bluuebunny/crossref_metadata_2025 huggingface dataset:
The Formation of Precipitin for the Group a Specific Carbohydrate of Streptococcus Hemolyticus in Rabbits Injected Intravenously and Subcutaneously
Authors: Seegal David , Heidelberger Michael , Jost Elizabeth L.
Published: January 2023

The variations in antibody formation following the injection of bacterial suspensions by different routes have been studied by a number of workers, but few of these reports have dealt with antibodies to specific bacterial carbohydrates. Julianelle (1) studied the latter problem in 1930 and found that 53 out of 60 rabbits immunized by repeated intracutaneous injections of small doses of heat-killed type I pneumococci failed to develop type-specific antibodies in their serum, while the remaining seven rabbits showed a very low titier of these antibodies. The sera of all sixty animals contained a high titer of antibody to the speciesspecific protein of Pneumococcus. The animals which failed to develop the type-specific carbohydrate antibody after intracutaneous injection still possessed “the ability to form type-specific antibodies when they were subsequently given intravenous inoculations of type-specific pneumococci.” Francis and Tillett (2) subsequently reported similar results.
Duration of the Immunity Produced in Rats by Feeding the Pneumococcus, Type 1
Authors: Ross Victor
Published: January 2023

Discussion and Summary

The noteworthy result of this investigation is the fact that the prompt appearance of immunity in rats produced by a single small feeding or by several small feedings of pneumococci is followed by an only slightly less prompt loss of this protection. Although in some experiments a small proportion of rats may still be immune after eight or ten days, others may lose their immunity in five days. Even a large number of small doses does not appear to extend the duration after the last dose materially beyond that observed after a single ingestion. A few large feedings (bacteria from 50 cc. on each of three days) prolongs the period of increased resistance so that small numbers of rats are still immune fifteen days after the last dose. When a large number (16) of large feedings is employed the period of immunity is noticeably extended, half the animals still being resistant after a month and a small percentage after two months. Wide variations, however, have been observed when similar dosages have been employed. Experiments 11 and 12 illustrate this. Recent repetitions of the experiment referred to above, in which the tissues of rats killed by the pneumococcus were fed, also disclosed variations in the duration of the immunity. In no case was a period of four months again observed. We have also found that the antibodies which appear after oral administration of pneumococcus vaccines to humans will, in some persons, disappear in six months, whereas in others they remain for at least twenty-three to twenty-four months.

When live organisms are fed, the protection appears to be more durable than when dead pneumococci are used. The difference is apparent when the number of feedings is small. Perhaps some of the bacteria escape the solvent action of the bile, establish a temporary foothold, and in this manner furnish additional antigenic material for a time. When the number of doses is large, the difference is less noticeable.

Judging by the data obtained with rats over a period of several years, and by the protective antibody tests performed on humans, neither a more rapid response nor a higher degree of immunity, nor a more lasting one has been observed with the use of one kind of non-living material than with another. However, when only 1 or 2 doses of desiccated vaccine are employed and the product is not emulsified in water before administering it the response is likely to be less uniform than when any of the other forms is used.

When the immunity lapses a single new feeding restores it. When this fails it is due to a large increase in the size of the animal in the interval between the tests. Administering a larger dose will elicit, in such cases, a renewed resistance.
The Antigenic Relationship of the Alcoholsoluble Fractions of Brain and Testicle
Authors: Lewis Julian H.
Published: January 2023

Anti-brain sera react with the alcoholic extracts of testicle and anti-testicle sera react with alcoholic extracts of brain. The interaction of brain and testicle is independent of species as anti-brain and anti-testicle sera will react with alcoholic extracts of brain and testicle of different species. Anti-testicle sera, like anti-brain sera, do not react with the alcoholic extract of liver, lung, heart, spleen, kidney, and ovary of either the homologous species or the heterologous species tested. The alcoholic extracts of brain and testicle cannot be distinguished serologically. The alcoholic extract of testicle is iso-antigenic when activated with a foreign protein.
The Potency and Changes with Storage of Poliomyelitis Serum
Authors: Brodie Maurice
Published: January 2023

Summary and Conclusions

Pooled specimens of poliomyelitis convalescent serum vary considerably in potency, as would be expected since serums from convalescent donors vary in titer and some even fail to show any demonstrable antibodies. A rough test for each individual donor would be practical in the case of adults, either convalescent or so called “normals” (8) from whom considerable amounts of serum could be obtained.

Serum that has been preserved with 0.2 per cent phenol and kept on ice can be used clinically at the end of a year, for it has lost approximately only 20 per cent of its neutralizing power. At the end of the second year, however, it is only about one-half of the original strength. At the end of the fourth year, it is approximately one-quarter its original strength. This agrees with Burnet and MacNamara (9) who found that serum stored for three years still had neutralizing power.

With the use of a standard technic such as that used in the above work, it is possible to compare the strength of other poliomyelitis serums with that of human convalescent serum.

