bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological Tests with Amino Acids
Authors: van der Scheer J. , Landsteiner K.
Published: January 2023

In the course of studies on the immunological specificity of peptides (1, 2) it was found necessary to establish to what extent amino acids which are contained in proteins can be differentiated by immune sera.1

Preparation of Para-Nitro- and Para-Aminobenzoyl Derivatives of Amino Acids. Nitrobenzoylation of the amino acids was mostly carried out by the method used previously for the preparation of p-nitrobenzoyl peptides (2). In the case of histidine a dilute solution of sodium hydroxide was used instead of sodium bicarbonate (3). Phenylalanine and tryptophane were dissolved in a small amount of normal sodium hydroxide before adding sodium bicarbonate. For the nitrobenzoylation of glutamic and aspartic acid the directions given by E. Fischer for the preparation of the benzoyl derivatives were followed (4). The products were freed from nitrobenzoic acid by extraction with ether, and if the nitrobenzoyl amino acid was appreciably soluble in ether, the ether solution was concentrated to a small volume and the substance precipitated by addition of petroleum ether (boiling point 90 to 100°).
A Study of Inactivated Yellow Fever Virus As an Immunizing Agent
Authors: Gordon John E. , Hughes Thomas P.
Published: January 2023

The injection of yellow fever virus fixed for mice together with immune serum (1) is an effective method of immunization against yellow fever but cannot be applied widely because of the difficulty in securing adequate amounts of immune human serum. The substitution of hyperimmune sera of animal origin has been suggested by Pettit and Stefanopoulo (2) and the feasibility of that procedure has been studied by Theiler and Whitman (3). Simplification in yellow fever immunization has been accomplished by the procedure of Sellards and Laigret (4), later modified by Laigret (5) in which active but allegedly attenuated virus is used without serum. The safety of this process has been questioned by Theiler and Whitman (6) and its efficiency by Findlay (7).

Immunization against dog distemper (8) and Rift Valley fever (9) by the use of inactivated viruses has revived interest in the application of this method to yellow fever immunization, although the results of previous investigations were unfavorable (1, 2, 10, 11, 12, 13).
The Plasma Lipids in Purpura Produced with Antiplatelet Serum
Authors: Tocantins L. M. , Cantarow A.
Published: January 2023

The following changes occur in the plasma lipids of dogs with thrombopenic purpura produced experimentally by the injection of a moderate dose of antiplatelet serum: the fatty acids show an immediate slight decrease followed by a marked increase, one to two days later, with a subsequent return to normal; there is an immediate increase in lipid phosphorus that persists for 3 to 8 days; the cholesterol shows no significant changes.
A Procedure for the Serological Determination of Blood-Relationship of Ancient and Modern Peoples with Special Reference to the American Indians
Authors: Matson G. Albin , Brady E. O.
Published: January 2023

Summary and Conclusions

An examination of saliva from individuals of the various blood-groups served to emphasize the fact observed by others that the antigens are not demonstrable in the saliva of all persons. It was found that group-antigens in saliva are present in the secretion itself and their occurrence there is not determined by the presence of epithelial cells or blood. The experiments indicate clearly that although the group-ferments in saliva may under suitable conditions destroy the antigens, they are not the only factors determining the absence of A or B substance in saliva. In a study of families it was found that the presence or absence of group-antigen in saliva presented no exception to the Mendelian laws of inheritance.
The Significance of Age of Rabbits for the Elicitation of the Shwartzman Phenomenon
Authors: Witebsky Ernst , Neter Erwin
Published: January 2023

A small percentage of adult rabbits is refractory towards the elicitation of the Shwartzman phenomenon. There is a definite relationship between the type and amount of toxin employed and the percentage of positive reactions. Shwartzman (1) reported that about 30 per cent of rabbits are refractory if typhoid agar-washing filtrate is used and only a few per cent with meningococcus agar-washing filtrate. It seemed of interest to determine whether constitutional factors, such as age, may play a rôle in the Shwartzman phenomenon. One litter of a few days old rabbits did not display the Shwartzman phenomenon in an experiment carried out by Gratia and Linz (2). Freund and Hosmer (3) observed that the appearance of the hemorrhagic local skin reaction depends upon the age and weight of the rabbits tested. A positive reaction was obtained in young rabbits weighing between 1100 and 2000 grams only after the reinjection of the bacterial agar-washing filtrate, but not after the reinjection of starch.
The Reaction of the Nursling Rabbit to Vaccination with Vaccine Virus
Authors: Pearce Louise , Hu C. K. , Rosahn Paul D.
Published: January 2023

Summary and Conclusions

The results of the vaccination with vaccine virus of 1185 nurslings in a rabbit breeding colony are reported. Failure to develop a local reaction to vaccination was of frequent occurrence, especially in very young rabbits. A characteristic finding in many animals was the occurrence of generalized manifestations, the most striking of which was a cutaneous papular eruption.

Vaccination was carried out in three successive experiments on December 19, 1933, January 24, and March 21, 1934. The general character of the resulting vaccinia underwent a progressive decline in severity, and in the last experiment there was little clinical evidence of infection.

