bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antigenic Structure of Hemolytic Streptococci of Lancefield Group A
Authors: Pappenheimer A. M. , Williams J. W. , Zittle C. A.
Published: January 2023

The molecular weight of the type-specific M-protein isolated from group A hemolytic streptococcus is 41,000. The molecule is an extremely elongated one with an axial ratio close to 25 to 1. As expected from the large axial ratio, solutions of M-protein show high viscosity.
Separation and Determination of Multiple Antibodies
Authors: Haurowitz Felix , Vardar Muzaffer , Sarafyan Kirkor , Tunca Mürvet , Uzman Lahut , Schwerin Paula
Published: January 2023

Immunization with each of 8 homogeneous antigens led to the formation of multiple antibodies. This is attributed to a different degree of adjustment of the antibody-molecules to particular factors (sub-groups) within the determinant group of the antigen. The bonding force of determinant arsenic-acid groups is stronger than that of sulfonic-acid groups, probably because of their higher ionic strength. A positively charged azoprotein with quaternary ammonium groups proved to be just as powerful an antigen as arsanil-azoproteins. The determinant group of substituted proteins (azoproteins, iodoproteins) includes also a portion of the protein-molecule. We distinguish 3 types of antibodies: a) low-grade, b) imperfect and c) special antibodies. Imperfect antibodies are precipitated only by the homologous antigen, special antibodies by the homologous as well as by heterologous antigens containing the adequate determinant factors. A rational nomenclature for the multiple antibodies of an immune serum is proposed. We designate each antibody by the determinant factors indispensable for its precipitation. The amount of different antibodies in two immune sera to azoproteins has been determined (table 4 and 5). The essential reasons for the attachment of antibody to antigen are briefly discussed.
The Inhibitory Effect of Human Serum Upon the Isoagglutination of Red Cells
Authors: Lubinski Herbert H.
Published: January 2023

Summary and Conclusions

Diluting a hemagglutinating serum with an antagonistic or previously absorbed hemagglutinating serum instead of with saline solution diminishes the titre of agglutination considerably, in some cases to zero. Since this result can be achieved by any human serum freed of agglutinins, even by sera of the same type and by O serum, therefore it cannot be considered as caused by the type-specific substances (agglutinogens), but must be caused by an unspecific factor which can be found in different degree in any human serum. Heating to 56 C for one-half hour does not affect this factor.
Species-Specific Precipitins in Serum Sickness after Intravenous Injection of Refined, Concentrated Antipneumococcal Rabbit Serum
Authors: deGara Paul F. , Bullowa Jesse G. M.
Published: January 2023

The sera of 20 pneumonic patients treated intravenously with refined and concentrated rabbit antipneumococcal serum were examined on several occasions after the treatment. Circulating species-specific precipitins for rabbit protein were detected between the 6th and the 21st day after the intravenous serum treatment in the sera of 10 patients (50 per cent).

The precipitative antibodies were detected in one patient on the 6th day after the intravenous serum treatment. In the remaining patients they appeared between the 9th and the 11th day and disappeared from the circulation 20 to 22 days after the intravenous injection. They were found most frequently between the 12th and the 18th day, usually when other symptoms of serum sickness had already disappeared. There was no direct relationship between the amount of seurm injected (10 to 109 ml) and the appearance of precipitins.

Precipitins were not detected in the sera of 20 control patients, suffering from pneumonia and treated with antipneumococcal rabbit serum (5 to 237 ml), who did not show clinical manifestations of serum sickness.

Our observations conform with reports on the presence of antibodies in serum sickness due to horse-serum injections (10). The precipitin-reaction may confirm the diagnosis of serum sickness, but the absence of circulating precipitins does not exclude it. It may be found after the symptoms have disappeared.
Evidence of Serological Heterogeneity of Polyvalent “Pure Line” Bacteriophage
Authors: Kalmanson G. M. , Bronfenbrenner J.
Published: January 2023

By means of careful neutralization of polyvalent PC phage acting on B. coli, B. dysenteriae Shiga, and B. dysenteriae Flexner, it has been possible to neutralize the “valences” for the latter two organisms and to secure a monovalent phage acting on B. coli only. This monovalent phage promptly regains its polyvalence when it has acted upon B. coli.

It has been shown that the valence for B. dysenteriae Shiga is neutralized at a faster rate than the coli valence. The difference in rates is probably not due to the fact that it may take a different minimum number of antibody molecules to neutralize a valence for B. coli than that for B. dysenteriae Shiga.
The Antigenic Structure of Hemolytic Streptococci of Lancefield Group A
Authors: Wiener Maria , Zittle Charles A. , Mudd Stuart
Published: January 2023

The studies described lead to the conclusion that the M-protein is definitely antigenic even though subjected to drastic methods of isolation and purification. The isolated M-protein is not nearly as antigenic, however, as intact streptococci which are believed to contain a fiftieth or less of their weight as M-protein.
The Effect of Separate Inoculation of Serum and Virus Upon the Protection-Test in Vaccinia
Authors: Green Robert H. , Parker Robert F.
Published: January 2023

