bluuebunny/crossref_metadata_2025 huggingface dataset:
An Agglutination Reaction Observed with Some Human Bloods, Chiefly Among Negroes
Authors: Landsteiner K. , Strutton W. R. , Chase M. W.
Published: January 2023

In an attempt to produce immune sera for the human blood property (1) designated as P two batches of 12 rabbits each were injected with the blood of individuals known to give strong reactions for P. The first batch received blood of the type O, M, N of a white man L. F., the second that of a Negro C. H. (O, N), the latter having been used for the preparation of anti-P-serum once before. The animals received several courses of six daily injections of 0.1 to 0.4 cc. washed blood cells in a volume of 1 cc. The courses were separated by rest periods of eight days; a fourth course of injections was given ten weeks after the third. From the first lot of rabbits, after three courses of injections, one P serum of moderate strength and two rather weak sera were obtained.
Rate of Response of Rabbits to Two Antigens of Tubercle Bacilli
Authors: Reed G. B. , Rice Christine E. , Gardiner B. G.
Published: January 2023

In two recent papers (Rice (9); Rice and Reed (10)) it has been shown that colony variation in the acid-fast group of bacteria, in common with that in other species, is accompanied by variation in antigenic content.

These conclusions were based upon a study of the antibody content of the sera of rabbits subjected to a rather long course of immunization with heat-killed S and R types of tubercle bacilli or other acid-fast species. The experimental procedure consisted in determining the amount of complement fixed by the sera in the presence of, first an S antigen prepared from S organisms and secondarily in the presence of an R antigen by the quantitative complement fixation technique of Wadsworth, Maltaner and Maltaner (14). As a control pooled normal rabbit serum was tested with the same antigens. In each case the small value of this non-specific fixation of complement was subtracted from the fixation with the immune serum and the result styled the specific fixation.
Hemolytic Streptococcus Toxins and Antitoxins
Authors: Malcolm Wilbur G. , Wyman Louise
Published: January 2023

Identical mixtures of scarlet fever streptococcus toxin and antitoxin have been injected subcutaneously in the ear and intracutaneously in the body of rabbits selected as reactive to this toxin.

The reactivity of the two injection sites is the same for such mixtures. The larger area made available by the use of the body skin may, therefore, be expected to yield results comparable with those obtained by Veldee's method.

For titration of toxins and the residual in formalinized toxins, the ear reactions have proved easier to evaluate than skin reactions.
The Photodynamic Effect of Methylene Blue on Tetanus Toxin
Authors: Lippert Karl M.
Published: January 2023

The toxic properties of tetanus toxin in a filtered broth culture of C. tetani are rapidly diminished by the photodynamic action of methylene blue in certain concentrations. The inactivation of tetanus toxin in the presence of dilute solutions of methylene blue is more marked after one hour exposure to light than when the mixture is exposed for shorter intervals of time. Antigenic property could not be demonstrated in tetanus toxin after partial destruction of its toxicity by exposure to light in the presence of dilute solutions of methylene blue. An optimum concentration of methylene blue for the inactivation of tetanus toxin by light is demonstrated. In the concentrations used, methylene blue does not inhibit the effect of tetanus toxin in vivo.
A Note on the Concentration and Purification of Antimeningococcus Serum
Authors: Murdick Philip P. , Cohen Sophia M.
Published: January 2023

Previous experiments demonstrated that the neutralizing potency of antimeningococcus serum, as shown by the phenomenon of local skin reactivity, is associated with the water-insoluble globulin as are the agglutinative and precipitative activities (1). This fraction was effectively separated from immune horse sera which differed in water-insoluble globulin content, when the sera were dialyzed, diluted with distilled water, and acidified to the point of maximum precipitation. A preliminary report of the results of further purification of the active fraction is now presented.

Three methods were applied: precipitation of the inert protein by zinc or aluminum chloride, isoelectric fractionation, and fractional solution in dilute sodium chloride. The first two procedures with the exception of certain modifications were similar to those used by Felton (2, 3) in the purification of the potent fraction of antipneumococcus serum.

Precipitation of inert protein with zinc chloride was carried out as follows: The isoelectrically precipitated globulin was dissolved in 1 per cent sodium chloride and the reaction was adjusted to pH 7.6.
Factors Influencing the Speed of Flocculation
Authors: Ando K. , Komiyama T.
Published: January 2023

The higher the Lf-units of diphtheria-toxin or anatoxin, the smaller the Kf-value, as has been asserted by many observers. If diphtheria toxin or anatoxin is freed from accompanying substances by dialysis or purification by the calcium-phosphate method, its Kf-value becomes smaller. The Kf-value of diphtheria-toxin or anatoxin largely depends on its pH. Irrespective of the kind of culture media in which toxin was produced, it was found that (a) the Kf of the purified and its original toxin is least in the untreated solution and increases with the amount of acid or alkali added. (b) When purified toxin was mixed with buffer solutions of different pH, the Kf was found to be the smallest in the mixture with the buffer of pH 6. (c) Both original and purified anatoxin had the smallest Kf-value in the most acid range within which flocculation did occur. Anatoxin prepared from semi-synthetic broth toxin the Kf of which was found ∞, showed flocculation when it was dialysed, acidified or purified.
The Individual as a Factor in Antidiphtheria Immunity
Authors: Neill James M. , Sugg John Y. , Richardson Lurline V.
Published: January 2023

The experiments dealt with the influence of different methods of immunization upon the antitoxic response of groups of guinea pigs. The points investigated included the condition of the antigen, the total amount of antigen, the division and spacing of doses and the route of injection.