The present work indicates that human poliomyelitis convalescent serum is highly viricidal in vitro, for as little as 0.04 cc. neutralized 80 paralyzing doses of virus. However, this does not indicate that the virus can be neutralized in vivo, as it is probably fixed to the neurones (10) and cannot be destroyed by the serum.
Absorption of Tetanus Toxin by Brain Tissue of Animals of Various Ages
Authors: Beebe Agnes R.
Published: January 2023

Summary and Conclusions

A definitely diminished capacity to remove tetanus toxin from solution in vitro was demonstrated for the brain tissue of the very young rabbit as compared with the adult animal. Only a suggestive difference was found to exist between young and old guinea pigs in the ability of the brain tissue to absorb tetanus toxin. Newly-born rabbits were not found to possess a higher resistance to lethal doses of tetanus toxin than four- to six-week-old rabbits. The significance of the indifference of the young rabbit brain tissue to tetanus toxin is discussed, and possible explanations for the dissimilarity in behavior manifested by the young rabbit as contrasted with the young guinea pig are offered.
Hemolytic Streptococcus Toxins and Antitoxins
Authors: Malcolm Wilbur G. , Wyman Louise
Published: January 2023

Veldee stated that the use of a toxin prepared from the NY-5 strain of the hemolytic streptococcus in his rabbit ear method of testing was preferable to the use of toxins from other sources for determining the neutralizing value of antitoxins for therapeutic use. We have followed this suggestion for some time, employing a NY-5 toxin for test purposes and also for the production of antitoxin in horses. In May, 1932 we discovered that, although our antitoxin gave satisfactory neutralization values when tested against our own toxin, it failed to do so on titration with standard toxin obtained from the National Institute of Health. This was decidedly at variance with our earlier experience, for previously our antitoxins had neutralized both our own and National Institute toxins equally well.

This finding led us to obtain transplants of the NY-5 strains from the National Institute of Health and from the Bureau of Laboratories of the New York State Department of Health.
Susceptibility to Pneumococcus Infection as Measured by Species-Specific Agglutinins
Authors: Curphey Theodore J. , Ferrante Nancy
Published: January 2023

The variations in host response to controlled experimental infections have always offered a problem worthy of detailed investigation. The need for such investigation becomes increasingly important when such experimental infections form the basis for estimating the therapeutic efficiency of various antisera used in the treatment of specific bacterial infections. Thus in the course of studies on pneumococcus infection in rabbits after the method of Zinsser (1) and Goodner (2) it soon became apparent that the susceptibility of animals when measured by such factors as the size of the local lesion and the degree of blood stream invasion, varied within extremely wide limits, following upon injection of a relatively constant intradermal dose of virulent type I pneumococci. It was felt that a more detailed study of these experimental infections might throw some light on the question of host susceptibility.
A Ring Precipitin Test for Estimating the Concentration of Antibody in Small Amounts of Immune Serum
Authors: Hanks John H.
Published: January 2023

Summary and Conclusions

A ring precipitin method has been described for estimating the concentration of antibody in small amounts (0.03 to 0.21 cc. is sufficient for a preliminary titration and for duplicate checks) of immune serum. The test depends on allowing an optimal amount of antigen to diffuse into increasing dilutions of the antiserum in such a way that the smallest detectable concentration of antibody is precipitated in the form of a visible ring on the upper surface of the gelatinized antigen.

Data are presented on the control of variables and on the quantitative aspects of the procedure in the titration of anti-horse serum, as checked by the “optimal proportions” method of Dean and Webb. Preliminary information on the titration of other antigen-antibody systems has been given.
The Antigenic Action of the Phosphatides
Authors: Wadsworth Augustus , Maltaner Elizabeth , Maltaner Frank
Published: January 2023

With highly purified preparations of cephalin and lecithin, no antigenic action was demonstrable in our previous studies (1). When rabbits were injected with these phosphatides, alone or in combination with swine serum, the sera thus obtained failed to react specifically with either of them in complement fixation tests. Neither cephalin nor lecithin fixed complement in the presence of syphilitic serum. The advantage of a precise serological method of differentiating nonspecific and specific complement fixation was demonstrated, since, by its use, reactions which occurred and might otherwise have been regarded as significant were classified as nonspecific.

In earlier studies (2, 3, 4), marked differences in the chemical and physiologic activity of these purified phosphatides were observed, which may be correlated with differences in their structure. Lecithin has an anhydride structure and in benzine or ether-alcohol solution is neutral, whereas cephalin is a monobasic acid and has a definite neutralization value.
Some Observations on the Question of the Various Manifestations of Antibody Activity Being Due to Separate Antibodies or an Immune Substance Acting Differently Under Various Conditions
Authors: Teale F. H.
Published: January 2023

In this paper are recorded experiments bearing on the question of the different aspects in antibody activity being due to the action of a single immune substance or due to various types of antibody. The experiments deal with the problem by: (a) the study of the development of the various types of antibody activity, and (b) the study of differential adsorptions and differential temperature destructions.