The results are discussed from the standpoint of the reaction of the host and particularly with reference to such factors as the nature of the local response to vaccination, the age of the animal, the condition of fostering, and the immune or susceptible state of the nursing female.
The Complement Fixation Reaction in Experimental Equine Encephalomyelitis, Lymphocytic Choriomeningitis and the St. Louis Type of Encephalitis
Authors: Howitt Beatrice F.
Published: January 2023

The complement fixation test may be applied to the differentiation of the viruses of equine encephalomyelitis, lymphocytic choriomeningitis and St. Louis type of human encephalitis, respectively. The eastern, western and Moscow 2 strains of equine encephalomyelitis were clearly differentiated when using guinea pig brain antigens, but there was occasional cross fixation between the American strains when using mouse brain antigen. The Russian strain was quite distinct from either. There was no cross fixation between serums and antigens of the equine encephalomyelitic group and those of normal guinea pig and normal mouse or with the viruses of Borna disease, of lymphocytic choriomeningitis and of the St. Louis human encephalitis, respectively. Similarly there were no cross reactions between the antigens and serums of the 2 latter viruses nor between these and normal guinea pig brain antigens and serums, respectively. Complement fixing antibodies when once developed in hyperimmunized animals for the equine viruses may be retained for at least 3 months. The titer may decline but can be restored by virus injections. They may also be present in serums kept for at least 1 year and 10 months in the icebox. Neutralizing substances for the equine strains usually appeared somewhat earlier than the complement fixing antibodies. Antigens of the eastern, western and Moscow 2 strains of virus, respectively, gave positive fixation when passed through ultrafilters of 470 mu porosity. Potency was reduced by filtration through 200 mu membranes and entirely lost by those of 160 mu. Heating to 55°C. destroyed the antigenicity of the unfiltered western antigens and partially affected those of the eastern and Russian strains of equine encephalomyelitis. Heated filtrates were negative. The unfiltered mouse brain antigens of the American strains and those filtered through 470 mu gradocol membranes remained viable to mice, but not if heated or passed through finer filters. The Moscow 2 antigen remained viable only if untreated by heat or filtration.
Serological Variants of Pneumococcus Types 9 and 10
Authors: Vammen B.
Published: January 2023

Agglutinative and absorptive tests have revealed three serological type 9 variants (subgroups) and two type 10 variants. Comparative mouse-protective tests showed conformity with the antigenic structures found.
The Effect of Temperature Upon Combination and Aggregation and Upon Equilibrium in the Reaction Between Antigen and Antibody
Authors: Follensby Edna M. , Hooker Sanford B. , Leach Elizabeth T.
Published: January 2023

According to a current theory, reaction between antigen and antibody occurs in two stages. It is thought that specific combination takes place during the first stage and is followed by the secondary reaction of aggregation, considered specific by some investigators and non-specific by others. The second stage has been more thoroughly studied than the first. There are, in fact, few systems in which combination can be easily studied apart from aggregation; consequently we know little about the relationship between the two stages, whether the reactions proceed at the same rate and are similarly affected by such factors as temperature and concentration. The reaction between diphtheric toxin and antitoxin is one in which both combination and aggregation can be investigated. Glenny (14) has said of this system “… the appearance of visible flocculation may not be a simple function of the rate of preliminary combination of toxin with antitoxin, presumed to be loose, and this may bear no simple relation to the rate of ultimate combination, which is assumed to be of a firmer nature.”
Demonstration by the Electron Microscope of the Combination of Antibodies with Flagellar and Somatic Antigens
Authors: Mudd Stuart , Anderson Thomas F.
Published: January 2023

The electron microscope, by extending resolving power to a present practical limit of about 50 Ångstrom units (1, 2), is affording the opportunity for investigation of structures hitherto inaccessible to direct examination.

The electron microscope is also opening up new possibilities of investigation of process and mechanism, as well as of structure. Recording by electron microscopy of the process of lysis by phage (3), of the interaction of virus molecules with colloidal gold particles (4), of intracellular reduction of tellurite ion (5), and of the combination of virus with antivirus molecules (6, 7), may be cited as cases in point.

The present study concerns the sensitization of flagellate typhoid and paratyphoid bacilli and of Bacillus subtilis with rabbit antisera. Alterations of the bacterial cell-wall and flagella by deposition of specific antibodies which combine with surface somatic and flagellar antigens have long been deduced from the behavior of sensitized bacteria in agglutination (8) and phagocytosis and from parallel alterations in cohesiveness, wetting properties and electrophoretic properties (9, 10).
Experimental Diphtheric Paralysis
Authors: Feiner Rose R.
Published: January 2023

Diphtheric paralysis in guinea pigs was produced by the intravenous injection of 0.1 to 0.4 mld of toxin alone. The ratio of the paralytic dose to the minimal lethal dose was the same with each of four toxins used, including a highly purified, a gravis, a mitis, and an intermediate toxin. In vitro contact of toxin with nerve tissues caused neither a loss in lethal nor in paralytic action of the toxin. The loss of ability of heat-, light-, formalin-, or H2O2-treated purified toxin to produce paralysis paralleled the loss of ability to produce cutaneous necrosis or death. The non-toxic supernates of neutral toxin-antitoxin mixtures did not produce paralysis. Tissues removed from paralyzed guinea pigs were not capable of inducing paralysis in normal guinea pigs. No local peripheral nerve immunity developed as a result of one attack of paralysis. Guinea pigs once recovered succumbed to the re-injection of paralyzing doses with no difference in length of incubationary period, duration, or severity, as compared with the first attack. The intraneural injection of toxin produced a mild paresis that appeared relatively soon after injection, but it did not resemble true diphtheric paralysis. There was no evidence of centripetal diffusion of toxin.
Studies on the Mechanism of Sulfonamide Bacteriostasis, Inhibition and Resistance
Authors: Strauss Elias , Dingle John H. , Finland Maxwell
Published: January 2023

