bluuebunny/crossref_metadata_2025 huggingface dataset:
The Long Persistence of Rickettsia Orientalis in the Blood and Tissues of Infected Animals
Authors: Fox John P.
Published: January 2023

Summary and Discussion

The ready demonstration of R. orientalis in the blood and tissues (liver, brain, and kidney) of albino Swiss mice at intervals up to 610 days after infection has been reported. These mice survived in a few cases (not tested for virus beyond the 62nd day) because primary infection was by the subcutaneous route. For the most part, they survived because of treatment with toluidine blue or methylene blue. During this period the serum antibody (complement fixing) was high and the mice were resistant to reinfection. The greatest concentration of infectivity appeared to be in the kidney, and the least, perhaps because of the presence of antibody, in the blood. No infectivity was demonstrated, in two attempts, in bladder urine or, in one attempt, in day-old mice from an infected mother. Parallel observations made in the cotton rat, terminated at 269 days after infection, revealed a similar persistence of infectivity except in the brain (not infective at 269 days) and blood (infective at 102 days but not at 154 or 269 days.) Serum antibody was also demonstrated.

These observations suggest that of all the rickettsiae, with the possible exception of the immunologically similar Canadian vole agent, which was not sought in animals beyond 75 days after infection (13), R. orientalis is the most persistent in the tissues of rodent hosts. The equilibrium observed in the mouse most nearly parallels that observed in mouse carriers of lymphocytic choriomeningitis (2), with the interesting difference that the latter animals had little or no demonstrable serum antibody (of the neutralizing type), although they remained resistant to reinfection. Unpublished results of neutralization tests with sera from guinea pigs convalescent from infection with R. orientalis have revealed peculiar zonal effects (neutralization of large and of small but not of intermediate amounts of virus) which may help to explain the interesting simultaneous demonstration of infectivity and antibody in the same blood specimens. The significance of these observations to the problem of the rodent reservoir in Tsutsugamushi disease is obvious.
Characterization of the “Enzymic” Action of Influenza Viruses on Human Red Cells
Authors: Briody B. A.
Published: January 2023

Summary and Conclusions

Two capacities of the influenzal group of viruses (a) the agglutination of RBC, and (b) the elution or liberation of the viral particles from the RBC with concomitant receptor destruction, can be dissociated by appropriate treatment. Elutability can be destroyed by heating which is without action on the hemagglutinative titer; such heated virus can be liberated by RDF from RBC to which it is absorbed. The elutability of viruses is influenced in general by the same treatments and in the same direction as the activity of the soluble factor, RDF, derived from the cholera vibrio. The evidence presented is consistent with the hypothesis that a factor closely resembling RDF is an integral part of the surface of these viruses and that it plays an important role in the initial virus-cell interaction.
An Epidemic of Influenza a due to an Atypical Strain. The Relationship of This Strain to Other Influenza Viruses
Authors: Kalter Seymour S. , Chapman Orren D. , Feeley Doris A. , MacDowell Shirley L.
Published: January 2023

An epidemic due to atypical strains of influenza A appeared in the population regardless of prophylactic vaccination. High titers to the viruses in the vaccine were found in the acute phase sera indicating the potency of the vaccines. The relationship of these new strains to known viruses of influenza is discussed. Differences in strains occurring during the same epidemic have been found. No relationship between this epidemic and previously noted increases in antibodies to the porcine virus could be determined. The data suggest that the new strains were introduced into a highly susceptible population. Precautions against interference in the isolation of influenzal viruses must be taken.
The Incidence of Neutralizing Antibodies for Type A and Type B Influenza Virus in Normal Infants and Children
Authors: Lazarus Alfred S. , Westfall Robert E.
Published: January 2023

Sera were obtained from 212 normal infants and children during the winter and spring of 1947, and the neutralizing antibody titers for types A and B influenza viruses were obtained, using the Hirst agglutination-inhibition technic. Titers ranged from below 1–20 up to 1–1280, with the majority between 1–20 and 1–160. There was some indication of a higher average titer for type B than for type A. The data reported herein should supply basic information regarding the incidence of neutralizing antibodies in normal infants and children during a nonepidemic period.
Activity of Hexenolactone against Salmonella Enteritidis in Mice
Authors: Bartholomew James W. , Johnson Charles W.
Published: January 2023