Teale and Embleton (1913) showed that the lytic antibody passed through various stages during the course of its development before it became thermostable, viz., in the earliest stages it appeared as a type of specifically differentiated complement, then as a thermolabile immune substance activated by the non-specific complement and finally as the usually recognised thermostable antibody. In this paper these observations will be confirmed and extended and in addition it will be shown that although the lysins pass through phases mentioned, the agglutinin and protective properties are thermostable from commencement of their formation.
The Rôle of the Precipitin Antibody in the Removal of Intravenously Injected Antigen
Authors: Culbertson James T.
Published: January 2023

The antibodies which arise naturally following exposure to a disease agent or are provoked experimentally by the introduction of a suitable antigenic material, are said to be an evidence of the immunity which an animal possesses against the antigen. Some workers believe that the antibody is merely an adventitious accompaniment of the immune state of the animal without being essentially related to overcoming or removing the foreign agent and its effects. Others, on the contrary, feel that the antibody is an important functional part of the protective mechanism of the animal, and is instrumental in preventing injury to the animal body.

In order to throw some light on this question numerous workers have reported studies in which the time needed by a specifically immunized animal was compared with that required by a normal animal for the disposal of a test injection of antigen. Horse serum has been used as the antigen in many of these investigations.
An Immunological Study of the Effects of Intense Sound Vibrations on Egg Albumin
Authors: Flosdorf Earl W. , Chambers Leslie A.
Published: January 2023

The coagulum produced by sonic radiation of egg albumin solution has a much decreased antigenic activity and an altered specificity. The altered specificity of the coagulum is similar to the specificity of albumin denatured in other ways. The soluble fraction remaining after sonic radiation is unaltered immunologically. Prolonged radiation increases the amount of coagulum produced and then redisperses it into an opalescent sol of the same altered serological specificity. Very prolonged radiation decreases the amounts of both serologically native and altered proteins. Excellent agreement, both with respect to antigenic activity and specificity, was observed in the results with the Arthus phenomenon, the intradermal tests and in the precipitin reactions. In some cases the intradermal test was somewhat more delicate than the precipitin reaction.
The Flaring up of Injection Sites in Allergic Guinea Pigs
Authors: Dienes L. , Simon F. A.
Published: January 2023

In guinea pigs injected intracutaneously with human serum or turtle egg, a flare-up of the injection site can often be observed after an interval of a few days. This occurs at the time when skin sensitiveness begins to develop usually on the fourth to sixth day. Both the flare at the original site and the skin test at this time are purely of the delayed type and anaphylactic shock cannot be produced in the guinea pigs.

In the reacting flare about the original site of inoculation the tissues show infiltration with mononuclear cells which is characteristic also of the delayed type of skin reaction. It is pointed out that the developing allergy probably plays a rôle in the development of specific tissue reactions in the lesions of certain infectious diseases.
The Antigenic Action of Cholesterol
Authors: Wadsworth Augustus , Maltaner Elizabeth , Maltaner Frank
Published: January 2023

From seven of the ten rabbits inoculated with mixtures of cholesterol and swine serum, antisera were obtained which reacted to a definite degree with a suspension of cholesterol as antigen in the usual form of complement-fixation test.

With special methods of comparative titration, these reactions differed from those of known specificity on the one hand and, on the other, appeared similar to the nonspecific reactions of normal serum. In the reactions of known specificity which have been studied, the amount of complement fixed was directly proportional to the amount of immune serum used, whereas, in the reaction of cholesterol and cholesterol antisera, it was not directly proportional—quite the contrary. Furthermore, reactions of known specificity were not appreciably affected when the concentration of serum constituents in the dilutions of serum tested was maintained constant by the use of normal serum instead of physiological salt solution as diluent, whereas, under similar conditions, the reactions with cholesterol that were observed when dilutions were made with salt solution did not develop when normal serum was substituted.
Studies on the Venoms of North American Pit Vipers
Authors: Githens Thomas S.
Published: January 2023

This study of the venoms of North American pit vipers brings out the following points: The amount of venom secreted by each species varies directly with the size of the species.There are great differences in the toxicity of venoms from closely related species.The more primitive forms have venoms more toxic to the nerve centers.Species secreting a small amount of venom tend to have more active venoms, while those yielding large amounts have weaker venoms, so that the number of fatal doses in one extraction is more constant than are other factors.The larger species of viper give the largest number of fatal doses per extraction.The danger to man from the bites of pit vipers, varies almost directly with the size of the species.
Hemorrhagic Reaction at the Site of Injection of Toxins After Intravenous Injection of Starch in Young and Adult Rabbits
Authors: Freund Jules , Hosmer Elizabeth Page
Published: January 2023

When certain bacteria or their products are injected into the skin of rabbits and on the following day the same material is injected into the blood stream, hemorrhage or hemorrhagic necrosis results in the skin at the site of the first injection (Shwartzman (1), Hanger (2)). The nature of this reaction, called the Shwartzman phenomenon, is not understood.

