been so well proven as to require no comment or review of the literature. Much less investigation, however, has been devoted to the problem of active immunization of the lower animals and human beings against the principal Clostridia of gas gangrene by their respective toxoids. If this were found safe and effective as immunization against tetanus, it might be possible to effectively immunize human beings simultaneously against tetanus and gangrene with a mixture of their respective toxoids and especially those, as soldiers and civilians, particularly exposed to the risks of accidents and infection of wounds. In this connection it may be stated, however, that the effectiveness of the sulfonamide compounds in the prevention of infection of war wounds, especially by the prompt topical application of sulfanilamide, has greatly lowered the incidence of infections due to the pyogenic microorganisms and of tetanus and gangrene as well.
Studies on the Stabilizing Diluent for Old Tuberculin
Authors: Gottschall R. Y. , Koppa T. M. , Tripp J. T.
Published: January 2023

Edematous reactions in the guinea pig after injection of a tuberculin-diluent containing borax-boric acid buffer, gum acacia and phenol are due to the phenol.

Sensitivity to gum acacia could not be demonstrated by the methods employed.

Of 1624 human subjects tested with the diluent, none showed reactions that did not disappear within 72 hours. The reactions that were elicited could not be interpreted as positive tuberculin-reactions.

The diluent does not cause a significantly greater number of reactions than does phenolized saline.

There is no appreciable difference between the kind or number of positive reactions when old tuberculin diluted in the stabilizing diluent is compared with tuberculin diluted in phenolized saline.
Electrophoresis of Normal Rabbit-Serum
Authors: Sharp D. G. , Taylor A. R. , Beard Dorothy , Beard J. W.
Published: January 2023

Electrophoretic analysis has been made of 12 normal rabbit-sera by the moving-boundary-method of Tiselius. Mobility-measurements at pH 7.8, 0.2 ionic strength, and 1 C show coefficients of variation for the individual components somewhat less than the analogous findings with a similar series of normal human plasmas.

Composition of the sera is reported in terms of the respective areas under the various component-peaks of the refractive index-gradient-curves produced by the method of crossed slits. Gamma-globulin areas were subject to the greatest variation, the maximum being that between 13 and 29½ per cent of the total protein. The variation in amount of beta-globulin was of less magnitude, but in several instances the boundary split into 2 and possibly 3 parts which varied greatly in relative size from one experiment to the next.

The alpha-globulin of rabbit-serum moved only slightly slower than the albumin, and good separation was difficult to obtain, particularly in cases where the albumin-content was high. Separate area-measurements were possible in 3 cases where the alpha-globulin constituted 5.5, 7.5, and 7.9 per cent of the total protein.

The globulin-content of these 12 sera was about 10 per cent higher than that reported for another group of normal rabbits by Seibert (3). It is possible that such differences may be due to species-variation or to differences in diet. Nevertheless, the individual variations found here are much greater than this group-variation, emphasizing the difficulty of establishing a normal pattern.
A Study of Four Antigenic Components of Rabbits' Erythrocytes
Authors: Knopfmacher H. P.
Published: January 2023

Levine and Landsteiner (1) were the first to identify an isohemagglutinogen in rabbits, later called H1. A second agglutinogen of rabbits' red blood corpuscles was discovered by Fischer and Klinkhart (2), who were also able to demonstrate a two-receptor system (3). On the basis of the presence or absence of the antigens rabbits could be classified in any of the 4 blood groups O, H1, H2, and H1H2. More recent studies by Fischer (4) have disclosed the existence of 3 more hemagglutinogens, H3, H4, and H5.

Castle and Keeler (5) studied the inheritance of antigens H1 and H2 and found that they were transmitted by three allelomorphic genes, two of which (H1 and H2) appeared to be dominant over the third one (O).