That the serum of an animal actively immunized to a virus may afford some protection against infection when a mixture of that serum and active virus is injected into a susceptible animal is commonly accepted. It is also generally agreed that immune serum, injected at a suitable period of time before inoculation of the infectious agent, may afford passive protection. On the other hand, the ability of immune serum to protect, when it is administered subsequent to the inoculation of the infectious agent, has not been uniformly conceded. Andrews (1) showed that vaccinal immune serum injected into a rabbit's skin 24 hours before the intracutaneous inoculation of vaccine virus prevented the appearance of a lesion, provided that the dose of virus was not too large. In a later paper (2), he also showed that immune serum injected as long as 4 hours after the injection of virus modified the course of the disease in that the lesions were smaller than those appearing at sites injected with virus only.
Monovalent and Polyvalent Sera in the Treatment of Pneumococcal Infections
Authors: Forster George F. , Noblitt Ernest H. , Gilman Edward N.
Published: January 2023

Against the multiply reacting Hoge strain of pneumococci a monovalent type 29 serum was found to exercise almost as great protection (in mice) as a polyvalent mixed serum potent against types 29, 10, and 20 (three types with which the Hoge strain is cross-reactive). A serum prepared against the Hoge culture as an immunogen afforded somewhat greater protection than either the polyvalent mixture or the monovalent type 29 serum. The anti-Hoge serum was also highly effective in protecting mice against type 29 culture and in less degree conferred protection against types 10 and 20 pneumococci. A highly potent serum was prepared by immunizing a rabbit against the avirulent Weingart strain which cross-reacts with types 31, 20, and 29. Because of the extremely low virulence of the homologous strain the protective power of the anti-Weingart serum could not be demonstrated against the homologous culture, but was shown to be protective in high degree against virulent type 31 pneumococci and to a lesser extent against types 20 and 29. The same features were brought out in comparing the reciprocal protective values of antisera prepared against types 10 and 10A, the latter being of very low virulence, the former high. The advantages to be derived from the use of broadly polyvalent sera in pneumonia therapy were outlined and the possible value of multiply reacting strains in the production of such sera was indicated.
The Hypothermic and Adreno-Hemorrhagic Effects of Bacterial Vaccines
Authors: Olitzki L. , Avinery Sh. , Koch P. K.
Published: January 2023

The data presented above indicate that the adreno-hemorrhagic and hypothermic factors are present only in certain groups of microorganisms. The differences in the reactions produced by the various groups of microorganisms seem to be due to their different chemical composition. Heavy reactions were produced by less than 1 mg of certain Eubacteriales, but could not be produced even by large amounts of organisms belonging to the Mycobacteria. In general, the hypothermic, hemorrhagic and leucopenic (cf. 1) reactions were associated, although they varied intensity; in the case of some organisms, 1 mg produced hemorrhages without hypothermia, and in others this amount produced hypothermia without leucopenia.

These reactions are influenced by unspecific factors, and there are also some differences in the sensitivity of the various laboratory animals. The leucopenic reaction appeared in guinea-pigs, as well as in rabbits, independently of the age of the animals. Rabbits weighing more than 2000 g showed severe leucopenic reactions. The other endotoxic reactions could be produced regularly only in guinea-pigs under 300 g. In addition, there exists an individually varying degree of resistance, the cause of which is not clear.

One injection of bacterial vaccine or of normal serum and plasma from rabbits or from guinea-pigs was followed by a period of nonspecific resistance to the injection of bacteria that contain the hypothermic and hemorrhagic factor. The hypothermic reactions were again elicited two or three days after the injection of the sera or 12 days after the injection of the vaccine. Within this period the hemorrhages appeared only in few animals. The leucopenic reactions could be prevented only for two days by the injection of vaccine, and in guinea-pigs, in contrast to rabbits, serum or plasma treatment was entirely ineffective. Thus, these animals showed isolated leucopenic reactions without hypothermia and without hemorrhages in the adrenals. This harmonizes with the greater sensitivity of the leucocytes to the action of the endotoxin.

In the active immunization experiments, the period of nonspecific resistance following vaccine treatment must elapse. Our tests were made 12 days after the last injection. Under these conditions some evidence for acquired resistance against the hypothermic action of bacterial vaccine could be obtained; there was, however, no indication that the adreno-hemorrhagic effect was influenced by the same amount of previous treatment with homologous vaccine.

In the passive immunization experiments, a period of at least two days must elaspe to exclude the nonspecific effect of the sera. After this period a specific protecting effect of the serum was not observed.
Nonspecific Factors in Resistance
Authors: Brown WM. B. , Graham Irma , Niedringhaus Ariel , Locke Arthur
Published: January 2023

An investigation is reported which extends the evidence recently reported by Coca for the existence of a cause-and-effect relationship between presence of nonreaginic food-allergy and predisposition to common cold. Two or more of Coca's 11 symptomatic evidences of the presence of nonreaginic food-allergy were found to be present in 79 per cent of a group of 422 girls of college age. Each of the symptoms, when present, was associated on the average with a higher colds-incidence than was observed in the absence of symptoms. A progressively higher colds-incidence was found with increasing number of symptoms. No correlation was found between presence of symptomatology and percentage appearing to be in poor condition on a basis of performance during a modification of the Flack test. Handicap from poor condition, appraised as described, was, however, reflected in a heightened colds-incidence as was handicap from addiction to smoking. The girls with the greatest total handicap, from all sources, had roughly 4 times as many colds as those with the least.
Allergy and Immunity in Tuberculosis
Authors: Steiner Morris , Zuger Bernard
Published: January 2023

The experiments reported in this and the succeeding paper deal with the longstanding problem of the relationship of tuberculin cutaneous reactivity to resistance to tuberculous infection. The opportunity to add to the already considerable literature on the subject presented itself as a result of the work of Steenken, Oatway and Petroff (1) who effected the dissociation of a rough avirulent variant from the virulent human strain of tubercle bacillus H37. These authors found that the avirulent variant produced little tissue destruction but was nevertheless capable of inducing good cutaneous sensitivity and immunity in guinea-pigs (2).