It seems to be significant from the point of view of the mechanism of the reaction that Sickles (3) was able to show that the bacterial toxins of the second (intravenous) injection can be replaced by a suspension of agar. Shwartzman (4) found that when a mixture of precipitinogen and serum containing homologous precipitin is injected into a vein hemorrhage follows in the skin in an area prepared by bacterial filtrates. It was reported recently (5) that the introduction of 10 cc. of a 10 per cent starch solution into the blood stream causes hemorrhage in the skin at the site of injection of bacterial filtrates or eelserum.
Studies of Anaphylaxis in the Albino Rat with Reference to Diet and Histamine
Authors: Pratt Henry N.
Published: January 2023

Summary and Conclusions

In 42 albino rats sensitized to horse serum or egg albumen by large multiple doses, only 2 failed to show some observable signs or pathological changes of anaphylactic shock. However, the individual variation in susceptibility was great. In general, shock was clinically more striking in small or malnourished rats, while in adults the in vivo signs might be entirely lacking and yet the pathological changes be typical. A bread diet did not increase the susceptibility to shock. The pathological changes of anaphylactic shock in the rat consist of venous congestion, edema, hemorrhage, and eosinophilia, being most extensive in the upper intestinal tract. In some instances at least, the typical pathology of experimental asthma was produced. Specific Dale uterine reactions could not be obtained, although occasional non-specific contractions were noted. Histamine in a dilution of 1:7500 caused a good, sustained contraction of the excised uterus, whereas a dilution of 1:1,000,000 produced relaxation of tone and inhibition of rhythmicity as reported by others. Rats uniformly produce precipitins when large, multiple doses of horse serum or egg albumen are administered. The measurable weight of the rat's adrenal gland is unaffected by shock or bread diet.
An Immunological Study in Laboratory Animals of Thirteen Different Strains of Equine Encephalomyelitic Virus
Authors: Howitt Beatrice F.
Published: January 2023

Eleven strains of equine encephalomyelitic virus isolated from different localities of the United States could be divided serologically into 2 groups, one from the West (California, Nevada, Utah (Nos. 1 and 5), Colorado, South Dakota and Minnesota) and one from the East (New Jersey (Nos. 1, 2 and 3), Maryland (Md. 1) and Delaware). The strain of virus obtained from the Argentine was classified with the western series, while that from Russia was immunologically distinct from the others and varied in a few characteristics. There was no in vitro cross neutralization nor in vivo cross protection between serums of any group when tested against the heterologous viruses. Protection occurred, however, between homologous serums and viruses of each type. Animals immunized to each member of the 3 divisions showed a constant tissue immunity within their own groups when tested intracerebrally, but cross injection experiments were not conclusive, except for the Russian virus which was differentiated from the others. A certain percentage of guinea pigs immune to the western American strains showed immunity when tested with the eastern and vice versa. The numbers of animals succumbing or surviving after injection with heterologous strains was approximately proportional for both eastern and western American varieties. Young guinea pigs born of immune parents and immune to their respective American viruses were more susceptible to injections of the heterologous strains than older animals hyperimmunized with massive doses of live virus. The American eastern strains of virus were found to be far more invasive and potent than the western, both by intracerebral and by intradermal inoculation of guinea pigs, although the virulence of both could be enhanced by repeated animal passage. Rabbits were found to be more susceptible to the eastern american strains than to any of the others and could even be infected intravenously. The Russian virus was also invasive for rabbits when given intracerebrally but not when into the veins. Comparison of potency was best demonstrated by titration methods. Although 3 serological groups of equine encephalomyelitic virus may be differentiated, there is a probability that the strains isolated from horses in the various localities have sprung from a common root stock and should therefore be considered as varieties or subvarieties of the identical virus causing the same clinical disease.
Blood Grouping of Rwala Bedouin
Authors: Shanklin William M.
Published: January 2023

The racial purity and antiquity of these Arabs is deduced from the high percentage of group O in the 320 Rwala Arabs examined. The results of this examination seem to indicate that the Rwala are in some way related to the American Indians on account of the close resemblance between their blood-typings, while it would appear that no such relation exists between them and the other Asiatic races previously typed. It is suggested that both the Rwala and the American Indians separated from the rest of the human race before the appearance of factors A and B.
Purification of Diphtheria Toxin and Anatoxin
Authors: Ando K. , Komiyama T.
Published: January 2023