The adequacy of the different methods for group immunization was analyzed on the basis of the percentage of individuals made Schick negative. The total amount of antigen influenced the immunity response but to different extents in different zones of dosage: its influence was masked in the zone of “hyperimmunization,” but within the zone “adequate for group immunization” it was manifested in speed of response, and within the zone “inadequate for group immunization” both in speed of response and in percentage of a group finally made immune. However, the amount of antigen could be counterbalanced by other factors: to some extent by the route of injection but especially by the division and spacing of injections.

The results are discussed in terms of the expression: A = f(C × S) in which A represents antitoxin production, C, the capacity to respond to specific stimulus and S, the stimulus of the specific antigen. In the present paper this formula was used in the analysis of the development of immunity; in later papers it will be modified for the analysis of immunity possessed long after the last injection of antigen.
Incidence of Serological Types of Hemolytic Streptococci in Recent Cases of Erysipelas
Authors: Spicer Sophie , Gonshorek Mary F. , Spicer Emily L.
Published: January 2023

From 52 erysipelas cases sixteen strains of hemolytic streptococci of the beta type were isolated. Only two strains, a smooth and a coarse, obtained from the erysipelatous lesion of the same patient fell into one of our previously determined groups, that of type IV scarlet fever. Two other strains absorbed, one from each of 2 serums prepared with the new erysipelas strains. However, we cannot consider having found any new agglutinating groups, 2 not being considered sufficient to constitute a group. The antibacterial potency of 2 erysipelas serums, one prepared by the New York City Department of Health and one by the Lederle firm, proved to be of low value, as evidenced by protection tests on white mice. The Otisville erysipelas serum protected to a greater extent than the Lederle serum against the homologous strain, and both protected to about the same degree against the new erysipelas strains. An antiscarlatinal serum prepared at Otisville and intended to serve as control on type specificity in relation to protection, gave almost as much protection as the Otisville erysipelas serum, and more protection than the Lederle serum against one of the major strains used in their preparation, and better protection than either of the erysipelas serums against the new erysipelas strains. A rabbit serum prepared from one of the strains of the new erysipelas series, while being highly potent against its own strain (homologous strain), protected against the other new erysipelas strains to about the same degree as did the antiscarlatinal serum. It protected, however, against the major type erysipelas strain used in the preparation of both erysipelas horse serums to a greater extent than was its own strain protected by either of the erysipelas serums.
The Adaptation of a Staphylococcus Bacteriophage to an Artificially Produced Anti-Bacteriophagic Serum
Authors: D'Herelle F. , Rakieten M. L.
Published: January 2023

Several reports dealing with the influence of body fluids on staphylococcus bacteriophage have shown that human serum and pus markedly interfere with the in vitro lysis of staphylococci by bacteriophage (Gratia and Mutsaars, 1931; Applebaum and MacNeal, 1932; Colvin, 1933; Burky, 1933). It has been our experience that, while an inhibition of staphylococcus bacteriophage may be demonstrable, there are considerable differences in the action of several races of staphylococcus phages in the presence of the same concentrations of serum. It appears that this difference, the ability of a staphylococcus bacteriophage either to bring about lysis or to be rendered impotent in serum, is dependent upon the “quality” of the bacteriophage. With regard to this statement the observations of Bail (1923), Asheshov (1924); Morrison (1932); Pasricha (1932); Schlesinger (1932); and Burnet (1933) concerning the complex composition of bacteriophages, as they are employed in the laboratory, are extremely important.
The Relation of Heterophile Immunity to the Incidence of Colds
Authors: Rockwell George E. , Van Kirk Herman C.
Published: January 2023

This is a report of a more intensive study of 47 of the 1036 patients reported in a previous article (1). The 47 cases reported in this paper consisted of 30 cases who received the oral vaccine, and 17 cases who were used as controls. The object of this study was to show the relation between the patient's response to the heterophile antigen, and his frequency of colds. These cases were chosen because of the availability of blood samples. An effort was made to distribute the cases who had received the oral immunization between those who had apparently benefited and those who had not. The heterophile titer of the blood sera of the patients was then studied in relation to the distribution of colds in these groups.