The toxicity of hexenolactone as measured by the L.D.50 for 14 to 18 gram white mice on intraabdominal injection was 4.69 mg. Single injections of 1 mg of hexenolactone gave significant protection for 14 to 18 gram white mice against 100,000 cells of Salmonella enteritidis. Protection was demonstrated even after a 12 hour lapse between the injection of the organisms and the hexenolactone.
The Differentiation of Species of Trichomonads by Immunological Methods
Authors: MacDonald Etta Mae , Tatum A. L.
Published: January 2023

The study herein presented is concerned with the questions of identity of, or differences between, Trichomonas hominis and Trichomonas vaginalis, and for comparative purposes Trichomonas foetus is included. The two former named organisms have been generally assumed to be of different species, the T. hominis being a form whose habitat is the intestine, whereas T. vaginalis is found in the human vagina and only occasionally in the prostate gland of man. T. foetus is the common pathogenic form found in cattle. The approach employed in this work is that of serological technic.

Antigens derived from bacteria-free cultures of T. vaginalis and T. foetus have been studied particularly since these cultures have become available (1, 2). Byrne and Nelson of this laboratory (3) studied the nature of immunity to T. foetus infections in rabbits, but could not correlate resistance to infection with agglutinative titers in the blood of animals which were infected intravaginally or injected intravenously with living trichomonads.
Therapy of Experimental Brucella Infection in the Developing Chick Embryo
Authors: Shaffer James M. , Spink Wesley W.
Published: January 2023

Summary and Conclusions

A reliable and consistently reproducible method for testing the therapeutic activity of drugs against Br. abortus infection in the 7 day chick embryo is described. Using this method, streptomycin, sulfadiazine and combinations of the two drugs were tested. The results with a water soluble, chemical combination of streptomycin and sulfadiazine (Commercial Solvents S.D.-2) are reported. Combination therapy with streptomycin and sulfadiazine is superior to either drug used alone. The effectiveness of combined therapy against Br. abortus in the chick embryo is due to a streptomycin-sulfadiazine potentiation, rather than merely to an additive effect of the two drugs.
II. A Study of the Serological Relationships of Pneumococci from the Upper Respiratory Tract with Special Reference to Common Colds and Influenzal Conditions
Authors: Cooper Georgia M. , Mishulow Lucy , Blanc Ninette E.
Published: January 2023

This study forms a part of a general investigation by the Bureau of Laboratories and the Influenza Commission of the Metropolitan Life Insurance Company of the flora of the respiratory tract in normal and pathological conditions. The purpose of this section of the work was to determine whether any one variety of pneumococcus would be encountered more frequently in epidemic inflammatory conditions resembling influenza than in those of the nature of ordinary colds and in the normal controls. If, in a wave of common colds or influenzal-like inflammations, a dominant variety could be demonstrated in the majority of cases it would suggest strongly that the pneumococcus strain in question was the primary causative agent of the outbreak in which it was prevalent. The presence of a single type of a pathogenic variety in the individual case may indicate, however, that it is either the primary agent or one of the secondary invading bacteria; or that it may be only an accidental parasitic variety.
Polyvalent Antibody Response to Multiple Antigens
Authors: Huntoon F. M. , Craig S. H.
Published: January 2023

The simultaneous production in a single individual of antibodies against each of a number of strains of bacteria or bacterial antigens is not only of theoretical interest but of practical value as well.

The employment of prophylactic immunization against disease and the use of immune sera to combat specific infection would be greatly facilitated if an adequate antibody production combined with a wide polyvalency could be assured.

The possible objections to such immunizations are entirely based on the theory that the simultaneous treatment with a number of antigens does not produce as great an antibody response to each antigen as can be obtained with single strains or antigens.