Summary and Conclusions

Calcium-phosphate formed at a certain range of pH absorbs diphtheria toxin or anatoxin. The largest percentage yield was obtained between pH 5.3 and 6.0 for the toxin used and between pH 5.6 and 6.3 for the anatoxin studied, whereas the purest product was obtained between 6.7 and 6.9 for the toxin and in pH 5.3 for the anatoxin so far as the Lf-unit was concerned. For this purpose the use of H3PO4 and NaOH were found convenient. By combining this method and the ZnCl2 method (Hosoya) it was possible to obtain anatoxin of high purity. Anatoxins purified by these methods, after the addition of 0.5 per cent phenol, were found quite stable in storage at room temperature or in the cold. Animal experiments with these purified anatoxins showed the same degree of antigenicity as that of the original anatoxin irrespective of their degree of purification, but in accordance with their Lf-units. The anatoxin purified by the ZnCl2 method often showed no flocculation, as pointed out by Hosoya, yet its Lf-units could be determined by the blending method so that it is no exception to Ramon's conception that the antigenicity of anatoxin could be determined by the Lf-unit in vitro-test. Contrary to the finding by Schmidt and Kjaer that the anatoxin purified by acid was less antigenic than that expected from its Lf-units, the antigenicity of the acid-purified anatoxin was found by the animal test to correlate with its Lf-units in vitro-test. Highly purified anatoxins were compared with their original anatoxins by the Moloney test and it was found that the big difference in the N-content finds no expression in that test.
Limited Observations on the Antistreptolysin Titer in Relation to Latitude
Authors: Coburn Alvin F. , Pauli Ruth H.
Published: January 2023

From the data presented in this paper it is seen that the median antistreptolysin value is lower in latitudes south of 35° than in latitudes north of 40°.

This method of study is suitable for detecting an environment in which the rheumatic subject may expect minimal exposure to hemolytic streptococcus infection of the respiratory tract.
On Von Dungern's Indigo Test for Syphilis
Authors: Fujimoto B.
Published: January 2023

Von Dungern's indigo test for syphilis is practically unavailable for the serum diagnosis of syphilis, because we can not find any difference as to this test between syphilitic and nonsyphilitic sera. Among the substances that the reagent contains neither indigo nor salts play any part in the inhibition of the coagulation, as von Dungern formerly thought. The coagulation of sera in this reaction is prevented only by the alkali, as Flood proved. The degree of alkalinity that can prevent the coagulation of serum, varies according to the individual, not according to the presence or absence of syphilis. On the other hand, the alkalinity that prevents the coagulation of sera varies according to the concentration of the sera; that is, the more diluted the serum, the more easily may its heat coagulation be prevented by alkali.
Studies on the Antitrypsin of Serum
Authors: Fujimoto B.
Published: January 2023

Introduction. As to the nature of the antitrypsin of serum, a great deal has been written, and even at the present day various views are held in regard to it. In our laboratory several tests were performed in order to see how it can be inactivated and which part of the serum exerts the antitryptic action.

Preparation and Method of Our Tests. In our experiments von Bergmann's casein method was modified a little to make the reaction finer. Namely: Solution of casein: 0.5 gram of casein was dissolved in 50 cc. of N/10 NaOH solution and the solution was warmed a while. Then the solution was neutralized with N/10 muriatic acid and finally diluted to 500 cc. with normal salt solution. This solution of casein in our case is, therefore, less concentrated than that usually employed; i.e., it is of 0.1 per cent instead of 0.2 per cent.
The Influence of Active Normal Serum (Complement) upon Meningococci
Authors: Kolmer John A. , Toyama Ikuzo , Matsunami Toitsu
Published: January 2023

Introduction It is generally true that the antibacterial properties of both normal and immune sera are greater when perfectly fresh than after being heated or allowed to stand for weeks or months with the addition of a preservative as shown in chart 7 with the opsonins in antimeningitis serum. This is probably due not only to deterioration of specific antibodies in immune serum but also to the loss of certain labile substances in normal and immune sera alike and particularly those substances generally designated as complements and normal opsonins. Antibacterial sera are especially likely to show differences in activity in their fresh state as compared with the same sera after being heated or after standing, and particularly when examined by test tube methods, whereas the antitoxic sera are usually more stabile; these differences in the case of the antibacterial sera may be ascribed in part to the loss of the labile complementary substances regarded as essential or important in the mechanism of their antibacterial activity.
The Influence of Active Normal Serum (Complement) upon Meningococci
Authors: Matsunami Toitsu , Kolmer John A.
Published: January 2023

The bactericidal activity in vitro of different antimeningitis sera was found to be quite low. Fresh or active antimeningitis sera was somewhat more bactericidal than the same sera after inactivation by heating at 60°C. for thirty minutes. Active normal human and guinea-pig sera are generally slightly bactericidal for meningococci. The bactericidal activity of horse-antimeningitis and normal human and guinea-pig serum, is largely independent of complemental bacteriolysis. The bactericidal activity in vitro of normal and immune sera was best shown by a pipet method employing small numbers of cocci and relatively large volumes of serum. The addition of active normal human and guinea-pig serum to antimeningitis serum sometimes increased the bactericidal activity of the latter. Whole human and guinea-pig blood was found slightly more bactericidal than the sera alone. Normal human and guinea-pig sera frequently agglutinates meningococci in final dilutions up to 1:4, but not in higher dilutions. Antimeningitis sera containing the largest amounts of agglutinin were found to possess most opsonin and apt to prove most bactericidal in vitro. The mouse test of Hitchens and Robinson was found under certain technical conditions to be of value as a means for determining and measuring approximately the protective and curative value of antimeningitis serum. Normal active human and guinea-pig sera were practically without demonstrable protective value in mice infected with virulent meningococci, although the addition of these normal sera to antimeningitis serum appeared in some experiments to slightly increase the protective power of the latter. The addition of active normal human or guinea-pig serum (complement) to antimeningitis serum cannot be expected on the basis of our experiments, to greatly augment bactericidal activity because complemental bacteriolysis exerts but a minor rôle in the relatively feeble bactericidal activity of antimeningitis serum, but the addition of normal sera definitely increases opsonic activity (10) and since it would appear that a large part of the curative properties of antimeningitis serum is to be ascribed to the presence of opsonin, it is suggested as worthy of clinical trial to complement the antimeningitis serum by the addition of active human or guinea-pig serum prior to intraspinal injection and particularly in the treatment of severe and serum-resistant infections.