The vaccine consisted of rough pneumococci (D.R.I.) and streptococci. The pneumococci were high in heterophile antigen. Each capsule contained one hundred billion of each organism.
Post-Anaphylactic State in Guinea Pigs
Authors: Ostromislensky I. , Openchowski M.
Published: January 2023

Sensitized guinea pigs which received on reinjection a sublethal dose of antigen and therefore survived the anaphylactic shock, are in a pathological state. As a rule, this characteristic post-anaphylactic state is easily discovered on the seventeenth day after the reinjection of the antigen. It is expressed in sharply changed reactions of animals to various chemical preparations, e.g., to azo-compounds, and in particular to chrysoidin (2.4-diaminoazobenzol). Subcutaneous injection of chrysoidin produces in these animals a peculiar reaction the symptoms of which greatly resemble those of acute anaphylactic shock in rabbits. In the post-anaphylctic state guinea pigs tolerate some chemical preparations, and in particular chrysoidin, in considerably smaller quantities than do normal animals. The post-anaphylactic state of guinea pigs changes into normal state by itself not later than thirty-one days after the shock. Timely injections of some anti-shock preparations prevent not only the anaphylactic shock, but likewise the post-anaphylactic state of guinea pigs. To these preparations belong: (a) phenylmethylpyrazolone; (b) phenyldimethylpyrazolone (antipyrine); (c) di-phenylmethylpyrazolonyl (Rossium); (d) the sodium salt of Phenyldimethylpyrazolonylaminomethylene sulphonic acid (melubrine); (e) methyloxindol; (f) alpha-phenyl-alpha-acetyl-hydrazine.
The Relationship of Circulating Antibody to the Local Inflammatory Reaction to Antigen (the Arthus Phenomenon)
Authors: Culbertson James T. , Kent John F.
Published: January 2023

The results shown in this paper indicate that the presence of circulating precipitin is necessary for local inflammatory reactions of the type described by Arthus. The severity of the Arthus reaction in the skin is directly correlated with the amount of antibody in the blood. When the circulating precipitin disappears with time or is eliminated by an intravenous injection of antigen from an actively sensitized animal known to be capable of giving an Arthus reaction, that animal is no longer sensitive to the skin test. The injection of an amount of antigen just sufficient to remove all the circulating antibody results immediately in the loss of skin sensitivity. All of the evidence obtained indicates that tissue hypersensitiveness in an actively sensitized animal is dependent upon the formation of antibody by the animal and is reflected by the presence of precipitin in the circulation.

The importance of antibody in the Arthus test is further brought out in the experiments upon passive transfer of hypersensitiveness. When the precipitin is absorbed from an antiserum, that antiserum loses its power to sensitize passively a normal animal. Such a serum is also unable to elicit a reaction on injection into the skin of a normal animal which has been injected intravenously with the specific antigen. The tissue sensitizing substance in an antiserum appears to be inseparable from and, probably, identical with the precipitin.

Several of these observations are contrary to those reported by Kahn in his numerous publications upon the subject and cast doubt upon the conclusions to which Kahn has been led. The existence in the skin or other organs of any sensitizing agency other than the antibody appears not to be essential for an explanation of the mechanism of the Arthus reaction. Such an agency has, furthermore, thus far not been demonstrated. The data here offered supports entirely the contention of Opie that the union of antibody with antigen is responsible for the Arthus reaction.
On the Failure of Concentrated Diphtheria Antitoxin to Give the Ramon Flocculation Reaction with Toxin
Authors: Eagle Harry
Published: January 2023

No satisfactory explanation has yet been offered for the fact that highly refined and concentrated solutions of pseudoglobulin prepared from diphtheria antitoxin frequently do not give the Ramon flocculation reaction with toxin, despite the fact that their biological activity as measured by protection experiments on guinea pigs may greatly exceed that of the original serum.

The following experiments were undertaken in order to ascertain whether the absence of flocculation is due to the failure of the antitoxin globulin to combine with toxin in vitro.

Varying quantities of anti-diphtheria horse serum pseudoglobulin were added to one L+ dose of toxin, the mixture was allowed to stand for one-half hour, and the globulin was then precipitated by the addition of a rabbit anti-horse serum. The latter was added until the supernatant fluid contained demonstrable excess of the anti-horse serum antibody, and no demonstrable horse serum protein. The mixture was then centrifuged, and the supernatant fluid tested for its toxin content.
Experiments on Reactivation of the Virus in Neutral Serum-Virus Mixtures
Authors: Goyal Ram Kumar
Published: January 2023

Summary and Conclusions

Antigen-antibody union occurring in vitro was demonstrable in overneutralised serum-virus mixtures. More or less balanced mixtures were reactivable. There was no evidence of in vitro union in such mixtures. The speed of inactivation of the virus was unlike the slow neutralisation of a toxin by the corresponding antitoxin and could be compared to the destruction of bacteria by specific antisera. Inactivation of the louping-ill virus in vivo by the corresponding antiserum could be effected without any in vitro contact.