In the present paper the character of the immunity induced by the avirulent strain is described. The paper that follows is concerned with the possible influence upon this immunity of the tuberculin cutaneous sensitivity present at the time of reinfection with the virulent test dose.
A Toxic Ocular Reaction
Authors: Ayo Corrado
Published: January 2023

Summary and Conclusions

The work embodied in this paper demonstrates that Shwartzman toxins are capable of producing a primary ocular reaction in rabbits, named the toxic ocular reaction. The reaction consists of intense iridoconjunctival hyperemia and coagulation of the aqueous humor after its aspiration. It appears several minutes after the intravenous injection of toxin, reaches its maximal intensity in a few hours, and is notably reduced or has completely disappeared in about twelve hours. The smallest amount of toxin which, by intravenous injection, induces aqueous humor coagulation is termed the minimal coagulating dose.

The reaction was also obtained using the intra-arterial and intraabdominal routes and a highly vascularized area of the skin. However, the intestinal and conjunctival routes proved non-effective.

Protection against the ocular reaction was afforded by previous intracutaneous or intravenous injection of rabbits with Shwartzman filtrates or by moccasin snake venom injection.

Toxins kept their potency for several months when undiluted preparations were stored in the refrigerator. The toxic ocular principles did not pass through dialyzing membranes, showed resistance to heat at high pressure, were definitely weakened by the addition of formaldehyde, and were specifically neutralized by Shwartzman antitoxins.

This reaction was reproduced in cats and dogs but failed to appear in other usual laboratory animals, even guinea-pigs in which, in a certain percentage, the Shwartzman phenomenon may be elicited.

The toxic ocular reaction was obtained in approximately 95 per cent of a large number of rabbits injected intravenously with 10 or more minimal coagulating doses per kilo of body weight. It thus represents a new property of the Shwartzman toxins, and indicates their marked primary toxicity for the rabbit's uveal tract.
Factors Influencing the Development of Resistance in Escherichia Coli to the Sulfonamides
Authors: Harris Jerome S. , Kohn Henry I.
Published: January 2023

The total resistance to a drug shown by a bacterium in a particular medium is defined in terms of the molar drug concentration required to inhibit the rate of growth by 50 per cent. A method of analysis is provided which permits any change in the total resistance to be assigned to either the bacterium (Rfb) or the environment (Rfe) in which the measurement of resistance is made. The application of this analysis to strains of E. coli trained to grow in media containing sulfanilamide showed the following. Strain trained on sulfanilamide in salt-glucose medium. Tested in salt-glucose medium, the increase in resistance was found to be 3-fold against both sulfanilamide and sulfathiazole. The same result was obtained when the strain was tested in peptone medium. Strain trained on sulfanilamide in peptone medium. Tested in salt-glucose medium, the strain showed a 3-fold increase in resistance to both sulfanilamide and sulfathiazole. Tested in peptone medium, however, it showed a 5.6-fold increase to sulfanilamide and a 21-fold increase to sulfathiazole. Strain trained on peptone medium, pH 7.8. Tested in salt-glucose medium, it showed little change in resistance. Tested in peptone medium it showed a 15-fold increase to the sulfanilamide and a 100-fold increase to sulfathiazole. It is concluded that the resistance of the bacterium not only depends upon the medium in which training occurred, but also upon the medium in which the measure of resistance is made. Furthermore, since the development of resistance to sulfanilamide does not always parallel that to sulfathiazole, it appears that the mode of action of these two drugs, though similar, is not identical.
Phenomenon of Local Skin-Reactivity (Shwartzman) to Organisms of the Brucella Group
Authors: Wise Bowman , Kerby Grace P.
Published: January 2023

Three strains of Brucella suis, 2 of Brucella melitensis, and 2 of Brucella abortus have been studied for their ability to elicit the Shwartzman phenomenon. Positive results were obtained with 2 Brucella suis strains, when saline supernates after centrifugalizing were used for the skin-preparatory dose, and similarly prepared E. coli material given as the provocative dose.

Ability of material prepared from brucella strains to act as the provocative factor was not demonstrated.

Comparative experiments with material prepared from E. coli as well as from Brucella suis showed that previous vaccination with the homologous organism has no influence upon the production of the Shwartzman phenomenon.
A Comparison of the Antigenic Properties of Staphylococcal Vaccine, Staphylococcal Toxoid, and the Two in Combination
Authors: Etris Samuel
Published: January 2023

Staphylococcal vaccine has been used for the treatment of staphylococcic infections for many years with varying results. Lately evidence has been presented to show that the stimulation of agglutinins, precipitins and other antibacterial substances is insufficient to protect against infections by toxigenic strains of staphylococcci (1). In recent years staphylococcal toxoid has to some extent superseded vaccine, but although clinical results obtained by the use of this product were more encouraging, it has been found ineffective in the treatment of many forms of staphylococcic infections.