For this purpose human serum is superior to guinea-pig serum and may be obtained from the patient or a volunteer with the usual precautions for asepsis.
The Study of Problems of Immunity by the Tissue Culture Method
Authors: Burrows Montrose T. , Suzuki Yoshio
Published: January 2023

In a previous paper Suzuki (1) has shown the value of the tissue culture as a means for a more detailed study of the nature of the conditions of natural immunity in animals. The present paper describes other experiments outlined for the purpose of studying more carefully the general distribution and action of antitoxic substances. It has been shown by Suzuki that chickens' tissues are sensitive in the tissue culture to the action of diphtheria toxin when this is added to the medium. Antitoxin when injected into chickens protects the chickens against lethal doses of toxin. The distribution of the antitoxin within these animals became of interest for analysis. Again, it seemed evident that the tissue culture method would be of use for the quantitative standardization of toxins. It thus became of interest to test the neutralizing power of antitoxin for toxin by this method.
The Influence of Arsphenamine and Mercuric Chlorid Upon Complement and Antibody Production
Authors: Toyama Ikuzo , Kolmer John A.
Published: January 2023

Numerous studies indicate that several drugs and particularly arsenic compounds, may stimulate antibody production and that their curative effect in the treatment of disease and particularly syphilis and experimental trypanosomiasis, may be ascribed to this influence upon antibody production in addition to their direct parasiticidal influence. In our experiments, the intravenous administration of arsphenamine to normal rabbits in doses varying from 0.01 gram to 0.004 gram per kilogram of body weight (equivalent to 0.6 to 0.24 gram per 60 kilos), did not result in an increased output of immune hemolysin to sheep cells, but rather suppressed hemolysin production; smaller doses did not appear to retard hemolysin production to sheep's and human cells but likewise they did not result in an increase. The smaller doses, however, generally produced a slight increase of agglutinin for sheep's and human cells. Similar results were observed with mercuric chloride; large doses appeared to suppress hemolysin and agglutinin production while smaller doses tended to increase the production of hemagglutinins but not that of the hemolysins. A single large dose of arsphenamine (0.06 gram per kilo) administered intravenously to rabbits reduced the hemolytic activity of their sera within a period of twenty-four hours after injection, probably by an influence upon the hemolytic complement; the administration of a smaller dose (0.6 gram) to syphilitic persons as part of the treatment of their infection, was found generally to produce a depression in the hemolytic activity of the serum as tested one hour after injection followed by a general increase within eighteen hours. Large doses of arsphenamine and mercuric chlorid to rabbits tended to limit agglutinin production for typhoid bacilli; single doses of arsphenamine (0.6 gram) in adults did not influence the amount of normal typhoid agglutinin in their sera. The general result of these experiments indicates that while massive doses of arsphenamine and mercuric chlorid tend to suppress antibody production and cause a decrease in hemolytic complement, smaller doses tend to increase the production of antibody (agglutinins) and augment the complement content after a primary decrease. It is probable that both drugs administered in the treatment of syphilis, owe part of their therapeutic efficacy to their influence upon increasing antibody production and complement.3
A Contribution to the Study of the Complement Fixation Reaction in Tuberculosis
Authors: Wilson M. A.
Published: January 2023

I. On the Standardization of Complement. In our study of complement fixation in tuberculosis we have found a point of technique that has increased the efficiency of the test. It has to do with the standardization of the guineapig's serum to determine the value of the complement. In this preliminary report, we shall descn'be the method or standardizing the complement, the preparation of our tuberculosis antigen,and the diagnostic test, with such results as we have obtained thus far in our study.

Technique. All reagents are used in one tenth the classic Wassermann volumes. Fixation period, one hour, 37°C.

Serum. The patient's serum is inactivated for thirty minutes at 56°C. 0.02 cc. and 0.01 cc. of the undiluted serum are used in the test, and 0.04 cc. for control of anticomplementary action.