No major differences have been elicited between the mechanism of anti-viral and anti-bacterial immunity.
A Study of the Generalized Shwartzman Phenomenon
Authors: Apitz Kurt
Published: January 2023

Summary and Conclusions

When rabbits are given intravenous injections of certain bacterial culture filtrates at the beginning and at the end of a period of twenty-four hours, death follows within forty-eight hours after the second injection. At autopsy, characteristic changes in the kidney and hemorrhagic diathesis are frequently noted. An investigation of certain of the factors involved in this phenomenon revealed an almost complete parallelism with those concerned in the hemorrhagic skin reaction (Shwartzman phenomenon). These findings therefore appear to justify its designation as the “generalized Shwartzman phenomenon.” Local and generalized Shwartzman reactions represent different localizations of the same type of injury. Additional evidence has been obtained which indicates that a single injection of a potent bacterial filtrate is sufficient to produce regularly a generalized Shwartzman phenomenon in pregnant rabbits.
Chemical Study of the Pollen-Sensitizing Antibody Combination
Authors: Stevens Franklin M.
Published: January 2023

Following the observation of Prausnitz and Küstner in 1921, that the sera of “protein sensitive” patients were capable of passively transferring specific sensitivities to the skin of most normal people, controversy arose concerning the nature of the antibody. While some immunologists believed that this antibody was identical with the anaphylactic antibody, others, notably Coca, were of the opinion that the two were not the same. He has recently (1) summarized his reasons, based on his own experimentation as well as that of his contemporaries, for believing in the existence of two distinct antibodies endowed with different qualities. He points out that the antibody found in the sera of “protein sensitive” patients is characterized by its human origin, by its specific property of sensitizing the human skin, its inability to passively sensitize the uterus of the guinea pig, and its peculiar inability to render the related “atopen” inactive.
Experiments Upon the Passive Transfer of Antibodies from the Blood to the Cerebrospinal Fluid
Authors: Kolmer John A. , Sekiguchi Shigeki
Published: January 2023

The removal of blood from normal dogs followed by the intravenous injection of human syphilitic serum in amounts varying from 30 to 50 cc. per kilogram of body weight was followed by the presence of small amounts of syphilis reagin (the antibody concerned in the Wassermann reaction) in the cerebrospinal fluid. The reagin was found in the cerebrospinal fluid as early as three hours after transfusion with syphilitic serum; tests at shorter intervals were not made. The amount of reagin found in 0.5 cc. of cerebrospinal fluid was small in all experiments as based upon the degree of complement fixation with all antigens. After irritation of the spinal meninges by the preliminary injection of sterile horse serum the amount of reagin gaining access to the cerebrospinal fluid after transfusion of syphilitic serum, appeared to be somewhat greater. All traces of syphilis reagin in the cerebrospinal fluid of dogs following transfusion of human syphilitic serum apparently disappeared after 22 to 48 hours as determined by completely negative Wassermann reactions. The intravenous injection of dog-typhoid immune serum into a normal dog in amount of about 30 cc. per kilogram of body weight, was followed by the appearance of traces of agglutinin in the cerebrospinal fluid within three hours after transfusion; fluid removed forty-eight hours later was free of agglutinin. These experiments demonstrate the possibility of the passage of antibody from the blood into the cerebrospinal fluid without primary involvement of the central nervous organs or injury to the mechanism concerned in the production of cerebrospinal fluid, when the amount of antibody in the blood has reached a point of high concentration. While it is possible that in human syphilis the presence of traces of reagin in the cerebrospinal fluid may be due to the passive transfer of this substance from the blood, as shown by Wile and Stokes the presence of the reagin with or without other changes in the fluid, as an increase of protein and cells usually indicates the presence and activity of T. pallida in the tissues of the central nervous organs.
The Isolation, Purification and Concentration of Immune Bodies: A Study of Immune Hemolysin
Authors: Kosakai M.
Published: January 2023

The reversibility of the antigen and amboceptor union is proved to be practically complete, so far as the immune hemolysin of the rabbit against sheep's blood is concerned. The isolation of hemolytic amboceptor from its antigen union is accomplished by a simple method: When the hemolytic power of the original immune serum is 1:10,000, it is diluted to 100 times its volume with physiological salt solution; 5 cc. of this diluted serum is poured into 4 cc. blood cells, which are washed free from serum protein with physiological salt solution. After 15 to 20 minutes at room temperature all of the hemolytic amboceptor has been adsorbed by blood cells; and the antigen-amboceptor union is thus obtained. After the sensitized corpuscular sediment is washed with physiological salt solution several times, till the last trace of serum protein has been removed, this pure antigen-amboceptor combination is mixed with an isotonic or slightly hypertonic watery solution of saccharose, glucose or lactose and left at 55°C. for fifteen to thirty minutes, during which time the vessel is shaken several times. The sugar extract, which contains nearly all of the hemolysin used to sensitize the cells, is obtained by centrifugation. In order to purify this sugar extract, which contains substances from destroyed blood cells, it is placed in a separatory funnel and shaken for one to two hours with 5 to 10 volumes of ether, this treatment, if necessary, being repeated twice or thrice, till at last the solution becomes quite colorless. This colorless solution is dialysed in parchment against running water in order to eliminate the sugar and traces of ClNa. The solution thus obtained is concentrated in vacuo to the required volume.
The Immunologic Properties of Uveal Pigment
Authors: Woods Alan C.
Published: January 2023

In the course of a detailed study of the anaphylactic theory of sympathetic ophthalmia, a study has been made of the antigenic properties of the uveal tract, especially the uveal pigment, of the eye. From the standpoint of the ophthalmologist the results are of little import beyond their possible correlation with clinical disease. From the standpoint of the immunologist, however, the results appear to be of more scientific interest, in so far as they indicate rather striking immunologic properties for a native body protein. It is, therefore, the purpose of this paper to report the results of this phase of our studies.