A strain of E. coli was studied which, in a simple synthetic medium, required nicotinic acid or nicotinamide for growth from small inocula. Growth was also improved by increasing the concentration of carbon dioxide in the atmosphere.

Sulfathiazole, sulfadiazine, sulfapyridine, sulfaguanidine and sulfanilamide were bacteriostatic in relatively small concentrations, as compared with their activity against this organism in complex media.

Nicotinamide, nicotinic acid and coenzyme I did not inhibit the action of these sulfonamide drugs.

P-aminobenzoic acid is a strong inhibitor of sulfonamide action, methionine a weak inhibitor. Differences in the effect of methionine on various sulfonamide drugs may be quantitative rather than qualitative.

The development of resistance to sulfonamide action has been produced with E. coli in a simple medium. P-aminobenzoic acid prevents the development of sulfonamide resistance, while methionine delays but does not prevent the development of resistance.
The Influence of Iron on the Production of Diphtheria Toxin
Authors: Mueller J. Howard
Published: January 2023

The observation of Pappenheimer and Johnson that abundant formation of diphtherial toxin occurs only in a relatively narrow zone of concentration of iron has been thoroughly verified. It has not proved possible to shift or extend this zone by the addition of other inorganic or organic materials (except manganese salts which seem partially to take the place of iron). On the other hand, addition of relatively large quantities of iron does not completely prevent toxin-formation, but rather reduces it to a comparatively low level. It is suggested that such a level represents normal production, whereas the larger amount obtained under conditions of iron starvation is the result of a compensatory mechanism in which the iron-free toxin molecule takes part in some process which is ordinarily catalyzed by an iron-containing enzyme.
Toxin-Production As Related to the Clinical Severity of Diphtheria
Authors: Mueller J. Howard
Published: January 2023

C. diphtheriae elaborates relatively little toxin in the presence of concentrations of iron present in the throat. In the average case of mild diphtheria comparatively small amounts are probably formed. Severe (gravis) diphtheria may result from infection with strains able to produce more toxin in the presence of abundant iron. Three non-gravis types have been shown to produce approximately 3 MLD/ml under these conditions, whereas a gravis type produced 40 MLD. It is probable that a difference of this order is sufficient to explain observed variations in the clinical severity of the disease.
The Inhibition of the Bactericidal Power of Human and Animal Sera by Antigenic Substances Obtained from Organisms of the Typhoid-Salmonella Group
Authors: Cundiff Richard J. , Morgan Herbert R.
Published: January 2023

Sera with high titers of bactericidal antibody can be obtained in man and the rabbit by repeated intravenous injections of a purified somatic antigen of E. typhosa. The bactericidal activity of antityphoid immune sera prepared by injection of bacterial cells or the purified somatic antigen of E. typhosa is inhibited by the addition of the somatic antigen. The somatic antigens of S. enteritidis and S. paratyphi B show a similar but less marked effect which is in accord with the antigenic classification of White and Kauffmann. The specificity of this inhibition is further indicated by the failure of an extract of Friedländer's bacillus, type A to exert any effect on the bactericidal activity of the immune sera.
Potency-Determination of Antipertussis Serum by the Mouse-Protective Test
Authors: Holm August , Bunney William Edward
Published: January 2023

Reproducible results may be obtained by the procedure given for conducting the mouse-protective test with antipertussis serum.

This has made it possible to establish a provisional standard unit for use in the evaluation of antipertussis rabbit-serum by the mouse-protective test.

A provisional standard unit is defined as that amount of standard serum which will protect 50 per cent of the mice against 2 MLD of a virulent strain of H. pertussis suspended in 4 per cent gastric mucin.

Antipertussis rabbit-sera may be standardized in terms of a control serum using White's formula.

This method of conducting the mouse-protective test in the potency-determination of antipertussis sera is practical and assays specific protection in terms of provisional units.
Effect of Induced Hypercholesterolemia on Antibody-Nitrogen Production (Pneumococcus Type 2) in Rabbits
Authors: Member Samuel , Bruger Maurice , Ehrlich Sylvia B.
Published: January 2023

It is sometimes assumed that serum- or tissue-cholesterol is related in some fashion to the process of immunity. Borchardt (1) found that in cats the intravenous administration of colloidal cholesterol increased the resistance of the animals to Staphylococcus aureus infection. Recently, Chassin and Bruger (2) demonstrated that after the injections of typhoid vaccine, hypercholesterolemic rabbits showed a higher agglutinin titer against E. typhosa than control rabbits with normal blood-cholesterol. Member, Bruger and Chassin (3) found that the total and ester-cholesterol content of the blood was maintained at normal levels during the early stages of immunization of horses with pneumococci. In the later stages of immunization, however, a significant decrease in these sterols occurred.