On the basis of their isoimmunization experiments Levine and Landsteiner (6) postulated the presence of a great number of additional agglutinogens in rabbits' blood corpuscles.
The Weil-Felix Reaction in Patients with Proteus and Pseudomonas Aeruginosa Infections
Authors: Dammin Gustave J. , Billings F. Tremaine
Published: January 2023

A minor antigen has been demonstrated which is common to human strains of Proteus and Pseudomonas aeruginosa and to the “X” strains of Proteus routinely employed in the Weil-Felix test. The existence of this common minor antigen explains the positive Weil-Felix reactions exhibited by patients infected with Proteus and Pseudomonas aeruginosa. When tested with the Weil-Felix antigens, the sera of these patients show an agglutinative pattern different from that found in the rickettsial diseases. The agglutinative titer is usually lowest for Proteus OX19, is somewhat higher for Proteus OX2, and is highest for Proteus OXK. These findings are in agreement with the results of absorptive experiments which indicate that the strains of Proteus isolated from patients are most closely related antigenically to Proteus OXK.
Studies on the Specific Mechanism of Serum Sickness
Authors: Karelitz Samuel , Stempien Stephen S.
Published: January 2023

The blood serum of individuals convalescing from serum sickness following treatment with horse serum is designated as S.S.C.S. or Serum Sickness Convalescent Serum. This S.S.C.S. possesses the property of inducing a reaction in horse-serum-treated patients which is milder than but otherwise clinically similar to serum sickness. By injecting 2–10 ml of the S.S.C.S. intravenously into 62 patients treated with horse serum, 65 per cent developed this reaction. We have named this reaction “passive serum sickness,” and believe it more appropriate than “inverse serum sickness” offered by Voss. Evidence has been presented which indicates that passive serum sickness is a specific reaction of a horse-serum-treated patient to S.S.C.S. and is similar to serum sickness. An episode of passive serum sickness may modify the subsequent course of the horse-serum-treated patient. It may hasten the onset of serum sickness, it may shorten the course of the serum sickness, and may even prevent its occurrence. This did not occur sufficiently often in our cases to warrant recommending its routine use as prophylaxis against serum sickness. Further study may alter this opinion.
Studies on the Specific Mechanism of Serum Sickness
Authors: Karelitz Samuel
Published: January 2023

Passive serum sickness (1) is produced by the intravenous injection of 2–10 ml of S.S.C.S. into patients who 8 hours to 9 days before were injected with horse serum. If the S.S.C.S. is injected intravenously very soon after the patient received the therapeutic horse serum, passive serum sickness does not occur. To induce passive serum sickness, some time must elapse between the treatment with horse serum and the injection of the S.S.C.S. While attempting to determine the minimal duration of this period we noted that if the interval was 5–60 minutes, passive serum sickness did not occur. Neither did the ordinary serum sickness occur in the first four patients so treated, even though the incidence of serum sickness following the use of this lot of scarlet fever antitoxin without S.S.C.S. was quite high. These results prompted us to study the efficacy of S.S.C.S. in modifying and preventing serum sickness when both the horse serum and S.S.C.S. were injected simultaneously.
The Effect of the Amount of Antigen on Antitoxin-Formation During the Primary and Secondary Immunizations
Authors: Freund Jules , Bonanto Mary V.
Published: January 2023

Groups of rabbits were immunized by two courses of intravenous injections of alum precipitated diphtheric toxoid; the two courses were one or more months apart. One injection after the rest period gave far greater antibody response than could be obtained by the first course of immunization.

During the first course the response of rabbits to different doses of antigens was almost the same but during the second course more antitoxin was formed after the injection of larger amounts of antigens up to 5000 Lf per injection. The rise and fall of antitoxin titers were the sharpest with the largest doses of antigen. The accumulation of stimuli in the group with small doses did not produce as high titers as one single injection of 1000 Lf.
The Influence of Non-Specific Protein on the Heat Inactivation of Antibody to Pneumococcal Polysaccharide
Authors: Jennings Robert K. , Smith Louis Despain
Published: January 2023

Water-insoluble globulin from a sample of Type I antipneumococcal horse serum was found to be more heat resistant than the parent serum as regards retention of specific precipitability. Restoration of the serum components removed in purification, or addition of whole serum to the water insoluble-globulin solution, resulted in mixtures which were inactivated under conditions which did not inactivate the antibody alone. Heating the water-insoluble globulin and the other serum components separately before mixing did not interfere with specific precipitation. The ability to assist in heat inactivation of antipneumococcal antibody appeared to be a property associated primarily with the non-antibody serum globulin. Casein, also, possessed this property to a marked degree. Gelatin, albumin, myogen, pectin, gum arabic, and heterologous polysaccharide had no effect upon the heat-inactivation of antibody.
An Effect of Temperature Upon Antibody-Production in Fish
Authors: Cushing J. E.
Published: January 2023