The anaphylactic theory of sympathetic ophthalmia, advanced and advocated by Elschnig, assumes that sympathetic ophthalmia is an anaphylactic uveitis brought about in the following manner. The injury to the uvea in the exciting eye, by trauma, intraocular tumor, etc., leads to a destruction or disintegration of uveal tissue.
The Examination of the Blood Preliminary to the Operation of Blood Transfusion
Authors: Coca Arthur F.
Published: January 2023

Before the operation of blood transfusion is carried out it is necessary to test the compatibility of the prospective donor's blood with that of the patient; that is, it must be determined whether the blood corpuscles of the donor will remain intact in the circulation of the patient. It is altogether probable that no two human individuals possess blood having exactly the same chemical composition; indeed, the possible different combinations of demonstrated different substances in the corpuscles alone have been estimated to be about 4000 (1).

Fortunately, however, the differences in the blood plasma and most of those in the corpuscles, although they are, perhaps, the cause of certain unpleasant symptoms, such as a chill followed by a rise of temperature, do not constitute an incompatibility such as could contraindicate the use of the blood of an individual for transfusion.
Experiments on the Production of Antipoliomyelitic Serum in Rabbits
Authors: Tsen Edgar T. H.
Published: January 2023

One can find in the extensive literature on experimental poliomyelitis only a few scattered statements of experiments on the production of antipoliomyelitic serum in rabbits, and these statements, furthermore, are as contradictory as those regarding the question of the etiology of poliomyelitis and the susceptibility of rabbits to this disease. Flexner (1), in 1910, stated that rabbits which had been given injections of active poliomyelitis virus did not seem to yield immunity principles that had restraining or neutralizing effect on the virus either in vitro or within the body. Amoss (2), in 1917, reported that the serum of rabbits which he had injected intravenously with a heavy suspension of washed cultures of globoid bodies also failed to neutralize the filterable virus. On the other hand, Nuzum (3) claimed that he had succeeded in producing antipoliomyelitic serum in rabbits by immunizing them with strains of streptococci which he and several others believed to be the causative agents of poliomyelitis.
Prompt Macroscopic Agglutination in the Diagnosis of Glanders
Authors: Povitzky Olga R.
Published: January 2023

A method has been devised whereby a prompt clear cut macroscopic agglutination for the diagnosis of glanders can be obtained in two hours. Fifteen strains of B. mallei were tested and one obtained which is constant in its agglutinability with positive sera. The best culture medium is glycerin-potato-agar (2.5 acid to phenolphthalein) carefully prepared (see text). Great care must be used in the preparation of the stock suspension of B. mallei (see text). For the tests, fresh dilutions in 0.85 per cent salt solution are made from the stock suspension. No carbolic acid is added to the stock nor to the dilutions. The agglutination test is valuable in the routine examination of horses. With this test nearly all early and acute cases can be detected and thus the spread of the disease can be prevented. A negative reaction by a single agglutination test if not confirmed by the ophthalmic and the complement fixation tests does not prove the case negative; nor does a single negative result either by the complement fixation or ophthalmic tests. A positive reaction by any of the three methods is more significant than a negative one. All three tests must be performed in order to pronounce the horse negative. In my experience with the present series of cases a reaction of less than 1:1000 by agglutination (if the other two tests are negative and if there are no clinical symptoms) is not indicative of glanders in the horse. If the reaction is above a 1:1000 the horse should be kept under observation; even if he does not show active glanders, the possibility of a carrier condition should be thought of. Isolation of such horses would be a very safe measure for preventing the infection among the other horses. The bacteriological method of inoculating the guinea-pig with glanders material for the “Strauss” reaction is successful in only 25 per cent of cases (active lesions). Autopsy findings, if possible, should be confirmed by pathological sections. A great many cases are pronounced glanders on autopsy, which do not show typical lesions under the microscope. All stables should be under the supervision of the City Health Department and glanders in horses should be put in the same category as typhoid, meningitis, etc. in man, if glanders in New York City is to be eradicated. Sera that come to the Health Department for diagnosis should be accompanied by a complete history of each horse. Follow up work should be possible. Records of the three tests and autopsy findings should be accessible and some mark of identification for every horse should be devised by which all records of a horse can be compared. Only in some such way can a really scientific study of the disease be made and the right conclusions drawn.
Quantitative Studies on the Neutralization of Equine Encephalomyelitis Virus by Immune Serum
Authors: Merrill Malcolm H.
Published: January 2023