Antigen. Two antigens have been used. One was made from 12 stock cultures of human tubercle bacilli, the other from strain 305 (used for tuberculin production.)
On the Mode of Action in Vitro and the Preparation of Hemolytic Antibodies
Authors: Balls A. K. , Korns John H.
Published: January 2023

In vitro, as hemolysis proceeds, the total amount of amboceptor is constant but the stroma of the laked red cells increasing in amount, they become less and less saturated with amboceptor, and so split off less of it by dissociation, thus causing the velocity of hemolysis to decrease. In vivo the stroma produce specific hemolytic and agglutinative bodies of high titer. Since little protein is injected the toxicity seems to be nil. Alcohol and ether extracts, as well as 0.85 and 5 per cent salt solution extracts, of the stroma do not bind amboceptor in vitro. The extract of stroma with alkaline physiological salt solution, as described above, does bind amboceptor in vitro and on injection causes the development of specific hemolysins but not of agglutinins. This alkaline extract contains nucleo-protein, but not simple albumin or globulin. It also contains lipoids but these probably are not essential to its antigenic function. The presence or absence of the anaphylactic reaction is not a certain criterion for specificity when nucleo-protei nsare used as antigens. In our work, hemolysins, showing species specificity, were present in the absence of anaphylaxis.
The Mass Factor in Immunological Studies Upon Viruses
Authors: Merrill Malcolm H.
Published: January 2023

A study has been made of the relationship between size of antigenic particles and the number of particles necessary to produce visible immunological reactions. This mass-number relationship has been shown graphically. It has been suggested that the reason immunological reactions have not been obtained with viruses in vitro is that insufficient concentrations of virus particles have been used. The importance of considering antigenic mass in studies upon immunization with viruses and in immune body absorption experiments has been emphasized.
Quantitative Studies on the Neutralization of Equine Encephalomyelitis Virus by Immune Serum
Authors: Merrill Malcolm H.
Published: January 2023

Summary and Conclusions

When equine encephalomyelitis virus and a subneutralizing dose of immune serum were mixed and then diluted the titer by intracerebral inoculation was from 10 to 100 times below the titer of the same materials mixed after dilution. When virus was inactivated by mixing with immune serum all dilutions of the mixture were noninfective upon intraperitoneal inoculation. When each was diluted before mixing, animals receiving the higher dilutions were not protected. The filterability of the virus was diminished by mixing with subneutralizing doses of immune serum. It is concluded from these results that the virus and immune body combined in vitro. It is considered probable that aggregation of the virus particles occurred.
Observations on Poison IVY Hypersensitiveness in Guinea Pigs
Authors: Simon Frank A.
Published: January 2023

A dietary deficiency in vitamine C inhibited the development of hypersensitiveness to poison ivy in guinea pigs.

A well developed hypersensitiveness was demonstrated 7 days after the first application of the extract.

Injection of the extract intramuscularly, intraperitoneally, and intravenously did not result in hypersensitiveness or did so to a slight degree only, whereas application to the skin surface resulted in a definite hypersensitiveness.

Sensitization of tissues other than the epidermis was not demonstrated.

Passive transfer with the serum could not be demonstrated.

Excision of the area of skin to which a sensitizing application had been made was ineffective in preventing the development of hypersensitiveness provided such removal was made from 18 to 24 hours or longer after application. Excision of the site before this time prevented the development of sensitization.

The method of spread of hypersensitiveness from the site of application of the extract over the general body surface was investigated but positive evidence was not obtained.

Histological study of the lesions revealed evidence of an acute inflammatory reaction in both epidermis and papillary layer of the corium, with considerable necrosis of epidermal cells. This reaction was observed in both a sensitized and a non-sensitized guinea pig but was definitely more marked in the former than in the latter.

Attempts to sensitize the rat, rabbit, and cat to poison ivy were unsuccessful.
Antigenic Properties of Brain Tumors
Authors: Weil Arthur , Liebert Erich
Published: January 2023

Summary and Conclusions

Following intraperitoneal injections into guinea pigs and intravenous injections into white rabbits, saline emulsions of gliomas and brain tissue in combination with dog serum as a carrier stimulated the production of specific antibodies. A higher titer of the antiserum was obtained following intravenous injections into white rabbits of alcoholic extracts of formalin fixed brains and gliomas. Alcoholic extracts of meningiomas did not stimulate the production of specific antibodies.

The serum of a patient with glioblastoma multiforme contained antibodies against glioblastoma together with antibodies against human brain.
Antileucocytic Serum
Authors: Chew W. B. , Stephens D. J. , Lawrence John S.
Published: January 2023

A method was described for the production of an antileucocytic serum relatively free of hemolytic antibodies.

The parenteral injection of this antiserum into guinea pigs was shown to depress the number of neutrophils in the circulating blood with less effect upon the lymphocytes. The monocytes, eosinophils and basophils reacted much as they did to similar injections of normal rabbit serum. The numbers of platelets and red cells were not significantly altered.

Following intracardial injections of the antiserum the neutrophils disappeared from the blood within 5 minutes and since large numbers of them could not be found in the tissues at this time it is evident that they very rapidly disintegrated beyond the stage of morphological recognition upon contact with the antibody.