A study was made upon the rate of production of agglutinins against sea urchin sperm in carp and gold fish held at two different temperatures (15 and 28 degrees). The fish, four of each kind at each temperature, were bled every few days from the heart and agglutinative tests made on their sera. These showed that the antibody-titer of the fish kept in the warm tank rose at least four days sooner than that of those kept in the cold tank. This indicates, in agreement with other work, that temperature does influence the rate of antibody-production in cold-blooded vertebrates.
Increase of Specific and Non-Specific Resistance by the Transplantation of Attenuated Tubercle Bacilli Nodules
Authors: Ascoli Alberto
Published: January 2023

Post-mortem examination revealed that the calves no. 131 and 132, recipients of the 9-day-old nodules showed no specific lesions after having been injected intravenously with virulent tubercle bacilli. In the control calf, untreated before the injection of the virulent bacilli, definite processes of miliary tuberculosis were found in the lungs and the thoracic lymph nodes. In calf no. 10,793 from which the nodules had been removed, there was a very pronounced enlargement of the thoracic and pharyngeal lymph nodes, but specific lesions could not be seen either with the naked eye or under the microscope. The degree of resistance left after removal of the two nodules from calf no. 10,793, which had received 10 cg of the less attenuated I.V.A. vaccine, seemed to be greater than the degree of resistance left in a calf from which a nodule formed by subcutaneous injection of only 5 cg of B.C.G. had been removed.
The Effect of Enzymic Digestion Upon the Antigenic Properties of Antitoxic and Normal Horse Plasmas
Authors: Kass Edward H. , Scherago M. , Weaver R. H.
Published: January 2023

The action of the enzymes, Aspergillus oryzae diastase, malt-diastase, and pepsin on antitoxic and normal horse plasmas has been studied. All three enzymes have been found to purify antitoxic plasmas and also to render the antitoxic molecule resistant to subsequent heat-treatment. Evidence has been presented that the antitoxic molecule decreases in size as purification proceeds, and it is suggested that the process of purification of antitoxins by the enzymes studied is essentially a proteolytic one. Normal plasmas appear to be much less resistant to enzymic action than are antitoxic plasmas.

Antigenic studies of the digested products by means of the Schultz-Dale technic have revealed that the digested antitoxins are antigenically closely allied, regardless of which of the three enzymes is used for digestion.

Animals sensitized to undigested normal or undigested antitoxic plasmas do not react to digested antitoxic nor to digested normal plasmas. Animals sensitized to unheated digested plasmas react not only to the homologous antigens but also to undigested plasma. Animals sensitized to digested antitoxic plasmas react to both digested antitoxic and digested normal plasmas, whereas animals sensitized to digested normal plasmas do not react to digested antitoxic plasmas. Heat-treatment affects the antigenic character of the digested antitoxins. Animals sensitized to heat-treated antitoxin fail to react to digested, unheated antitoxin, but do react to undigested, unheated normal or antitoxic serum protein, and also to digested, heated antitoxin.
Molecular Kinetic Analyses and Serological Specificities of Polysaccharides Isolated from Filtrates of the Human Tubercle Bacillus and Related Species
Authors: Tennent David M. , Watson Dennis W.
Published: January 2023

Polysaccharides from the culture-filtrates of the human-, avian-, and bovine-type tubercle bacilli, and of the leprosy bacillus and B. phlei have been isolated by electrophoresis. The mobilities, the sedimentation- and diffusion-constants, and the serological specificities of these fractions have been determined. The molecular weights of the polysaccharides from human-type tubercle bacilli and from B. phlei, calculated from the sedimentation- and diffusion-constants, were found to be 7300; that of the polysaccharide from avian-type tubercle bacilli was found to be 7200; and that of the leprosy-bacillus polysaccharide, 2500. The dissymmetry-numbers, and the ratios of major to minor axis indicate that the leprosy-bacillus polysaccharide is spherical, and that the polysaccharide from tuberculin from human-type tubercle bacilli is not greatly elongated. All of the polysaccharides gave high titers in precipitation with anti-H37 horse serum. These polysaccharides are genus-specific rather than species-specific.
Specificity of the Antibody Response of Human Beings to Strains of Influenza Virus
Authors: Bodily H. L. , Eaton M. D.
Published: January 2023

Acute and convalescent sera from cases of influenza A have been tested for neutralizing antibodies to PR8, W.S., and Melbourne strains of influenza A, the Lee strain of influenza B, and the swine influenza virus by the chicken-cell agglutination method. Considerable specificity was demonstrated between PR8 and W.S. and swine influenza. It was also indicated that the strain-specificity was not limited to those producing poor rises to PR8, but occurred in some cases producing good rises to PR8. Mouse neutralization tests on selected cases confirmed the results obtained by the agglutinative test.