Summary and Conclusions

The addition of subneutralizing doses of immune serum to suspensions of equine encephalomyelitis virus caused a definite decrease in the titer of the virus, indicating a 90 to 99 per cent neutralization. This occurred over a wide range of serum-virus ratios. In the narrow zone of serum-virus ratios in which neutralization was complete there was a direct relationship between the number of infective doses of virus present and the serum required for neutralization. It is believed that two phenomena were being measured, namely, aggregation and neutralization, and it is suggested that the phenomenon of percentage neutralization with the virus in question, as well as with phage, is probably due to aggregation of virus, or phage, particles.
Hemolytic and Combining Capacities of Pneumococcic Extracts
Authors: Hull Winifred S.
Published: January 2023

Pneumococcic extracts, prepared from 9 different strains of pneumococcus, have been studied with regard to their hemolytic power and capacity for combining with antibody. It has been shown that the combining capacity of the individual extract remains constant over a long period of time, although there is a progressive decrease in the ability to hemolyze red blood cells.
Alum-Precipitation of Diphtheria Toxoid (Improvement of Diphtheria Alum-Toxoid)
Authors: Ando K. , Komiyama T. , Manako K.
Published: January 2023

Precipitation of diphtheria-toxoid by alum depends on the pH under which the precipitate is formed. Purified toxoid requires much less amounts of alum to be precipitated than the original toxoid. One-eighth by volume of 4 per cent solution of alum seems to be sufficient for toxoid purified with calcium-phosphate to precipitate the greater part of the active principle from it. The superiority of the alum-toxoid as an immunizing agent was shown with toxoids purified with calcium-phosphate.
Active Immunization to Scarlet Fever by the Intracutaneous Method
Authors: Robinson J. Hudson
Published: January 2023

The administration of scarlet fever streptococcal toxin in effective dosage for active immunization is often followed by undesirable local and general reactions when the injections are made by the usual subcutaneous route.

Evidence has been accumulating that the skin may be utilized advantageously as a route of absorption for various vaccines and toxins in producing active immunity. In 1931 Tuft (1) compared the antibody-response following 4 weekly injections of mixed typhoid vaccine by the subcutaneous, intramuscular and intracutaneous routes in human beings. Subsequent serologic study of these individuals showed that the degree of antibody-production was equal to that found after the use of the other routes of injection. The total number of bacteria injected intracutaneously was one-seventh the number injected by the other routes. Tuft remarks upon the relatively “large number of negative or slight (one plus) local reactions after intradermal injection” and “the extremely low percentage of the constitutional symptoms occurring after the intradermal injections as compared with the others.”
Complement Fixation Following B.C.G. Vaccination
Authors: Reed G. B. , Gardiner B.G.
Published: January 2023

Previous complement fixation studies of the serum of tuberculous patients and of infected and immunized rabbits using two antigens in parallel, one prepared from the S form and one from the R form of Mycobacterium tuberculosis, have led us to the opinion that S forms of the tubercle bacillus contain antigenic components which are lacking in R forms. The reaction of a small group of human cases to vaccination with B.C.G. lends some support to the view that antigenic deficiencies occur in the constitution of B.C.G.

Dr. R. S. Ferguson of the Saskatchewan Anti-Tuberculosis League kindly sent us the sera of 11 Indian children ranging in age from 9 to 16 years. These children had received 0.3 mgm. of B.C.G. vaccine intracutaneously (living culture prepared according to Calmette's method). Each developed a characteristic local infection of approximately the same intensity.
On the Mutual Multivalence of Toxin and Antitoxin
Authors: Eagle Harry
Published: January 2023

Summary and Discussion

Diphtheric toxin and antitoxin do not necessarily combine in a fixed proportion to form a “neutral” compound, as postulated by Ehrlich and by Arrhenius and Madsen. Conforming to other antigen-antibody systems, both reagents seem multivalent with respect to each other. In the presence of an excess of toxin, antitoxin binds several times as much toxin as is indicated by its neutralizing activity, and the resulting compound is itself toxic. Similarly, in the presence of excess antitoxin, toxin combines with more than the neutralizing quantity of antitoxin to form an antitoxic compound. The precisely neutral compound, instead of being the usual type of combination, is formed only when the two reagents are mixed in just the proper proportions. The present experiments offer no clue as to the stoichiometric ratio between toxin and antitoxin at this point of equivalence (neutrality); nor do they indicate the number of reacting groups which bind each molecule of toxin and antitoxin at the equivalence point.
Further Studies on the Immunology of Hemophilus Pertussis
Authors: Powell H. M. , Jamieson W. A.
Published: January 2023

Additional data has been presented on successful enhancement of virulence of H. pertussis. Pertussis vaccines may be tested in mice in a relatively inexpensive way. Successful results in mice have yet to be correlated with satisfactory clinical results in human beings. Several passive protection tests in mice inoculated with H. pertussis have been described.
Further Investigations on the Blood-Brain-Barrier
Authors: Friedemann Ulrich
Published: January 2023