It is undoubtedly true in many instances that attempts at multiple immunizations fail to produce adequate antibody response. But it is not true in all instances, and this leads us to examine the factors which limit such polyvalent antibody production.
Observations on the Agglutinative and Hemolytic Action of Calf Serum on Sheep Cells
Authors: Maltaner Frank , Johnston Elizabeth
Published: January 2023

The sera of four calves were found to agglutinate sheep cells. One of these sera produced strong hemolysis of sensitized sheep cells and partial hemolysis of unsensitized cells. The serum from one of the other calves produced slight hemolysis of both sensitized and unsensitized cells. The addition to the active calf serum of cytozyme in the forms of blood platelets caused the formation of a second clot. The serum from this second clot did not agglutinate or hemolyze sheep cells, either sensitized, unsensitized, or unsensitized in the presence of complement. The addition of anti-coagulants, sodium citrate or oxalate, to the mixtures of active calf serum and cells prevented the agglutination of the latter and completely inhibited their hemolysis except in one instance in which the citrate was mixed with active serum, unsensitized sheep cells and complement. Only partial inhibition was obtained with this mixture. Removal of the blood platelets from the sheep cell suspension reduced but did not remove the agglutinative action of the calf serum and did not affect the hemolysis.
Complementing Activity of the Blood Serum with Relation to Adrenal Deficiency
Authors: Ecker Enrique E. , Rogoff J. M.
Published: January 2023

The complementing power of the blood serum of rabbits is not modified by unilateral or bilateral adrenalectomy. The variations occurring are normal because the same variations are observed in the control animals.
The Action of Leucocytes and Brain Tissue on Diphtheria and Tetanus Toxins
Authors: Wadsworth Augustus B. , Vories R.
Published: January 2023

In any study of the action of the bacterial poisons on the leucocytes it is important to determine the chemical or physical reactions, if any, that take place between the leucocyte and the known bacterial toxins such as the diphtheria and tetanus toxins. Since the chemical or physical changes in these toxins are indicated and can only be measured by determining changes in the toxic effects they induce in susceptible animals, some experiments were done to detect any loss of toxicity in mixtures of diphtheria toxin and leucocytes such as Wassermann and Takaki (1) demonstrated with mixtures of tetanus toxin and brain tissue.

The results of these early studies, carried on in 1917, now have an additional significance since later experiments (2) have demonstrated the presence of substances in bacterial cultures which are adsorbed on the leucocyte and inhibit phagocytosis.
The Effect of Roentgen Irradiation on Antibody Formation in Rabbits
Authors: Craddock Charles G. , Lawrence John S.
Published: January 2023

Summary and Conclusions

A review and discussion of the literature concerning the effects of roentgen irradiation on antibody formation are presented. Also an analysis of current concepts of the relationship of lymphoid tissue and lymphocytes to antibody-production is given. Exposure of rabbits to 250 r whole-body roentgen irradiation results in a marked lymphopenia which lasts 30 to 40 days, and a mild depression of the polymorphonuclear leukocytes. Injections of antigen 8 hours after exposure to this amount of x-ray elicits an antibody response which is greatly depressed as measured by the titer of circulating antibody. This depressant action of x-ray on antibody formation is of a transient nature; the animals regained their ability to respond normally to antigen injection 40 days after exposure to x-ray. Whether this regained ability to produce antibody can be related to the return of the blood picture to normal cannot be stated. A non-specific “anamnestic response” of the antibody titer could not be elicited by exposure of the rabbits to either 20 r or 250 r whole-body irradiation. Exposure of rabbits to 250 r whole-body roentgen irradiation after the onset of antibody formation, but before a maximal titer is attained, in no way impairs the ability of the irradiated animal to produce circulating antibodies. In spite of marked depression of lymphoid tissue activity, as measured by the level of circulating lymphocytes, antibody-production proceeds at a normal rate, the titers reached being comparable to those of normal rabbits. A brief discussion of the experimental data is presented. It is concluded that the depressant effect of x-ray on antibody production cannot be related entirely to depression of lymphoid tissue. An adequate explanation for the remarkable difference in the effect of x-ray on antibody formation depending upon whether it is given before or after the onset of antibody production is not apparent. It is suggested that reserve sources of tissue must be capable of carrying out antibody formation once it has begun even though the major portion of lymphoid tissue has been damaged.
The Inhibition of the Anti-Trypanosomal Activity of Arsenoso Compounds and Acridines by Esters and Amides of Organic Acids
Authors: Schleyer W. L. , Schnitzer R. J.
Published: January 2023