In the present investigation rabbits were used. The experiments were devised to determine the effect of cholesterol-feeding upon antibody-nitrogen production in rabbits receiving large amounts of pneumococci.
A Large-Scale Serum-Neutralization Survey of Certain Vertebrates as Part of an Epidemiological Study of Encephalitis of the Western Equine and St. Louis Types
Authors: Hammon W. McD. , Lundy H. W. , Gray J. A. , Evans F. C. , Bang F. , Izumi E. M.
Published: January 2023

From an irrigated western valley region, where both St. Louis and western equine encephalitis occur in annual epidemics, 576 sera representing 74 species were examined by means of the neutralization-test for antibody against both viruses. Each of the viruses was neutralized by approximately 50 per cent of the sera from domestic fowl and to a less extent by sera from domestic mammals. The sera from wild species from each group showed a significantly lower percentage of positives than those from the respective domestic groups. Only 8 per cent of the sera from wild mammals possessed antibodies. No sampling error was found which would alter the significance of these differences. From “control” areas, where encephalitis was not recognized, 132 sera, largely from domestic species, were tested. Only one was positive. This confirms the specificity of the neutralization-test. In this valley the epidemiology of these two diseases appears to be parallel. It is concluded that many of these birds and mammals, principally the domestic fowl, probably serve as reservoirs for infection of mosquitoes. The percentage of susceptible horses which become infected is very high.
Antepartum Transmission of Lymphogranuloma Venereum Antibodies and Their Duration in the Infant
Authors: Levine Sonnia , Bullowa Jesse G. M. , Scheinblum Irving E.
Published: January 2023

Fifteen, or four and two-tenths percent, of two hundred and eighty antepartum women without signs or symptoms of lymphogranuloma venereum gave positive Frei reactions as well as complement fixation for lymphogranuloma venereum. The infants of ten positive Frei reactors were studied for complement fixation in their first week of life and again after 8 to 14 weeks. Correspondence between the titer of the complement fixation of the sera of mother and infant was found during the first week of life. After 8 to 14 weeks the infant's sera became negative. Only the antibodies for lymphogranuloma venereum were temporarily present in the infants of mothers with asymptomatic lymphogranuloma venereum.
Studies on the Immobilization-Reaction of Trichomonas Foetus (Protozoa) in Cattle
Authors: Morgan Banner Bill
Published: January 2023

Summary and Conclusions

Immune bodies were produced by the injection of cows with living or formalinkilled Trichomonas foetus. The degree of antibody-response was low, as determined by the test described above, and results indicate that T. foetus is not highly antigenic. In the sera of five heifers injected intramuscularly with washed motile trichomonads, 2 heifers with formalin-killed trichomonads, and 2 heifers intravenously with living trichomonads, immobilization of the microorganisms was observed in dilutions ranging from 1:4 to 1:128. Thus, there there was some degree of variation of titer among the cows. Inoculation with a single injection of trichomonads after a rest period of approximately 102 days produced titers as high as the previous maximal titer or higher. The average time for the agglutinins to appear after the first injection was 17 days, for maximal immobilization 55 days, for total duration of the agglutinins 177 days and duration of complete immobilization 40 days. No agglutinins were detected in the sera of 400 normal trichomonad-free cows and 52 normal trichomonad-free bulls. Also, this test failed to show agglutinins in 11 trichomonad-infected bulls. Sera from 51 cows divided into 3 groups according to the type of trichomonad-infection were tested. In 10 cows in which trichomonads were recovered from the vaginal tract all sera were negative. In 12 cows with early abortion produced by T. foetus, only 2 sera reacted, one with a complete immobilization at a dilution of 1:1, and one with a partial immobilization at the same dilution. In the 29 cows with trichomonad-pyometra only 2 sera reacted slightly, both with partial immobilization at a 1:1 dilution. On the data presented with 9 injected animals, 400 normal cows, 52 normal bulls, 11 infected bulls, and 51 infected cows, it appears that the immobilizationreaction cannot be successfully utilized as a means for the diagnosis of bovine trichomoniasis.
Group-Specific Substances in the Saliva of the New-Born
Authors: Wiener Alexander S. , Belkin Ruth B.
Published: January 2023

A series of thirty pairs of saliva-samples from mothers and their new-born infants were tested for their content of group-specific substances. It was found that the distinction between secretors and non-secretors was as sharp in the infants as in the mothers, indicating that this character is fully developed at birth and contradicting the report of Hartmann.
Prophylactic Immunization Against Carrión's Disease
Authors: Howe Calderon , Hertig Marshall
Published: January 2023