Summary and Conclusions

After intravenous injection into guinea pigs weighing 300 grams all basic aniline dyes with the exception of safranine stain the brain in amounts ranging from 1 to 7 mgm. Some acid dyes (acid fuchsin, orange, bordeaux, eosin, uranine) do not stain the brain at all in the available amounts. Some others (trypan blue, congo red, water blue, alizarin blue-S, indigo di- and tetrasulphonate) stain in amounts varying from 20 to 80 mgm. The difference between basic and acid dyes is partly due to a difference in their affinity for brain tissue. The latter was tested by determining the minimal staining dose in vitro (Cv). In addition the cerebral capillaries are more permeable to basic than to acid dyes. This permeability can be determined by the ratio between the minimal staining concentrations in vivo and in vitro (CB/Cv). The permeability of the cerebral capillaries to dyes is independent of their chemical constitution, their size and their lipoid solubility. It merely depends on their electrical charge. Staphylococcus toxin acts rapidly without any incubation period. It is unable to pass the blood-brain-barrier. Staphylococcus toxin carries a negative charge at the pH of the blood. The isoelectric point is in in the neighbourhood of pH 6.2. A special method has been devised to compare the ζ-potentials of toxins. The capacity of toxins to pass the capillary system is correlated with their ζ-potentials. Tentatively, a theory is advanced according to which the selective permeability of the capillary system in general and the blood-brain-barrier in particular is due to an irreciprocal permeability.
On the Differences in Activity of Serum Complement from Various Animal Species
Authors: Shrigley E. W. , Irwin M. R.
Published: January 2023

Summary and Conclusions

The normal sera of ox, rabbit, and sheep were found to be highly bactericidal for Brucella suis, while normal guinea pig serum showed no such activity. The bactericidal activity of the above sera was destroyed by heating at 56.5°C. for 30 minutes or by absorption with heat-killed Brucella suis. Guinea pig complement would not activate the normal thermostable antibody of ox, rabbit, or sheep serum against Br. suis. Rabbit complement activated only heated rabbit serum. Ox complement activated almost completely the killing power of heated sera of the rabbit and ox, and only partly that of the heated sheep serum. Sheep complement restored completely the bactericidal power of heated normal sheep and rabbit sera, and activated heated ox serum nearly to the same degree as did ox complement. The order of these complements arranged according to their ability to activate certain normal bactericidins is just the opposite to a similar arrangement for complements in hemolytic systems. Our data show that complements vary in their ability to activate normal bactericidins against Brucella suis, and therefore the complements from different animal sources are not always interchangeable in normal bactericidal reactions.
Heredity of Agglutinogens M and N Among Pueblo and Blackfeet Indians
Authors: Allen Fred W. , Larsen Harold D.
Published: January 2023

Summary and Conclusions

The theory that the inheritance of the agglutinogens M and N of Landsteiner and Levine depends upon a single pair of allelomorphic genes was tested by determining the frequencies of the three types (M+N+, M+N−, M−N+) in 140 pueblo Indians, and also by similar data for Blackfeet Indians given by Matson, Levine, and Schrader.

The frequencies of the genes were determined by the formulae: and where m and n are the frequencies of the genes M and N respectively. The size of the deviation, D = (m+n)−1, was compared with its probable error and found to be insignificant in both cases.

Therefore, this is taken to be evidence in favor of the theory of Landsteiner and Levine, which states that the inheritance of the agglutinogens M and N depends upon a single pair of allelomorphic genes.
Toxins of Salmonella Aertrycke
Authors: Herter Ruth C. , Rettger Leo F.
Published: January 2023

Introduction. In the epidemics of paratyphoid infection in turkeys reported by Rettger, Plastridge and Cameron (1933) the mortality was as high as 65 per cent. The etiological agent was found to be Salmonella aertrycke. The organism was highly pathogenic for young turkeys, chicks, guinea pigs and mice, when administered orally and parenterally.

The question as to whether or not toxins play an important rôle in producing symptoms and fatalities resulting from infection with bacteria of the paratyphoid group has been a matter of interest for some time. However, the existence of a toxin that is specific for the natural host has apparently not been demonstrated for members of the paratyphoid group. It is true that other investigators have obtained toxic substances in culture filtrates and autolysates, but animals other than the natural host were employed by them. In studying the toxin production of S. pullorum, Hanks and Rettger (1931) failed to obtain a toxin which was capable of killing young chicks.
A Low Temperature Ball-mill for the Liberation of Labile Cellular Products
Authors: Mudd Stuart , Shaw C. H. , Czarnetzky E. J. , Flosdorf Earl W.
Published: January 2023

The problem of disintegration of cells and tissues for the purpose of liberating intracellular substances arises in many fields. It has become increasingly apparent, particularly in the field of bacteriology, that classical methods to this end have been only partially successful, and that many of the products obtained have been in reality artefacts, degradation products of the more complex and biologically active substances present in the intact cells.

A short time ago, an article by one of us (E. J. C.) appeared in Science, in which the extraction of labile bacterial antigen by disruption of the lyophile-dried bacterial cells at low temperature (1) was described. This method utilized liquid air to bring the bacteria to a temperature beyond a critical point at which the dry bacteria become brittle and are easily disrupted by mechanical agitation with a mortar and pestle.
The Nature of Antibodies
Authors: Hooker Sanford B.
Published: January 2023

Upon occasions like this there is only one person who is obliged to address the meeting. In partial compensation he is permitted to indulge rather freely in imaginative flights and, when he returns to earth, he is at least temporarily immune to the critical discussion that the unprotected voluntary speaker must be prepared to endure. It has been considered appropriate for him to review some subject of specialized interest to the gathering.