Persons vaccinated with influenza A vaccines whose sera were tested with the same virus strains were found to be somewhat more specific in their antibody response to strains PR8, W.S., and swine than were the sera of infected individuals. This apparent increase of specificity may be due, in part at least, to the fact that the response to the vaccine was not as great as was the response to an attack of influenza A.

Sera of several persons infected or vaccinated with influenza A showed also an output of antibodies to the Lee strain of influenza B. Some of these apparent increases in reactivity may have been due, however, to the partial destruction of antibodies by a contaminant in the preliminary serum specimens.

A few individuals vaccinated with active Melbourne vaccine showed a better response to Melbourne than to PR8. Conversely, those vaccinated with PR8-distemper virus vaccine responded better to PR8 than to Melbourne.
In Vitro Titration of Horse Sera Containing Both Vibrion Septique and Perfringens Antitoxin
Authors: Koerber Walter L. , Alture-Werber E.
Published: January 2023

Trial horse bleedings and concentrated sera containing both vibrion septique and perfringens antitoxin can be titrated for each antitoxin separately by in vitro methods. For determination of vibrion septique antitoxin a hemolytic test is described which yields satisfactory results in routine testing of antitoxin. The presence of perfringens antibodies does not interfere with the vibrion septique hemolysin-antihemolysin reaction. Satisfactory results are also obtained in the perfringens in vitro titration of antitoxin by the egg yolk reaction in spite of the presence of vibrion septique antibodies in the same serum.

The authors are grateful to Dr. W. E. Bunney for his kind interest and helpful criticism.
Studies on Precipitin-Production and Anaphylactic Sensitization in Guinea-Pigs
Authors: Cohen Harold R. , Mosko Milton M.
Published: January 2023

It has been generally considered that the guinea-pig is a poor producer of precipitins (1, 2). Recently, Colwell and Youmans (3) stated that they were unable to detect circulating precipitins in guinea-pigs given multiple intraäbdominal injections of crystalline egg albumin, but were able to obtain precipitins for sheep serum proteins. It is, however, recognized that the guinea-pig is highly susceptible to anaphylactic sensitization.

The possibility that the method of administration of the antigen was a factor influencing the ability of this species of animal to produce precipitins was considered. Groups of guinea-pigs were injected with crystalline egg-albumin either by the intraäbdominal or intracardial route, or given intramuscular injections of the antigen adsorbed on aluminum-hydroxide-cream (4).

Procedure. (a) Adult guinea-pigs, weighing 350–500 grams, were used. Thirteen animals were injected intraäbdominally, four times at 3-day intervals with a solution containing 5 mg (0.5 ml of a 1 per cent solution) of 4-times-recrystallized egg-albumin.
Influence of Benzene-Poisoning Upon Streptococcal Infections in Rabbits
Authors: Schnitzer R. J.
Published: January 2023

In rabbits immunized by one to three intracutaneous injections with living culture of streptococci, an exposure to benzene with the following leucopenia did not consistently prevent the fixation of streptococci in an intracutaneous focus, as it is the case in normal rabbits. While the infection was always fatal for non-immunized animals poisoned with benzene, approximately 70 per cent of the immunized rabbits survived. The same results were obtained in rabbits poisoned with benzene and sensitized intracutaneously with type-specific antistreptococcal serum previous to the infection. The local lesion in the animals receiving immune serum locally did not react like an inflamed area to the trypan blue test. From these observations the conclusion is drawn that after an active or passive immunization the local fixation of streptococci should mainly be attributed to the action of antibodies.
The Effect of Alcoholic Intoxication Upon Acquired Resistance to Pneumococcal Infection in Rabbits
Authors: Lushbaugh Clarence C.
Published: January 2023

The effects of alcoholic intoxication upon immunological processes have been investigated since Koch (1), in 1884, observed higher fatality-rates during cholera-epidemics among excessive users of alcohol, and concluded, therefore, that alcoholic intoxication depresses the immune mechanisms in man. Although an extensive literature on this subject has developed since then, no attempt to review it will be made in this paper, as this has been well done recently (2).