Summary and Conclusions

The incidence of infection with Bartonella bacilliformis, and of clinical Carrión's disease in non-immune military personnel stationed at three points in the verruga zone is estimated on the basis of observations made by one of the authors (M. H.) during an 18-month period preceding the present experiment. Preparation of formolized suspensions of B. bacilliformis, is described, these suspensions constituting the vaccine used herein. A group of 22 guards without previous history of Carrión's disease, thus presumably non-immune, were inoculated subcutaneously with 1 ml of formolized vaccine prior to being stationed in the verruga zone. Most of these guards received one or two more injections of vaccine during the first two weeks of their service. The majority were followed by the authors for the ensuing seven months, blood for cultures and serum being taken from each guard on several occasions during this period of observation. This subcutaneous inoculation of 22 humans with formolized suspensions of B. bacilliformis resulted in the appearance in their serum of a high titer of homologous agglutinins. From the blood of twelve, or 55 percent, of these, B. bacilliformis was cultured on one or more occasions during the period of observation following vaccination. Five out of the twelve developed a mild degree of verruga eruption. All twelve had shorter or longer periods of mild systemic symptoms. Only one required hospitalization, being the sole member of the whole group who was at all incapacitated. Comparison of these results with the observations made on unvaccinated guards during the 18 months preceding the present experiment warrants the belief that active immunization as here carried out, although not preventing infection, may definitely ameliorate the course of potentially serious Carrión's disease. The protective effect of the vaccine used is thought not to be directly related to the specific serum agglutinins which result from its administration. The exact mechanism of protection is not clear.
The Relation of the Dose of Antigen to the Degree of Anaphylactic Shock in Dogs
Authors: Dragstedt Carl A.
Published: January 2023

The term anaphylaxis means absence of protection and thus expresses recognition of the fact that the sensitivity of the animal is more important than the toxicity of the antigen in determining the occurrence of a reaction. This view is appreciated by every one when contrasting the behavior of sensitized animals with that of normal animals. It is not, however, so generally appreciated in comparing one sensitized animal with another. For example, there are many published reports in which investigators have studied the prophylactic effect of various agents by sensitizing a series of animals, ascertaining a “fatal dose” of antigen in a small group of control animals, and determining whether or not some of the treated animals could withstand a larger dose of antigen. The rationale of such experiments imputes a toxicity to the antigen, which should be expressed by a positive correlation between the severity of the anaphylactic reaction and the dose of the injected antigen, such as is the case for the lethal action of directly poisonous agents.
Attempts to Obtain Specific Agglutination of Mixtures of Collodion Particles or Bacterial Cells with Virus and Antiviral Serum
Authors: Pearson Harold E.
Published: January 2023

When collodion particles or bacterial cells were mixed with influenzal virus and then exposed to immune serum from man or ferret, specific flocculation was not observed although a variety of technics was employed. Nor was specific flocculation noted when the Lansing strain of poliomyelitic virus and serum from immune monkeys were studied under similar conditions.

Specific flocculation was not obtained when the bacterial-cell-agglutination (B.A.) method was employed in tests using the above-mentioned materials or in tests using sera from immune rabbits and the viruses of St. Louis encephalitis or eastern equine encephalitis.
Inactivation of Influenza Virus by Mild Antiseptics
Authors: Dunham Wolcott B. , MacNeal Ward J.
Published: January 2023

A number of antiseptics were tested for their inactivating effect upon the virus of influenza during a brief period of exposure. This was accomplished by preparing mixtures of the antiseptics and virus, allowing them to remain in contact for 3 minutes, diluting the mixtures to the point where they would not be toxic for chick embryos and then injecting the material into embryonated eggs. Survival of the embryos indicated inactivation of the virus.

The following preparations were found to inactivate the virus in 3 minutes or less: phenol, 3 per cent; tincture of iodine, U.S.P. XII, 0.1 per cent; Lugol's solution, U.S.P. XII, 1 per cent; mercuric chloride, 1:1000; potassium permanganate, 1:1000; copper sulfate, 1 per cent; propylene glycol, 90 per cent; liquor antisepticus, N.F. VII, 80 per cent.
Hemagglutination by Products of Influenzal Virus Using Infected Mouse-Lung and Chick-Embryo as the Source of Virus
Authors: Twyble Ellsworth , Mason Herman C.
Published: January 2023

Embryonic chick, one-day-old chick, adult chicken, duck, pigeon, turkey, guinea-pig and human erythrocytes may be agglutinated in the Hirst reaction while rabbit, rat, mouse and sheep are not. Chicken and duck cells have given the highest titers with infected allantoic fluid whereas pigeon and human have given the lowest. Infected mouse-lung may be used as the source of virus in either agglutinative or agglutination-inhibitive tests. The results parallel the use of allantoic fluid. Filtration removes much of the infectious agent by both mechanical blocking and adsorption. A rough estimate may be made of the degree of this adsorption of influenzal virus by the in vitro test. The extent of consolidation of the mouse-lung, pathogenicity for mice and agglutinative titer seem to be closely associated. Bacterial contamination of lungs does not destroy the agglutinating principle. The PR8 strain has been found by these means to be serologically related to the Alaska strain but does not appear related to the McCallum or PJP strains.
A Simplified Procedure for Titrating Hemagglutinating Capacity of Influenza-Virus and the Corresponding Antibody
Authors: Salk Jonas E.
Published: January 2023

A simplified procedure, based upon Hirst's test for titrating hemagglutinating capacity of influenza-virus and the corresponding antibody, has been described. The chief modifications involve reduction in the quantity of cells employed, determination of the endpoint of agglutination and inhibition by the pattern of the sedimented cells, and less rigid adherence to a specific time-interval.