While a combination of vaccine with its homologous toxoid has been suggested, and in soine instances injected together practically no experimental evidence has been presented to show the dual antibacterial and antitoxic stimulation by such a combination and the decrease of humoral antibody during the interval between doses.
Cross Protection Between Heterologous Agglutinogenic Types of Beta Hemolytic Streptococci of Group A
Authors: Evans Alice C.
Published: January 2023

Two antiserums, prepared with strain 1475 of type 6 and 1072 of type 23, were found to protect mice against infection with strains of many types.

An immunogenic group which includes strains of types 6 and 18 and one tested strain each of types 15 and 19 was established by reciprocal cross-protective tests.

Other immunogenic groupings of agglutinogenic types suggested by similarity of reactions with six protective antiserums are as follows: 23–28; 2-11-12-27-30; 9–13.
The Use of Mice in the Testing of Antigenic Power of Tetanal Toxoid
Authors: Koerber Walter L. , Mook Gertrude E.
Published: January 2023

Mice can be used for the determination of the antigenic power both of liquid and of alum-precipitated tetanal toxoid in place of guinea-pigs. An immunization-period of three weeks insures reproducible results in protective tests against 10 M MLD of tetanal toxin.

A quantitative evaluation of the antigenic power can be effected by the use of dosage-response curves, expressing the antigenic power of various toxoids in terms of a selected standard.
Large-Scale Production of Tetanal Toxin on a Peptone-Free Medium
Authors: Mueller J. Howard , Miller Pauline A.
Published: January 2023

A formula is given for large-scale production of tetanal toxin on a medium initially free from antigenic components. All materials used are commercially available. Results obtained in this laboratory from the use of this medium in lots up to twenty liters in size are presented. Discrepancies are noted between antigenicity-tests carried out by the writers and at the National Institute of Health. These are being investigated. Experiments directed toward an understanding of the factors, other than iron, which limit toxin-production are being continued.
Experiments with Bacteriophage Supporting the Lattice-Hypothesis
Authors: Hershey A. D.
Published: January 2023

Sensitized coliphage adheres firmly to a specific precipitate of coliphage; sensitized staphylococcal phage does not, nor does sensitized coliphage stick to heterologous specific precipitates. A reaction which is also specific can be shown to occur between sensitized and unsensitized phage in solution. These facts can only be explained in terms of the lattice-hypothesis and multivalence of antibody.

The weak adsorption of sensitized phage to heterologous specific precipitates is quantitatively very similar to the adsorption of sensitized (or unsensitized) phage to unsensitized bacteria, which may be regarded as indifferent adsorbents. These adsorptions are reversible, in contrast to the specific adsorption. No evidence is obtained, therefore, that sensitization makes antigens sticky; and these experiments do not support the view that some mechanism of aggregation auxiliary to lattice formation operates in the systems tested (phage, serum proteins, type III pneumococcal polysaccharide, E. coli, Brucella).

We conclude that the aggregative stage of immune reactions is primarily a reaction between the immuno-specific valences responsible for the initial combination of antibody and antigen, in accord with the hypothesis of Marrack, and Heidelberger and Kendall.
Immunochemical Studies on Human Serum
Authors: Seifter S. , Pillemer L. , Ecker E. E.
Published: January 2023

Whole complement is preserved for at least one year by freezing and storage at −35 C with about one–third loss in activity. The addition of 10 per cent solid NaCl together with 4 per cent solid boric acid decreases the loss in activity. The precipitate which separates when human serum is dialyzed against phosphate buffer of pH = 5.4 and μ 0.02 is best preserved at 1 C in 5:1 concentration in pH = 6.6 phosphate buffer of ionic strength 0.3. The “pH = 5.4—μ 0.02 supernate” is best preserved at 1 C in 1:1.2 dilution in isotonic saline solution, or in 1:2.5 dilution in phosphate buffer of pH = 6.6 and ionic strength 0.3. For periods longer than 2 months it is best preserved by drying from the frozen state. Both the “pH = 5.4—μ 0.02 precipitate” and supernate may be passed through a micro-Seitz filter without impairment of their component activity. C′2 is that component of whole serum and of the supernate which is most susceptible to heat. C′4 is the most heat-susceptible component in the “pH = 5.4—μ 0.02 precipitate,” and the least heat-susceptible component in the “pH = 5.4—μ 0.02 supernate.” C′4 is the most susceptible component to pH changes in both supernate and precipitate, being most stable at pH between 6.0 and 6.8. C′3 and C′4 are those components of whole complement most susceptible to destruction upon standing under various conditions of temperature and dilution. The fact that C′4 is the least stable of the components in the “pH = 5.4—μ 0.02 precipitate,” as evidenced by its greater susceptibility to aging, pH variation, and heat, would indicate that the precipitate lacks certain protective substances which enhance the greater heat stability of C′4 in whole serum and in the “pH = 5.4—μ 0.02 supernate,” as well as the greater resistance of C′4 in whole serum to alkali. However, as yet there is no experimental evidence to warrant the conclusion that C′2 is the component necessary for the stabilization of C′4, or is the “carrier” component of C′4, as was concluded in the case of guinea-pig complement (4).
Pathogenicity, Antigenic Relationships and Evolutionary Trends of Shigella Alkalescens
Authors: Stuart C. A. , Rustigian Robert , Zimmerman Alice , Corrigan Francis V.
Published: January 2023