Esters and amides of different isocyclic and heterocyclic acids were found to antagonize in vitro the immobilization of T. equiperdum by arsenoso compounds and acriflavine. The corresponding acids did not exert any inhibitory effect. For one member of this new group of inhibitors (methyl-p-hydroxybenzoate) the antagonism toward the trypanocidal effect of Mapharsen and Acriflavine was also demonstrated in vivo. Methyl-p-hydroxybenxoate also interfered with the inhibition of oxidases of E. coli by arsenoso compounds. These observations might lead to an explanation of the mechanism of the antagonism which cannot yet satisfactorily be interpreted on the basis of the present experimental evidence.
The Effect of Pyribenzamine in Beeswax on Experimental Meningoencephalomyelitis in the Guinea Pig in Beeswax on Experimental Meningoencephalomyelitis in the Guinea Pig
Authors: Alvord Ellsworth C. , Correll James W. , Ladd Anthony T. , Kellner Aaron
Published: January 2023

The repeated subcutaneous implantation of pellets of Pyribenzamine in beeswax into guinea pigs failed to influence the incidence or severity of the meningoencephalomyelitis induced by the subcutaneous injection of guinea pig brain and acid-fast bacilli in a water-in-oil emulsion.
The Relation of Antagonistic Coliform Organisms to Shigella Infections
Authors: Halbert Seymour P.
Published: January 2023

The antagonistic properties of the intestinal coliform flora of humans have been examined during the course of Shigella infections. Active organisms tend to appear and to increase soon after the onset of these infections, and to then decrease after several weeks. In some, but not all cases, antagonistic coliform strains were also active against Shigella strains with which the patient was infected. The composition of the coliform flora in several instances showed striking changes over periods as short as 2 to 5 days, as judged by examination of the antagonistic properties of sample strains from rectal swab cultures. Several subjects revealed shifts in the coliform flora, with appearance of antagonistic strains, in the absence of Shigella infections. The antagonistic properties of strains isolated from these Shigella infected patients have been shown to be due to the production of antibiotic substances. The ability of strains to produce antibiotic is a stable characteristic of the organisms. The observed shifts in the intestinal flora thus represent real changes in the bacterial populations, and not merely temporary non-hereditable alterations. In the present series of studies, 7,518 strains of fecal lactose fermenting bacteria have been examined for their antagonistic properties. Of them, a total of 1,351 (18%) have been active, 507 showing a high degree of inhibitory activity. The possible relation of such organisms to the recovery from and resistance to Shigella infections has been discussed.
Preparation of a Serological Antigen and a Vaccine for Experimental Tsutsugamushi Disease (Scrub Typhus)
Authors: Bailey Charles A. , Diercks Fred H. , Proffitt James E.
Published: January 2023

A method is described for the preparation of suspensions of Rickettsia tsutsugamushi. It was found that homogenized infected yolk sacs diluted with casein hydrolysate and differentially centrifuged yield relatively clean suspensions of the organisms. The suspension used as the antigen in complement-fixation tests reacts specifically with sera from animals convalescent from experimental tsutsugamushi disease. Mice inoculated intraäbdominally with the suspension show a substantial immunity when challenged with the homologous strain. The vaccine withstands lyophilization without apparent loss of potency. The heterogeneity of the serological pattern of various strains of R. tsutsugamushi was demonstrated by complement-fixation tests. Cross reactions with the various strains indicated the presence of common antigens in variable amounts depending upon the strain.
Infection of Guinea Pigs with Massive Doses of Rickettsiae of Epidemic and Murine Typhus
Authors: Gallardo F. Perez , Fox John P.
Published: January 2023

Discussion and Summary

A severe and often lethal disease, characterized by immediate onset and long duration of fever, significant weight loss, and frequently by the development of paraplegia, has been uniformly produced in guinea pigs inoculated with low dilutions of yolk-sac material infected with epidemic typhus rickettsiae. Bacteriologic cultures, passage experiments and immunologic evidence indicate that this disease was produced by the rickettsia and not by some other extraneous agent.

Evidence has been presented to show that the disease is more severe in large guinea pigs than in small ones, in intracardially inoculated pigs than in those infected by the intraäbdominal route, and possibly, in pigs inoculated during the cooler seasons than in those infected in warm weather. Although the brief incubation period suggests the possibility that the disease is a toxic manifestation similar to that produced in mice by inocula of the same kind, the long duration of illness and the pathologic changes observed suggest that a true infection has occurred. The greater susceptibility of larger guinea pigs, unexpected at first thought, is possibly analogous to the increasing mortality associated with age in human typhus.