The influences of temperature, time, concentration of erythrocytes and order of addition of reagents have been investigated.

The method has been standardized for optimal sensitivity and simple criteria have been adopted for measuring agglutination. The test for antibody-content of a serum has been simplified so as to reduce the amount of material required and by preparation of dilutions of serum directly in the suspension of red cells, thus involving the addition of one rather than two reagents to the serially diluted serum.

The desirability of adopting some uniform scale for expressing the titer of antihemagglutinins in a serum has been discussed.
Natural Antibodies Against Yeast-Like Fungi As Measured by Slide-Agglutination
Authors: Drake Charles H.
Published: January 2023

Summary and Conclusions

A survey was made of the natural agglutinins against five different yeast-like fungi in the sera of 114 humans and 52 rabbits. Of the rabbit sera, 81 per cent reacted with at least one organism. Saccharomyces cerevisiae was most frequently agglutinated to the highest titer (42 per cent of the sera). Of the human sera, 95 per cent reacted with at least one organism. Candida albicans was most frequently agglutinated to the highest titer (45 per cent of the sera). The pattern of my findings lends support to the theory according to which a considerable proportion of so-called natural antibodies represent normal serum constituents. This is indicated by the fact that the incidence of agglutinins appears to be independent of the likelihood of exposure to a given organism. The advantages of slide-agglutination as compared with tube-agglutination for “yeasts” are discussed.
Studies in Human Malaria
Authors: Heidelberger Michael , Mayer Manfred , Alving Alf S. , Craige Branch , Jones Ralph , Pullman Theodore N. , Whorton Merrill
Published: January 2023

Formalinized malaria vaccine, administered to man in relatively large quantity by various parenteral routes apparently was without serious toxicity. Local inflammatory reactions, chills and fever subsided with repeated administration. The administration of such vaccine in a dosage of 10 billion formalinized parasites per man over a period of 13–14 days had no effect on susceptibility to infection with malaria by the bite of vivax-infected mosquitoes.
The Effect of Nutritional Deficiencies on the Development of Neutralizing Antibodies and Associated Changes in Cerebral Resistance against the Virus of Western Equine Encephalomyelitis
Authors: Ruchman Isaac
Published: January 2023

The influence of underfeeding, deficiency of the whole “B” complex, thiamin-deficiency, riboflavin-deficiency, carbohydrate-deficiency and protein-deficiency was studied with respect to its effect on the development of immunity in mice vaccinated with formalinized Western equine encephalomyelitis mouse brain virus. Immunity was determined by the development of cerebral resistance and of neutralizing antibodies. The latter were quantitatively determined by the method of serum dilution as well as the usual method employing undiluted serum. Mice were given three doses of vaccine of 0.3 ml each intraperitoneally on three alternate days and were tested two weeks after the first dose.

Underfed mice developed considerable immunity but not to the same extent as did those on an adequate diet. The well-nourished vaccinated mice resisted between 100 and 200 times more virus intracerebrally than did the underfed animals. The test for neutralizing antibodies likewise showed a significant difference between undernourished and well-nourished mice, with the well-nourished animals neutralizing between 10 and 100 times as much virus as did the starved mice. The serum of the adequately nourished animals could be diluted between 3 and 8 times more than that of the serum obtained from the undernourished mice and still neutralize the effects of a constant amount of virus (50 LD50 doses). Prolonging the period of starvation for an additional two weeks did not accentuate the depressed immunity response. There was no difference in the immune response of animals on a synthetic diet and those on a stock diet. Removal of the whole “B” complex from the synthetic diet yielded equivocal results regarding the immune response in mice, but a decreased ability on the part of “B”-deficient animals to produce antibodies appeared possible. In one case the “B”-deficient animals developed a neutralization index which was 15 fold less than that of the control animals and no difference when the diluted serum was tested against a constant amount of virus and in the other case no difference between neutralization indexes occurred but this time the serum from adequately fed animals could be diluted six times more than that of the “B”-deficient animals and still neutralize the effects of a constant amount of virus. Thiamin- or riboflavin-deficiency had no effect either on the production of neutralizing antibodies or on the development of cerebral resistance. Protein- or carbohydrate-deficiency did not cause a marked failure on the part of deficient animals to develop immunity but there was a quantitative difference. The cerebral immunity was about ten fold greater in the well-nourished than in the deficient mice. The neutralization index of the serum from the well-nourished animals was twenty fold greater and the serum could be diluted three to four times more and still neutralize the effect of 50 LD50 doses of virus in mice.
Endotoxic Factors of Rickettsia Prowazeki and Their Immunological Relationship to the Endotoxins of Other Gram Negative Microorganisms
Authors: Olitzki L. , Czaczkes J. W. , Kuzenok A.
Published: January 2023

In a former publication Olitzki et al. (1) reported that rickettsial vaccines which have been heated for two hours at 100 C elicit endotoxin reactions such as are also produced by other gram negative microörganisms. Hypothermic reactions and decrease of the liver glycogen level are elicited in white rats both by rickettsial vaccine and by bacterial vaccine prepared from many other gram negative microorganisms and leucopenic effects are elicited in guinea pigs by the same agents. The purpose of the experiments described below was to ascertain whether there is an immunological relationship between the hypothermic and the liver glycogen lowering factors of R. prowazeki and those of certain other gram negative microörganisms. Special attention was paid in this connection to Proteus X19 in view of the well known antigenic relationship between Rickettsiae and this bacterium (Weil-Felix reaction).