From a small population in a restricted area an almost perfect biochemically intergrading series of cultures from Shigella alkalescens to Escherichia coli were isolated which were antigenically identical or closely related. There is some evidence indicating that Shigella alkalescens and antigenically related cultures may have caused an epidemic of gastroenteritis in infants in the nursery of a general hospital. One hundred and forty-one biochemically typical Shigella alkalescens strains and 42 cultures intergrading biochemically from Shigella alkalescens to Escherichia coli possessed somatic antigenic fractions ABCD, ABCDE or ABCE. Major antigen A appears to be a Shigella alkalescens species specific antigen, major antigen B was found in paracolon and coliform bacteria, minor antigen C occurred in Shigella paradysenteriae, paracolon and coliform cultures and minor antigens D and E were found in paracolon and coliform bacteria. One or more untyped minor antigens were found common to Shigella alkalescens and paradysenteriae but not to paracolon or coliform bacteria.
An Alum Toxoid Prepared from Diphtherial Toxin Produced on a Gelatin-Hydrolysate Medium
Authors: Elias William
Published: January 2023

The literature on the concentration and purification of diphtherial toxin and toxoid, as reviewed by Smith (1932), and Leonard and Holm (1933), shows a long list of agents that have been used for these purposes. Both publications agreed that the best yields as well as superior immunizing values were obtained with toxoids precipitated with alum.

Roux and Yersin (1889) used aluminum salts to precipitate toxin from solution. However, the enhanced antigenicity of alum toxoid was first demonstrated by Glenny, Pope, Waddington and Wallace (1926), who showed that unwashed and undissolved alum-precipitated diphtherial toxoid was superior to crude toxoid in the immunization of guinea-pigs and rabbits.

Glenny and Barr (1931), and Wells, Graham and Havens (1932), found that the optimal amount of alum required for complete precipitation, with the least amount of extraneous material in the precipitate, differed with the various types of media used in the production of the toxin.
The Action of Penicillin on the Staphylococcus in Vitro
Authors: Rantz Lowell A. , Kirby William M. M. , Elizabeth Randall
Published: January 2023

Summary and Conclusions

The action of penicillin on staphylococci has been studied in vitro by photoelectric turbidimetric methods. Penicillin is bactericidal for the staphylococcus and causes lysis of the organism. There is a close correlation between the concentration of penicillin and its activity. The number of organisms in the initial inoculum appears to affect the activity of penicillin but the constituents of the culture medium do not. More than one hundred-fold variations in the sensitivity of strains of staphylococci to penicillin have been demonstrated.
The Complement-Fixation Reaction with the Antigen of Lymphogranuloma Venereum (Lygranum)
Authors: Blair John E. , Hallman Frances A.
Published: January 2023

In a series of complement-fixation tests with the antigen of lymphogranuloma venereum (lygranum) on 800 sera from 744 patients, four-plus fixation was obtained with 28.5 per cent of sera from individuals with known histories of venereal exposure, and with 8.5 per cent of sera from persons who were presumably not exposed. When Frei tests were done on patients whose sera gave complete fixation, about one-third were positive, giving reactions at least 6 mm in diameter. The significance of the complement-fixation reaction is discussed.
The Relation of the Rate of Absorption of Antigen to the Production of Immunity
Authors: Cook Marjorie W.
Published: January 2023

Studies of the rate of antigen absorption in sensitized and immunized animals, as contrasted with the rate of absorption in normal animals, have shown that previous treatment with an antigen confers upon an animal an increased power of absorption for that antigen. This fact was established with respect to sensitized rabbits and guinea-pigs by Doerr and Pick (1), Friedberger and Lurà (2), Römer and Viereck (3), and others. Smith and Cook (4) confirmed the work of Doerr and Pick and further (5) demonstrated that absorption of antigen in immunized animals proceeds much more rapidly than in sensitized or normal animals.

As it is evident that upon sensitization and particularly upon immunization, an animal acquires increased powers of absorption for the specific antigen, the question arises as to whether the process of immunity production is in any way dependent upon the changed absorptive powers of the organism.
A Study of Different Methods for the Preparation of B. Typhosus Antigen
Authors: Matsumoto Motomatsu
Published: January 2023

One of the reasons generally assigned for the unsatisfactory status of complement-fixation tests in the diagnosis of bacterial infections, is the difficulty of preparing efficient and stable antigens; among the diseases of bacterial origin complement-fixation is probably most widely employed in the diagnosis of glanders, tuberculosis and gonococcus infections, but in the last mentioned the test is well known as lacking in the sufficient delicacy and it probably can be rendered more sensitive by further improvement of the antigen, and the same may be true of the tuberculosis complement-fixation test.