The present study of the effect of alcoholic intoxication in the rabbit upon acquired resistance to pneumococcal infection was undertaken in an effort to determine (1) in what ways alcoholic intoxication might influence the mechanisms of active immunity, and (2) to what extent large amounts of antibody might tend to counteract the loss of resistance caused by alcohol. Previous investigations have neglected this phase of the problem and hence have failed to supply important information necessary for the adequate treatment of infections in alcoholic patients.
Complement Fixation for Lymphogranuloma Venereum and for Psittacosis with Frei Reactions among Pneumonia Patients
Authors: Levine Sonnia , Holder Ernest C. , Bullowa Jesse G. M.
Published: January 2023

Complement fixation with Lygranum antigen occurred with sera from Freipositive patients who showed symptoms of lymphogranuloma venereum infection and with sera from Frei-positive patients who had neither symptoms nor a past history of infection. Eighteen Frei-positive reactors, without manifest disease, were found in one hundred and seventy-five pneumococcic pneumonia patients. Cross complement-fixation reactions have been demonstrated with the antigens of lymphogranuloma venereum and psittacosis viruses. Therefore, for the diagnosis of lymphogranuloma venereum, complement fixation must be corroborated by a positive Frei test. In the absence of a positive Frei test, positive complement fixation with Lygranum antigen may indicate the presence of psittacosis or allied viral infection.
The Complementary Activity of Mouse-Serum
Authors: Brown Gordon C.
Published: January 2023

The serum of the mouse differs from that of most animals in that it is without complementary activity. Its serum fails to hemolyze sensitized sheep-cells. Ritz in 1911 (1) observed that mouse-serum contains one component of complement called the midpiece but that the endpiece is missing. This phenomenon is analogous to that given by the fresh serum from a strain of complement-deficient guinea-pigs first reported by Moore (2). A thorough study of this serum by Coca (3), Ecker (4) and Hyde (5, 6) has shown that it is activated in a hemolytic system by very small amounts of heated serum from man or the normal guinea-pig. Thus, the midpiece and endpiece of complement are normally present in this serum but the third complement-component, the heat-resistant or yeast-absorbed component, is missing.

The separation by various methods of guinea-pig complement into several components has been described by Leifmann (7, 8), Browning and Mackie (9) and Whitehead, Gordon, and Wormall (10, 11).
The Biological Assay of Tetanus-Toxoid
Authors: Greenberg L. , Morrell C. A. , Gibbard J.
Published: January 2023

Dosage-response-curves have been employed in comparing the potency of various tetanus-toxoids. The potency of the preparations was expressed in terms of a standard, thus obviating the use of animal standards. The method permits of the computation of the limits of error from data supplied by the test. Mice and guinea-pigs were found to be equally satisfactory test-animals as judged by the limits of error and by assay of the same material on both species. The method demonstrated that there was considerable variation in the protective qualities of a number of tetanus-toxoids purchased on the market.
Effect of Temperature of Inactivation of Human, Rabbit, and Guinea-Pig Serum Upon the Hemolytic Activity of Complement
Authors: Hazen Elizabeth L.
Published: January 2023

The effect upon the hemolytic activity of complement of preliminary incubation (4 hours, 3 to 6 C) in the presence of human, guinea-pig, and rabbit sera inactivated at various temperatures is discussed. Varying degrees of inhibition or activation of the complement were demonstrated depending upon the temperature of inactivation of the sera. The amount of complement, in terms of hemolytic units, required for 50-per-cent hemolysis and the rate at which the number of units changed varied inversely with the temperature of inactivation of the sera. The inhibitory effect of the sera appeared to be due to properties, relatively heat-labile, and the activating effect to relatively heat-stabile properties. The effect of temperature of inactivation upon the specific activity of syphilitic sera as determined by quantitative changes in the activity of complement is also discussed. The specific activity of the sera varied with the temperature, and was approximately maximal at 55 to 57 C. The quantitative changes in the activity of the complement in the presence of sera inactivated at 59 C were not below their value at 53 C; therefore it does not appear that the specific activity of the sera was decreased by temperatures of 53 to 59 C. Although a definite conclusion cannot be drawn from so limited a study, these observations suggest that within limits, the differences in the activity of sera following inactivation are due not to the destruction of antibody by heat, but to other properties of the heated sera that affect the activity of complement.
The Immunochemistry of Allergens
Authors: Coulson E. J. , Spies Joseph R. , Stevens Henry
Published: January 2023