Experimental. Technic. White rats weighing 25 g with rectal temperatures of 36.5–37.8 C were used.
Chemotherapy of Experimental Anthrax Infections
Authors: Miller Edward S. , Scott Earl B. , Noe Herbert A. , Madin Stewart H. , Henley Thomas F.
Published: January 2023

Streptomycin, penicillin and sodium sulfadiazine were tested for efficacy in experimental anthrax infections in mice. Maximal survival rates of 92 per cent were obtained with streptomycin, 58 per cent with penicillin, and only 5 per cent with sulfadiazine. Latent infections were not present in treated animals surviving 28 days after inoculation with lethal doses of B. anthracis spores.
Studies on Ragweed Pollen Sensitization in Rabbits and Guinea Pigs
Authors: Kulka Anna M. , Hirsch Dorothy
Published: January 2023

Summary and Conclusions

Rabbits were injected with ragweed-pollen-extract in water-in-oil emulsion containing killed tubercle bacilli, and observed over a period of two years. Repeated injections were found to produce more vigorous sensitization and antibody-formation than a single injection. Once a serum-antibody-level is reached which is characteristic for the animal it is usually maintained for six months without injection. Guinea-pigs injected with ragweed-pollen-extract with adjuvants were shown to develop antibodies capable of passively sensitizing normal human skin. These antibodies seem to be quantitatively unrelated to the collodion-agglutinative titer. No relation was observed between them and the degree of skin-sensitivity, nor to susceptibility to shock.
The Antigenic Relationships of Native Antigens of Species of Brucella
Authors: Silverman Sidney J. , Elberg Sanford S.
Published: January 2023

The serologic reactions between phenol-extracted antigens of Brucella and their antisera have been studied by the quantitative precipitin reactions. The curves of the amount of total nitrogen precipitated when plotted against the antigen nitrogen added showed a series of two or more maxima as the amount of antigen was increased. It was suggested that these secondary rises were indications of reactions between minor antigen-antibody systems. The absorption of anti-melitensis serum with a rough strain of either Br. abortus or Br. melitensis eliminated the secondary rises. Throughout the entire range of the reactions an antibody excess has been shown affording further evidence of the mixed nature of the antigens. The ratios, antibody nitrogen/antigen nitrogen, of the precipitates were lower for the suis system than with the other systems at the point of maximum precipitation. The similarity of the reaction curves and the ability of heterologous antigens to remove more precipitins from an antiserum than the homologous antigen, suggested a close relationship between the fractions obtained from the three species. This relationship may be an expression of a common group antigen such as that attributed to the rough component of the cell, or to other still unknown antigenic components. Although the course of the reactions reported here did not follow the linear relationship for pure systems as developed by Heidelberger and Kendall, it appeared that the homologous systems would show a linear relationship between precipitate ratios and antigen added for the first three and four points. Heterologous systems did not and would not be expected to do so.
The Action of Aureomycin and other Chemotherapeutic Agents in Experimental Brucellosis
Authors: Braude Abraham I. , Spink Wesley W.
Published: January 2023

Summary and Conclusions

A method is described for testing the action of drugs against the acute lethal effect of brucella in mice. Of the agents believed to be therapeutically effective in human brucellosis, aureomycin and a combination of streptomycin and sulfadiazine afforded mice excellent protection against the acute lethal effect of brucella. When chloramphenicol was given in the largest doses possible to administer by injection, there was only slight protection. Mice were protected against the acute lethal effect of brucella as late as 72 hours and possibly 96 hours after the last dose of aureomycin. The protective action of aureomycin against the acute lethal effect of brucella may be due to a primary antitoxic property. Aureomycin inhibited the multiplication of Brucella abortus in sublethal infections of mice and Br. suis in sublethal infections of guinea pigs. In a small minority of animals infected with Br. abortus, there was evidence that the infection was prevented after treatment with aureomycin. The action of aureomycin in experimental brucellosis has been compared with its action in brucellosis in man.
The Egg-White Inhibitor of Influenza Virus Hemagglutination
Authors: Lanni Frank , Lanni Yvonne Théry , Beard J. W.
Published: January 2023

Ten per cent solutions of egg-white, preserved with 0.25 per cent phenol, 0.02 per cent Merthiolate (Lilly), or 0.05 per cent formalin and stored at 4 C, were titrated periodically for inhibitory activity against hemagglutination by heated, purified swine influenza virus. No significant change in activity could be demonstrated over a period which exceeded 7 months for some of the preparations. Phenol proved more effective than Merthiolate or formalin in prohibiting the growth of micro-organisms and is, accordingly, preferred for preservation of standard solutions. Frozen samples of unpreserved egg-white and samples dried from the frozen state in vacuo gave irregular results. The high stability of the inhibitory activity of preserved solutions was confirmed by the experimental identity of the slopes of inhibition curves for aged and fresh samples of egg-white. The usefulness of slope as a criterion of degradation of the inhibitor is illustrated by results obtained when inhibitor is heated at 100 C or treated with crystalline chymotrypsin. With the aid of a standard solution it was found that the inhibitory activity is highly stable in semipurified preparations of inhibitor. Data are presented to illustrate the accuracy of the inhibition titrations, the variation of activity among individual egg-whites, and the essential absence of dependence of the inhibition titer on the individual source of the chicken red cells used in the tests.
The Influence of Polymorphonuclear Leukocytes and Macrophages on Antibody Production
Authors: Walsh Theodore E. , Smith Catherine A.
Published: January 2023