Bacterial antigens for complement-fixation tests may be divided into four main groups, namely (a) those composed of whole bacteria and their soluble products in the fluid medium in which they have been cultivated; (b) those in which the bacterial cells alone are utilized suspended in sterile salt solution; (c) those in which the bacterial cells are disrupted but not filtered and (d) those in which the cells are disrupted and the insoluble portions removed by filtration, the filtrate being employed as antigen.
The Protective Value of Pneumococcus Vaccination in Mice and Rabbits
Authors: Wadsworth Augustus B.
Published: January 2023

Although the fact is well known that inoculation of animals with the pneumococcus develops against subsequent inoculation with virulent cultures an immunity which is specific for the homologous type of pneumococcus, there is no record of a quantitative determination of the degree of immunity that is obtained after vaccination with standardized vaccine. Accordingly a series of experiments with the inoculation of mice with pneumococcus vaccines of types I, II, and III were made, the results of which it is the purpose of this paper to record.

Miss Thelma L. Franklin, of the laboratory staff, prepared vaccines of pneumococcus types I, II, and III according to the standard methods used in the laboratory and vaccinated mice with these vaccines. In order to test the protection obtained as a result of the vaccination, living, virulent cultures were inoculated seven days after the last dose of the vaccine.
In Vitro and in Vivo Activity of Synthetic Detergents against Influenza a Virus
Authors: Klein Morton , Stevens David A.
Published: January 2023

Twenty compounds, including 18 cationic, anionic, and un-ionized detergents and two commercial compounds were tested for their activity against influenza A virus. Seven of the detergents and hexylresorcinol were found to be active in vitro in high dilution against influenza virus. However, none of the compounds when administered intranasally by instillation or spray protected mice against infection with influenza A virus. Immune serum against influenza A virus was the only agent found which effectively protected mice against infection.
The Negative Phase in the Antigonadotrophic and Precipitin-Productive Activities in Rabbits
Authors: Wolfe Harold R. , Meyer Roland K. , McShan W. H.
Published: January 2023

An antigonadotrophic substance has been produced in rabbits against the gonadotrophic activity in extracts of sheep pituitary glands. Intravenous injection of a pituitary gonadotrophic preparation into rabbits which have an antigonadotrophic substance in their sera, causes a marked but temporary decrease (negative phase) in the precipitin-producing and antigonadotrophic activities. Intravenous injections of sheep serum produced the negative phase in the serum precipitin but not in the antigonadotrophic substance. The negative phase lasted for about 48 hours after which the antibodies rapidly increased in quantity.
Production of Tetanal Toxin
Authors: Mueller J. Howard , Miller Pauline A.
Published: January 2023

A variant of a standard strain of Cl. tetani has been obtained which is capable of producing an unusually high titer of toxin in the presence of high levels of iron on a medium composed mainly of hog-stomach autolysate and beef-heart infusion. This toxin can readily be converted to toxoid with formalin, and the toxoid is antigenic for mice roughly in proportion to its test-dose. Somewhat less potent toxoid prepared on an almost identical medium has for some time been used for human immunization without producing untoward reactions (4). One may therefore assume that there should be no drawback in the use of the more potent material beyond that theoretically inherent in the use of enzymic digests generally. The high level of antigenicity should render such toxoid admirably suited to use in conjunction with gas-gangrene or diphtheric toxoid, since it could be diluted out ten times or more and still remain equivalent to commercial toxoids now being distributed.

Both the toxin here described, and the toxoid prepared from it flocculate sharply and rapidly with tetanal antitoxin, the former at approximately the neutral point. The reaction is entirely comparable with that of potent diphtheric toxin. The toxin should consequently be of considerable value in making possible the rough appraisal of antitoxic horse-sera during the course of immunization.

The ultimate objective of this work is to produce an equally potent toxin on a chemically defined medium. This may well prove to be a difficult matter and will certainly not be quickly accomplished. In the meantime it is hoped that the possibilities of this remarkably powerful toxin will give the work some immediate practical value. The strain of Cl. tetani is, of course, available to any laboratory.
Reduced Acute Toxicity of Antigens in Saline-in-Mineral-Oil Emulsion
Authors: Halbert Seymour P. , Smolens Joseph , Mudd Stuart
Published: January 2023

The acute lethal toxicity of Shiga neurotoxin, tetanus toxin, botulinus toxin, ricin and Flexner paradysentery somatic antigen for mice, is materially reduced by the administration of these agents in a saline-in-mineral-oil emulsion. The possible significance of this method of preparing vaccine for immunization procedures is discussed.
The Type-Specificity of Immune Protection Against Shigella Paradysenteriae (Flexner)
Authors: Weil A. J. , Farsetta K.
Published: January 2023

Experiments on passive protection of the chick embryo and active immunization of the mouse demonstrate the predominance of the type characterizing (“primary”) antigens of the Flexner bacillus in the immunological response of the host. Cooper's recent data show that this is also true for man.
The Role of Ether Anesthesia in the Production of Influenza Virus Pneumonia in Mice
Authors: Dubin I. N.
Published: January 2023

Swine influenza virus pneumonia of equal extent was produced in two groups of mice, one group having been anesthetized with ether and the other with nembutal administered intraperitoneally. This suggests that the insusceptibility of unanesthetized animals to influenza virus is to be explained merely on the basis of their failure to aspirate the virus. The ease with which viral pneumonia is produced in animals under ether anesthesia is to be referred to the ready aspiration of the viral suspension by the unconscious animals rather than to an increased susceptibility of the respiratory mucosa produced by ether.
Factors Influencing Leukoagglutination by Antileukocytic Sera
Authors: Steinberg Bernhard , Martin Ruth A.
Published: January 2023

A rapid procedure for leukoagglutination by specific antisera and conditions which influence it are presented. The procedure consists in suspending leukocytes in a small volume of saline, counting the cells with pipette and chamber and measuring out 27,000 cells per mm3 in 0.05 ml of normal saline. To the cells is added 0.5 ml of antiserum diluted with normal saline. The cell-antiserum mixture is centrifuged for one minute and the results are read. The entire procedure is carried out at 22 to 26 C.