For these reasons I have ventured to speculate upon the nature of antibodies. This title is even more pretentious than it seems at first glance, because we can not even define antibody without using such a comprehensive term as antigen, and it is impossible to discuss either without continual reference to the intricate concepts of immunochemical specificity.
The Cutaneous Reaction of Rabbits to Pneumococcal Vaccines and Its Neutralization by Specific Antisera
Authors: Weil A. J. , Phillips S. W.
Published: January 2023

Vaccines, made from young cultures of pneumococci evoke an infiltration in the skin or rabbits when injected intracutaneously in comparatively small quantities. The irritating substance is heat labile, and loses activity as the cultures grow older. S-substance does not cause a similar reaction. This reaction is prevented specifically when antipneumococcal serum is injected simultaneously with the vaccine. The neutralization is strictly type-specific and allows a quantitative estimation of the antibody content within a range of ±20 per cent.
Passive Anaphylactic Sensitivity to Pneumococcal Capsular Polysaccharides
Authors: Goodner Kenneth , Horsfall Frank L.
Published: January 2023

These results suggest by inference that fatal passive anaphylactic sensitivity to pneumococcal capsular polysaccharides is obtainable with proportions of antigen to antibody in which the amount of carbohydrate is slightly in excess of the amount necessary to satisfy the available antibody. If the proportion of antigen is excessively large a negative result is obtained. If the amount of antigen is too small a similar negative result is obtained, and this is true in a region of combinations in which positive complement-fixation might be expected.
The Titration of Alpha and Beta Haemolysins in Staphylococcal Toxin
Authors: Roy T. E.
Published: January 2023

The haemolytic action of staphylococcal toxin on human erythrocytes has been described. It is a “hot-cold” lysin.

This haemolysin is antigenically distinct from the Alpha haemolysin, and is probably identical with the Beta toxin of Glenny and Stevens. The only material difference between our haemolysin and that described by Glenny and Stevens is that ours lyses rabbit cells.

The presence of more than a certain concentration of Beta toxin lowers the apparent titer of Alpha antihaemolysin in terms of Provisional International Units and is therefore misleading. The converse is also true. It would seem essential to take this into account in the haemolytic method of assaying therapeutic antisera as a standard.

The mutual interference of Alpha and Beta toxin in the titration of antitoxin can be eliminated by suitable dilution of selected toxins, but this method is limited by the concentration needed to give accurate results. This method is of least value in titrating Alpha antitoxin because of the susceptibility of rabbit cells to Beta toxin, and it is most desirable to use a pure Alpha toxin.

The use of human erythrocytes in the titration of Beta toxin and Beta antitoxin has great advantages over the use of sheep erythrocytes. They show considerable resistance to the Alpha haemolysin whereas sheep cells are very susceptible to it. This being so, impure toxins can be used to titrate any Beta antitoxin if the test dose of toxin used contains less than one LH dose of the Alpha toxin.
The Production of Diphtheric Antitoxin in Tissue-Cultures
Authors: Hwon Tsai Len
Published: January 2023

It has been known for a long time that antibodies can be produced by tissues cultivated in vitro. Carrel and Ingebrigtsen (1) cultivated lymph-node and bone-marrow tissues of the guinea pig in homologous plasma to which goat's erythrocytes were added, and reported the development of hemolysin. Lüdke (2) cultivated splenic tissue from rabbits who had been injected with ox or goat-erythrocytes, dysenteric or typhoid vaccine, and found hemolysins and agglutinins. Schilf (3) found bacteriolysins to vibrio cholerae, and Meyer and Loewenthal (4) proved that agglutinins are present in cultures of spleen, lymph-node, etc. R. Kimura (5) found agglutinins for B. coli, and precipitins for chicken and rabbit-sera. Many of the subsequent studies on the subject of antibody-production in tissue-cultures have been made in our Institute, and relate to hemolysin (6), precipitin (6), bacterial agglutinin (6, 7, 10), hemagglutinin (8), bactericidin (7), anaphylaxis antibody (8), virulicidal substance (9) and complement-fixation antibody (10).
Age and Antibody-Production
Authors: Baumgartner Leona
Published: January 2023

A difference in the reactivity of antisera produced in animals of various ages has previously been suggested (2, 3) on the basis of so-called avidity-experiments in agglutinating and hemolytic systems. Avidity was used to designate differences in the rate of appearance of flocculation (or hemolysis). Different degrees of flocculation at intermediate periods were contrasted with the final flocculation observed at an arbitrarily chosen end-point of twenty-four hours and the observed differences in the rate of appearance of the flocculation were taken to be indicative of qualitative differences in the antisera concerned. The avidity of fresh antisera agglutinating B. enteriditis was found to be greater in adult than in young (500 to 700 grams) rabbits. Some experiments indicated that hemolytic antisera showed the same characteristics.

It seems desirable further to investigate the possibilities of differences in the reactions of sera from animals at different ages.