The site of production of antibodies and the cells active in their elaboration is still the subject of much controversy. Immunologists have long been interested in the role of macrophages in the production of antibodies. Since Metchnikoff (1) at the turn of the century demonstrated the production of antibodies by tissues rich in macrophages, much evidence has been accumulated substantiating his observation. The relation of active macrophages to immunity has been reported by Bieling and Isaac (2), Siegmund (3), Standenath (4), Gay and Clark (5), Jungeblut and Berlot (6), Ross (7), Cannon, Baer, Sullivan and Webster (8), Tuft (9), Phillipson (10) and others in their experiments in which the reticuloendothelial cells were “blockaded” by various substances. More recently it has been suggested that lymphocytes (11) and plasma cells (12, 13, 14) are more intimately associated with the actual production of antibody.

The part played by the polymorphonuclear leukocytes in the immunologic processes is less well understood.
The Serological Response of Cotton Rats and Monkeys to Poliomyelitis Virus
Authors: Pollard Morris
Published: January 2023

The serological response of cotton rats and monkeys to Lansing poliomyelitis virus was studied. A specific complement fixing antigen was prepared from cotton rat nerve tissues infected with Lansing strain poliomyelitis virus. In the course of immunization, cotton rats developed a rapid rise and decline of complement-fixing antibodies; however, the neutralizing antibody developed quickly and remained elevated. The antigen failed to demonstrate complement-fixing antibodies in immunized monkeys, although the latter animals developed neutralizing antibodies.
Protection of Mice Against the Vaccinia Virus by the Administration of Phenoxythiouracils
Authors: Thompson R. L. , Price Marian , Minton S. A. , Falco Elvira A. , Hitchings G. H.
Published: January 2023

Certain 5-phenoxythiouracils, although only moderately active inhibitors of vaccinia virus in chick embryonic tissue culture, have a significant protective effect in vivo. A reduction in the mortality of mice as a result of treatment could be demonstrated with the IHD strain inoculated intracerebrally and nasally and with the WR strain inoculated intracerebrally.

The protective effect of therapy could be demonstrated only when treatment was begun soon after infection was initiated. Treated animals appeared to have a lower titer of virus in the brain than untreated animals. These facts suggest that these substances directly or indirectly diminish the rate of viral multiplication without, however, having a virucidal action.

5-(2′4′-Dichlorophenoxy)-4-hydroxy-2-mercaptopyrimidine was found to be the most effective compound tested. This substance protected mice against the vaccinia virus when administered parenterally or in the diet. It shows no demonstrable antibacterial activity at concentrations which inhibit growth of the vaccinia virus nor has a protective effect against other viruses been demonstrated.
Antigen—Antibody Reactions in Agar
Authors: Becker E. L. , Munoz J. , Lapresle C. , Le Beau L. J.
Published: January 2023

A simplified description is given of the manner in which the precipitate in the Oudin tube is formed and moves. On the basis of this simplified picture and with the aid of certain stated assumptions the following limiting equation has been derived: (2) R′AB = AG0(1=2/πεy0e-y2dy) This equation relates R′, the ratio of antigen to antibody at the equivalence point, Ab, the antibody concentration, Ag0, the antigen concentration in the overlaying solution, x, the distance moved in time, t, and D, the diffusion coefficient of the antigen. The above question is a limiting equation applying only to high concentrations of antigen and low concentrations of antibody. From (2) another expression was obtained: which can be applied to the determination of the diffusion coefficient of an antigen present in a mixture. From (2) a third relationship was obtained: where DA is an apparent diffusion coefficient. This equation is of the same form as that which Oudin obtained empirically. Diffusion coefficients were calculated from data obtained for three different antigens using equations 2 and 3. Reasonably good agreement was obtained with the generally accepted values. The various assumptions used in the derivation of equation 2 were critically discussed. The possible uses and limitations of the three equations were briefly indicated.
Immunization of Laboratory Workers with Purified Trivalent Equine Encephalomyelitis Vaccine
Authors: Maurer Fred D. , Kuttler Kenneth L. , Yager Robert H. , Warner Albert
Published: January 2023

A partially purified trivalent vaccine of chick embryo origin was prepared and used to immunize laboratory personnel against Eastern, Western and Venezuelan strains of equine encephalomyelitis. Individuals who had not previously received equine encephalomyelitis vaccines were given 0.75 ml subcutaneously, while those who had received equine encephalomyelitis vaccines in the past were given a single booster of 0.1 ml intradermally or 0.75 ml subcutaneously. Antibody responses to annual booster immunizations were elicited satisfactorily when given by either the intradermal or subcutaneous routes of inoculation. The use of one intradermal trivalent booster to maintain immunity against these three diseases helps to simplify the immunization procedure.