Agglutination of leukocytes is inhibited at 8 C and the velocity is reduced at 37 C. The optimal temperature is 22 to 26 C. Centrifuging results in the greatest speed of antigen-antibody reaction. Immature leukocytes and especially those outside the body for 2 to 3 days are destroyed more readily than mature cells by hypotonic salt solution. Agglutination requires the presence of intact cells. Electrolytes are necessary for the visible phase of agglutination and the optimal range is 0.85 to 2.5 per cent. Mature leukocytes are agglutinated in lower concentrations. Ageing of cells outside the body interferes with agglutination and mature leukocytes are agglutinated up to the fourteenth day. Immature cells show little or no clumping after the fourth day. Repeated washing of leukocytes does not interfere with agglutination until after the tenth time when most of the cells are destroyed. Hemoglobin up to 50 per cent does not interfere with agglutination. A definite number of leukocytes is necessary for a satisfactory agglutination. Excess or decrease in the number of cells modifies the degree of clumping.
The Standardization of the Cardiolipin-Lecithin-Cholesterol Antigen in the Precipitation Test for Syphilis
Authors: Brown Rachel
Published: January 2023

Summary and Conclusions

Suspensions prepared from cardiolipin, alone or mixed with cholesterol, did not give any precipitation with reacting syphilitic human and rabbit sera. Suspensions prepared from lecithin alone or mixed with cholesterol gave only slight degrees of precipitation with reacting and nonreacting sera.

In tests with pooled reacting human sera diluted in 0.85-per cent sodium chloride solution, suspensions prepared from mixtures of lecithin and cardiolipin showed marked precipitating activity, maximal when the lecithin:cardiolipin ratios ranged from 10:1 to 25:1 and the concentration of the total lipids was from 0.24 to 0.39 per cent. The addition of cholesterol to the lecithin and cardiolipin in the same range increased the reactivity approximately 2-fold. The optimal cholesterol:lecithin ratio was sharply defined as 0.33:1 and the concentration of the total lipids was from 0.415 to 0.63. Within the range of 10:1 to 25:1 ratios of lecithin:cardiolipin, the reactivity was dependent upon the concentration of total lipids whether cholesterol was present or not. Antigen-suspensions of like concentration and of very similar precipitating activities could be prepared from stock alcoholic solutions of different total lipid concentrations if the final proportions of alcohol and sodium chloride solution were maintained constant. In all of the experiments, certain quantitative relations between serum and antigen were demonstrated.

In tests with undiluted reacting sera the optimal proportion of lecithin and cardiolipin was more sharply defined. A ratio of 25:1 and a cholesterol:lecithin ratio of 0.33:1 and a total lipid concentration of 1.03 per cent appeared to be optimal. Such a mixture was less subject to the phenomena of serum prozone reactions and inhibition of precipitation than other mixtures that were tested.
A Comparison of Rabbit and Mouse Antisera to Shigella Paradysenteriae
Authors: Doak Beatrice W. , Halbert Seymour P. , Smolens Joseph , Mudd Stuart
Published: January 2023

Agglutinin-titers against the same strains of S. paradysenteriae are higher in rabbit than in mouse antisera. High precipitin and mouse-protective titers are reached in rabbit sera, but they are negligible or low in mouse antisera. Mouse antisera obtained by us against the strains of S. paradysenteriae are more type specific than the corresponding rabbit immune sera.
Infection of Rats with the Virus of Influenza
Authors: Harford Carl G. , Smith Mary Ruth , McLeod Charlotte , Wood W. Barry
Published: January 2023

Intrabronchial inoculation of rats with heavy suspensions of pulmonary tissues of mice infected with influenza virus produced macroscopic lesions localized to the site of inoculation. When the suspensions were mixed with antiviral serum, the lesion was specifically inhibited. Multiplication of virus in the lungs of rats was indicated by the survival of influenza virus through eleven serial passages The microscopic lesions were noteworthy for the absence of significant changes in the bronchiolar epithelium.
The Production of Typhoid Antibodies in Rabbits with the Use of Living Typhoid Organisms Adsorbed on Aluminium Cream
Authors: Mann Lawrence S. , Spinka Isadore M.
Published: January 2023

In the preparation of antiserums for bacterial organisms one difficulty lies in the preparation of an effective antigen. If the organism is killed by heat or by chemical means, the native protein is partially or completely denatured. The resultant antiserum is usually not a straight antiserum for the characteristic protein of the bacterial organism. We have found that live organisms can be quantitatively adsorbed on aluminium cream and that when so adsorbed can be injected intramuscularly into animals without producing any deleterious effects, even when these organisms are pathogenic for the animal injected.