Antigenic relationships of previously described electrophoretic fractionation products of the allergenic protein-carbohydrate fraction CS-1A from cottonseed were studied by the Dale method. Fraction CS-51R (picric acid-precipitable cathodic fraction) was found to be antigenically indistinguishable from CS-56R (picric acid-precipitable anodic fraction). Fraction CS-56S, separated from the mother liquor in the picric acid fractionation of the anodic fraction, was found to contain antigen unrelated to CS-51R or CS-56R. A refractionated carbohydrate-free cathodic fraction, CS-60C, was antigenically indistinguishable from CS-51R. Hence carbohydrate plays no apparent role in determining antigenic specificity.

The antigenic specificity of fractions CS-51R and CS-56R was not altered by the procedure of isolation. Thus they appear to be preformed native proteins.
Studies of Antipneumococcal Serum
Authors: Rice Christine E.
Published: January 2023

These experiments with sixty-six lots of antipneumococcal rabbit-sera have shown that the relative proportion of homologous type-specific carbohydrate and antiserum required for maximal fixation of complement in tests incubated for twenty-four hours at 3–6 C, designated as α3–6, was in all but one instance lower than the proportion of antigen: serum needed for maximal absorption, that is, for the most complete removal by precipitation of the complement-fixing and precipitative activity from the serum.

When antigen and antiserum were mixed in the proportions indicated as necessary for maximal absorption, the amount of complement fixed was similar to or significantly less than that observed when the lower antigen: serum proportion, α3–6, was used. Thus, these antisera appeared to have a greater combining capacity with antigen than was indicated by the antigen:serum ratio α3–6. Why this increased combination of antigen and antibody was not accompanied by a corresponding increase in the amount of complement fixed during twenty-four hours' incubation at 3–6 C remains a matter for conjecture.

Whereas, in precipitative tests, the intermediate zone appeared as a region in which the supernates exhibited activity neither with added antigen nor with added antiserum, in complement-fixation tests of the same supernates, the presence of both excess antigen and residual antibody was usually demonstrable. The extent of the intermediate zone in which appreciable complement-fixing activity with both added antigen and antiserum could be detected varied considerably for different antisera. It was narrowest for a number of individual bleedings, unheated previous to absorption; broadest for certain lots of processed sera concentrated by chemical methods. Irregularities were noted in the behavior of some seven antigen-preparations.

For ten of the sixty-six antisera tested, α3–6 fell in the region of slight antibodyexcess; for forty-three, in the intermediate zone toward or at the beginning of the zone of antibody-excess; for twelve, in the intermediate zone toward the region of antigen-excess; and for one serum, definitely in the zone of antigenexcess, as denoted by complement-fixation. In respect to the relation of α3–6 to the intermediate zone, the behavior of concentrated sera resembled that of the majority of unconcentrated sera. In most instances, therefore, tests of the complement-fixing activity of supernates from mixtures of antigen and antiserum in the proportion represented by α3–6 indicated the presence of a definite excess of antibody and a slight excess of antigen, whereas precipitative tests on the same supernates were consistently negative.
Review
Authors: Bornstein S.
Published: January 2023

The Salmonella Group. Definition and Classification. The genus Salmonella comprises gram-negative and non-spore-forming bacilli that, as a rule, are motile by means of peritrichous flagella, grow well on ordinary culture media, produce acid and gas from mannitol, maltose, glucose and sorbitol, do not ferment lactose, sucrose and salicin, do not form indole from peptone and do not liquefy gelatin. They have one common quality: “All the known species are pathogenic for man, animals or both” [White, 1929] (367). Though some of the types have not yet been isolated from man, it is fair to assume that all of them are at least potentially pathogenic for man.