Following intraäbdominal injections of the antiserum the characteristic disappearance of neutrophils occurred within one to 7 hours and persisted to between 24 and 48 hours. In 72 to 96 hours the neutrophils returned to normal or to somewhat increased numbers.

When injections were repeated a tolerance developed so that an equal dose caused less effect. It was shown that this tolerance was probably not due to antibodies developed against the proteins of rabbit serum or against the leucotoxic antibodies themselves.

A striking degree of myeloid hyperplasia was present in the bone-marrow of repeatedly injected animals, as well as a moderate degree of lymphoid and endothelial hyperplasia in the lymphnodes and spleen.

There was no constant evidence of damage to other body-cells with the amount of antiserum used.

It was possible to prolong the period of neutropenia to 4 or 5 days by daily injections of increasing amounts of antiserum without seriously affecting the general condition of the animals. It is probable that the period could have been further prolonged by properly increasing the amounts of antiserum injected. It was shown that neutrophils were not available for local tissue-reactions to the subcutaneous injection of virulent staphylococci or to the intraäbdominal injection of a beef broth-gum acacia mixture in animals rendered neutropenic by an injection of the antiserum.
Variation in the Susceptibility of Guinea Pigs to Reversed Passive Anaphylaxis
Authors: Zinsser Hans , Enders John F.
Published: January 2023

For some time the writers have been interested in the reactions which may take place when preliminary injections of antigen are followed in the same animal by administrations of homologous antiserum, a class of phenomena spoken of as “reversed anaphylaxis.” Such reatcions have been described by Opie (1) in connection with the Arthus phenomenon and have been recently observed, with general reactions, in guinea pigs by Kellett (2, 3). We have long been interested in experiments designed to determine whether the supposed union of antibody with sensitized cells, in passive sensitization, implied the actual attachment of foreign globulin (the antibody-carrying protein) to the cells of the sensitized animals. These experiments have not yet been concluded, but in the course of our studies an observation has been made which strongly suggests fundamental hereditary differences between guinea pigs of different strains in their responses to in vivo reactions of antigen and antibody.
The Flocculation Reaction with Purified Diphtheria Toxin
Authors: Eaton Monroe D.
Published: January 2023

In diphtheria toxins purified by a considerable variety of methods, the number of m.l.d. per Lf unit generally falls between 20 and 40 provided the toxin has not been altered by the purification process used.

The Kf of toxin is a definite exponential function of the Lf concentration: Kf = k/Lf1.2 where (k) is a constant characteristic of the toxin and antitoxin tested.

Concentrated bacterial protein may modify or obscure the flocculation reaction.

The increase in Kf produced by acid, alkali and acetone, appears to be associated with denaturation of the toxic protein. This change is not the same as modification of toxin to toxoid.
Active Immunization against Poliomyelitis. A Comparative Study
Authors: Kramer S. D.
Published: January 2023

Of the 12 animals inoculated intra- and subcutaneously with the neutralized mixtures containing the equivalent of 1.5 grams of poliomyelitis cord, 10 survived sufficiently long to permit of neutralization tests. The serums of only 2 of the 10 animals contained sufficient neutralizing substance to protect the test animals. Of the 8 surviving animals 3 withstood the same dose of virus administered intracerebrally and likewise resisted the 0.1 and 0.2 cc. doses. Two of the 3 animals resisted the 0.4 cc. dose and one resisted the 0.8 cc. or 16 times the minimal constant infective dose.

Each of the 11 additional animals received four 5 cc. doses of the neutralized mixtures at weekly intervals, each dose containing the equivalent of 0.5 gram of poliomyelitis cord (total of 2 grams). Seven of the 11 animals possessed sufficient neutralizing substance to neutralize the 0.05 cc. dose of virus. Nine of the 11 animals withstood 0.01, 0.025, and 0.05 cc. of the virus intracerebrally. Five of the 8 survivors (one animal having died of dysentery) survived 0.1 cc. of virus. Three resisted 0.2 cc. (2 of the 5 died of intercurrent infections), and 2 of the 3 resisted 0.4 or 8 minimal constant infective doses of virus.

The neutralized mixture proved non-infective both on subcutaneous and intracerebral inoculation.
Serum-Sickness in Rabbits
Authors: Jones Lloyd , Fleisher Moyer S.
Published: January 2023

The studies here reported relate primarily to the rôle that the lipids play in the causation of serum-sickness in rabbits. The word lipid is used as an inclusive term embracing all those substances removed from serum by commonly employed solvents such as alcohol, ether and similar materials. We have previously been led to the conclusion that while the pseudoglobulin of horse-serum is the most important of the 3 major serum proteins in causing serum-sickness in rabbits (1), it seems probable that it is not the pseudoglobulin as such which is the factor responsible for the occurrence of the disease. Our attention was therefore directed towards the possible significance of serum-lipid in causation of serum-sickness. We have therefore exposed whole horse-serum or horse-serum pseudoglobulin to various treatments with several commonly used lipid-solvents and have injected such sera into rabbits in order to determine the occurrence of serum-sickness.