Procedure. Typhoid organisms isolated from an epidemic strain (Manteno) were grown on agar in Kolle flasks at 37 C. for 48 to 72 hours. The bacteria were washed from the agar with the smallest possible volume of sterile 0.85 per cent salt solution. The resultant suspension contained over 3 billion organisms per ml.
Salmonella Infections in the U. S. A.
Authors: Seligmann Erich , Saphra Ivan , Wassermann Michael
Published: January 2023

Among 1916 Salmonella cultures of human origin (excluding S. typhi) we found 46 different types occurring in this country. Together with those identified in a previous series of 1000 cultures the total of types identified in our laboratory is 53. The type distribution conforms to that previously reported: preponderance of S. typhi murium followed by S. paratyphi B and members of the C group next. Some variations in incidence, f.i. increase of SS. newport, oranienburg, anatum, panama, slight decrease of S. cholerae suis, are of minor importance. Clinical manifestations run the gamut from mild or severe gastroenteritis to septicemia and typhoidal forms or localized inflammatory processes. The outstanding invasiveness of S. cholerae suis was confirmed. There was an overall case fatality of 5.1%; that of S. cholerae suis infections was as high as 26%. The number of healthy carriers in the civilian population, especially those at large, was cosiderable: 19.5% of all stool cultures submitted. Children are dominantly involved in Salmonella infections; of 1497 studied civilian cases 40% were children under 10 years of age, 17% were infants. A pooled O-antiserum is recommended for the screening of suspected cultures. Ours covered more than 99% of all examined cultures. Problems of classification of the enteric group of bacteria have been discussed. Our findings suggest the need for a revision of the methods of control of Salmonellosis.
A Coliform Bacterium with the Complete Antigens of Salmonella Newington
Authors: Seligmann Erich , Saphra Ivan
Published: January 2023

A coliform organism has been found with the antigen mosaic of a typical Salmonella. The culture #2922 was sent to us by Miss Janie Morris of Atlanta, Ga., because of its puzzling reactions with certain Salmonella antisera. According to the attending physician the organism has been isolated from the spinal fluid of a 6 month old baby. The child was born with a spina bifida which had granulated over at seven days. It developed several attacks of meningitis which finally terminated in death. The stools were always green, loose, and very irritating to the skin.1

The culture consisted of motile, gram negative rods. It grew on Endo agar dark red with metallic sheen, produced red colonies on SS agar and turned triple sugar agar yellow (butt and slant) with gas formation. Lactose, dextrose, mannite, maltose, sorbitol, d-tartrate, dulcitol, rhamnose, arabinose, trehalose were promptly fermented.
The Preparation and Properties of a Purified Equine Encephalomyelitis Vaccine
Authors: Randall Raymond , Mills John W. , Engel Lewis L.
Published: January 2023

Purified vaccines of chick-embryo origin effective against the three types of equine encephalomyelitis virus known to occur in the Western Hemisphere have been prepared by a two stage differential centrifugation process.

All three types of vaccine confer upon guinea-pigs active immunity against the homologous type of virus even when it is injected directly into the brain. Moreover, antibodies neutralizing the Eastern type virus have been demonstrated in the sera of guinea-pigs following the administration of Eastern type vaccine and in the sera of human subjects following the injection of a mixture of Eastern and Western types of vaccine.

The purified vaccines are also characterized by a content of chicken- and egg-proteins significantly lower than that of the crude vaccine used for the immunization of horses and mules, and of commercial human-type vaccine.
The Relationship of Sulfhydryl and Disulfide Groups to the Antigenic Power of Bovine Serum Albumin
Authors: Williams Robert R.
Published: January 2023

Summary and Conclusions

Bovine serum albumin has been treated with several reagents which chemically alter the sulfhydryl and disulfide groups, although other effects have not been excluded. With the alteration of these groups by each of the methods described below, bovine serum albumin loses its antigenic power as measured by its capacity to produce anaphylaxis in guinea-pigs. The sulfhydryl and disulfide groups of bovine serum albumin have been oxidized with iodine to yield products containing no detectable disulfide groups. These products behave like the disulfoxide of cystine in that they undergo dismutation in neutral solution with formation of disulfides. Condensation of electrolytically reduced bovine serum albumin with pyruvic acid yields a product which gives no nitro-prusside test in guanidine solutions, but does give a strong reaction after treatment with alkaline cyanide. Oxidation of the above condensation product with hydrogen peroxide oxidizes the sulfur to a group which is stable to alkaline cyanide, possibly a sulfone. The oxidized condensation product is more soluble and more completely despeciated than the oxidation products obtained with iodine. It does not undergo the dismutation shown by iodine or peroxide-oxidized albumin in neutral aqueous solution.
Further Study of the Quantitative Complement-Fixation Test As Applied to the Serum Diagnosis of Typhus Fever
Authors: Varley Florence M. , Weedon Frederick R.
Published: January 2023

Summary and Conclusions

Eight extracts from strains of rickettsia causing epidemic typhus and 4 extracts from strains causing endemic typhus have been investigated together with 5 antisera from guinea pigs immunized against the former group and 2 against the latter group. The titer of any given serum was a function of the antigen against which it was tested. Titers found were reproducible. No conclusions regarding “types” of rickettsia can be drawn. Clear antigenic differentiation of epidemic versus endemic typhus was not demonstrated. Dilutions of antigen found to be optimal for differing amounts of one antiserum were found also to be optimal for appropriate amounts of all. Standardization of very large batches of antigen would be desirable for diagnostic and comparative purposes.