Because of the importance for human and veterinary pathology, there exists a need for a rapid and simple method of identifying cultures as belonging to the Salmonella group. No single criterion is available by which this can be done.
The Chemistry of Pollen-Extracts
Authors: Brown Ethan Allan , Benotti Norbert
Published: January 2023

Cooke and Stull (1, 2) employed phosphotungstic acid in hydrochloric acid for the standardization of pollen-extracts, and established a protein-nitrogen unit which was taken as equal to 0.00001 mg of nitrogen per ml of extract. This method has become one of those most widely used for the standardization of extracts used in allergic practice and research.

If the actual active substance in pollen-extract were known, then methods for its exact measurement might be evolved. Since, however, its nature is not specifically known, allergists are forced to accept various procedures which, at best, give only an approximation of the relative strength of successive extracts. The experiments described below point to the fact that the method of Cooke and Stull, considered the least inexact of the various procedures, is not scientifically acceptable. The total of so-called protein-nitrogen units said to be measured by this method in any one extract varies with a number of physical and chemical factors not usually controlled.
The Mouse-Protective Test as a Uniform Method of Assay for Antibacterial and Antiviral Sera
Authors: Little Paul A.
Published: January 2023

The mouse-protective technic described by Felton for evaluation of antipneumococcal sera has been used in determining potencies of antisera prepared by immunizing animals with Pasteurella multocida, Erysipelothrix rhusiopathiae, Streptococcus agalactiae (O90S), Clostridium chauvei; and the eastern and western types of the virus of equine encephalomyelitis. The results of the tests have revealed consistent differences in the length of time required for fatal consequences when similar lethal quantities of the different species of infecting agent were used. Nevertheless the protective endpoints were as clearly discernible in antisera specific for one organism as in antisera specific for another, and the mice receiving non-protective doses of serum died as regularly from infection with organisms requiring five days to kill as from infection with organisms requiring only one day. Observation-periods of 5 days for Cl. chauvei, P. multocida, types 1 and 2 and S. agalactiae, of 7 days for E. rhusiopathiae and the virus of eastern encephalomyelitis and of 9 days for the virus of western encephalomyelitis were considered to be satisfactory.
Immunochemical Studies on Human Serum
Authors: Dozois T. F. , Seifter S. , Ecker E. E.
Published: January 2023

The bactericidal action of human serum against V. comma, strain 82, is a result of the combined action of antibody and complement. The bactericidal action of human complement against this vibrio is destroyed by the inactivation of any one of the four complement components. Such a complement is said to be specifically inactivated. Bactericidal action is restored to a specifically inactivated complement (siC′) by the addition to it of the particular complement component which it lacks. Bactericidal action of human complement against this vibrio is fortified in particular by the addition of the “pH=5.4—μ 0.02 supernate.” All evidence in this paper points to the identity of bactericidal and hemolytic complements in human serum.
Histamine-Protein Complexes: Synthesis and Immunologic Investigation
Authors: Fell Norbert , Rodney Gertrude , Marshall Donald E.
Published: January 2023

Histamine antigens have been prepared by coupling diazotized p-aminobenzoyl-histamine to various proteins. Hyperimmunization of animals with these compounds produced antibodies that were partially specific for the histamine hapten. The immunized animals displayed a marked degree of resistance to anaphylaxis.
Immunological Studies of Pollinosis
Authors: Loveless Mary Hewitt
Published: January 2023

Summary and Discussion

In attempting to elicit the enhanced immunological response in hay-fever patients, it was found that a primary series of injections with ragweed-extract so educated its recipients that they responded to later doses more quickly and vigorously, providing an adequate period of freedom from treatment had been allowed. In general, longer periods of rest and lower resting titers were followed by better immune responses than were shorter periods and higher titers. Secondary stimuli given rapidly proved to be more effective than the same-sized doses administered over a longer treatment-period. A primary course of 50,000 units produced higher antibody-concentrations and better clinical results than did an initial series of only 3500 units. Patients receiving the larger dosage their first year appeared to respond more favorably to secondary stimuli than did the other group.

These findings suggest that the average patient will fare better if he is treated intensively for several months his first year. An extensive primary course will offer a good opportunity for protective amounts of thermostable antibody to be acquired by his blood and shock-tissues previous to the season of pollination. Periodical tests for immunity, performed at intervals during treatment and at the peak of the pollinating season, will indicate the patient's responsiveness and approximately at what level of immunity he will be clinically comfortable when there is pollen in the air. The goal of secondary stimulation can then be this degree of antibody-formation. As previously suggested, the serum, skin, or shock-tissue may be tested for immunity, the conjunctival test being the simplest.

A subsequent publication will show that this approach to the management of hay fever will often make it possible to give a satisfactory degree of clinical immunity in a few days or weeks, once the patient has been “educated” by an initial series of injections and a rest-period.
Dermal Supersensitivity, Heat-Labile, and Heat-Stabile Antibody Against Ragweed in Cattle
Authors: Weil A. J. , Reddin L.
Published: January 2023

Evidence has been given of: the existence of dermal supersensitivity in cattle to ragweed-pollen,the presence of an agent (reagin) in the serum of such animals that permits passive transfer of supersensitivity, and which is destroyed by heating for 2 hours at 56 C,the production of a neutralizing antibody in cattle experimentally injected with ragweed-pollen antigen, which is not impaired in its activity by heating the serum for 2 hours at 56 C,a similar neutralizing effect can be obtained with the serum of rabbits that had been injected with ragweed-pollen,the sera of immunized cows may also have complement-fixing qualities.

The similarity of these findings to the ones in human allergy has been pointed out, and the implications on our conception of the mechanism of supersensitivity in mammals have been discussed.
Restoration of Activity of Neutralized Biologic Agents by Removal of the Antibody with Papain
Authors: Kalmanson G. M. , Bronfenbrenner J.
Published: January 2023

Summary and Conclusions

It has been found that proteolytic enzymes such as crystalline pepsin, trypsin, chymotrypsin, and activated crude papain have no effect on the relatively pure coliphage. The failure of the ribonuclease to inactivate it is in accord with the finding that phage contains only 0.07 per cent of phosphorus and, therefore, probably is not a nucleoprotein. Trypsin and chymotrypsin have been found to have no effect on phage-antibody. Pepsin very slowly, and papain very rapidly, destroy the antiphage. When bacteriophage is neutralized (inactivated) by specific antibody, digestion of this antibody by papain restores the phage-activity. The length of contact of phage with antibody prior to digestion with papain has been found not to affect reactivation. On the other hand, the amount of antibody combined with phage determines the outcome of attempts at reactivation. If phage-particle is combined with just enough antibody to neutralize it, it can be reactivated, while if the phage is overneutralized it cannot be reactivated by digestion with papain. This finding has been explained by the failure of the papain to digest the antibody-molecule completely (as distinct from destroying antibody-function), as indicated by the fact that digested reactivable, as well as unreactivable, mixtures sensitize guinea pigs to rabbit serum, while only the reactivable mixtures stimulate production of antiphage. Botulinal toxin neutralized by antitoxin has been reactivated by papain. The resemblance to phage is even more complete in the fact that overneutralized toxin cannot be reactivated. Free specific polysaccharide may be obtained from specific floccules by digestion with papain. However, pneumococci, even when sensitized with excess of antibody, can infect mice if antibody is digested with papain. The reasons for differences in reactivability of the phage- and toxin-systems on one hand and the pneumococcus on the other have been discussed. It has been found that digested (unreactivated) overneutralized phage does not elicit the production of antiphage, and this fact is discussed in relation to the possible use of neutralized viruses for immunization.
The Effect Produced in Vitro by Vitamin C on the Toxic and Antigenic Properties of Diphtherial Toxin
Authors: Willison Frances E.
Published: January 2023

Diphtherial toxin under limited conditions at pH values which are noninjurious, is inactivated by vitamin C. Evidence supports the view that oxidation of the toxic molecule occurs. Furthermore, toxin-vitamin mixtures are unsatisfactory immunizing agents inasmuch as loss of toxicity is accompanied by a corresponding loss of antigenic properties.
Quantitative Studies of Sulfonamide Inhibitors
Authors: Rantz Lowell A. , Kirby William M. M. , Dole Georgiana
Published: January 2023

The effects of peptone, yeast extract, amino acids, glucose, and the temperature of incubation on sulfonamide bacteriostasis have been studied. Variation of the temperature of incubation away from an optimum enhanced sulfonamide action. The antisulfonamide action of peptone and yeast extract was closely related to their ability to improve the environment of the test organism. An increase in the concentration of amino acids resulted in truesulfonamide inhibition. The significance of these results has been discussed.