Examples from the literature indicate that sources of abundant rickettsiae other than infected yolk sac, i.e., suspensions of lungs from intranasally inoculated animals (1) and of experimentally infected lice (3), may also produce severe disease in guinea pigs. To this list may be added suspensions of liver from intracardially infected cotton rats.

In our experience, both yolk-sac and cotton rat liver suspensions infected with strains of murine typhus rickettsia also produced more severe disease in guinea pigs than that ordinarily produced by more commonly employed inocula. However, lethal outcome was rare, and the onset of fever was usually delayed until the third day after infection. Not too surprising was the failure of intracardially inoculated animals to develop orchitis.

It seems possible that infection of guinea pigs with massive doses of rickettsiae may prove useful in future studies of the chemotherapy of typhus, or as the basis for the development of additional serum-neutralization technics. It has already served the purpose of helping to distinguish the avirulent Strain E of Rickettsia prowazeki from other strains of epidemic typhus rickettsiae (8), and it has proved to be a highly reliable challenge procedure, which lends itself to more certain interpretation than do the classical methods of challenge with less infective material of guinea pig origin.
The Experimental Production of Antibodies to Staphylocoagulase
Authors: Tager Morris , Hales Harriet B.
Published: January 2023

The antigenicity of staphylocoagulase for rabbits has been investigated by immunization with highly purified, though not homogeneous, material. Particularly with the aid of staphylococcal alpha hemolysin, enhanced neutralizing capacity against coagulase has been demonstrated in the blood, both by dilution of coagulase reacting against constant plasma, and by constant coagulase reacting with serial dilutions of serum.

Complement fixing antibodies appeared in the test animals, but not in controls, but precipitative tests remained inconclusive.

Positive collodion particle agglutination occurred, and its specificity was supported by the consistently negative findings in control animals and especially by the specific adsorbtion of neutralizing bodies from the serum by the coagulase-coated collodion particles of rabbits exhibiting positive agglutination, but not by negative test animals or controls.

The coagulase reacting factor was not significantly influenced by the immunization. Evidence is presented that besides specific antibodies, non-specific inhibitors may exist.
A Comparison of Antigenicity and Certain Biological Characteristics of 6 Substrains of Pasteur Fixed Rabies Virus
Authors: Wright John T. , Habel Karl
Published: January 2023

Substrains of Pasteur fixed rabies virus are not identical in their antigenicity, incubation period, duration of symptoms, pathology, or in their ability to overcome rabies immunity in immunized mice. Ability to overcome immunity would seem to be a sensitive characteristic capable of differentiating viruses of rabies of the same ancestry but of differing biological evolution and may be shown by methods of testing other than the intracerebral cross immunity test.
Further Studies on Oncolysis and Tumor Immunity in Rats
Authors: Lewis Margaret Reed , King Helen Dean , Aptekman Paul M. , Seibert Florence B.
Published: January 2023

Alcoholic extracts of rat sarcoma concentrated in vacuum to an alcohol content of 30 per cent resulted in a yellow fluid that had a hydrogen-ion concentration of 6.4 to 6.8. A precipitate occurred on addition of water, acid or sodium chloride but not on the addition of a phosphate buffer at pH 7.6 and μ = 0.1. The color reactions in nucleic acid diphenylamine, orcinol, carbazole, and tryptophane perchloric acid indicate a closer relationship to the ribose type than to the desoxyribose type nucleic acid. Chemical analyses showed presence of nitrogen and some phosphorus. More nitrogen was present than could be accounted for as nucleic acid. Some of it was probably protein nitrogen, as shown by the biuret test and also by the presence of extra selective absorption at a wave length of 2800 Å. Spectral absorption analyses of the rat sarcoma extracts exhibited a maximum absorption in the ultraviolet at a wave length of 2550 and 2600 Å, whereas similar extracts of human carcinoma showed one at 2500 Å. The former had a minimum absorption at wave length 2400 Å and the latter at 2300 Å. Intratumoral injection of rat sarcoma extract brought about oncolysis in 203 out of 210 rat tumors treated. Injection of human carcinoma extract into rat sarcoma showed some oncolytic action; tumors were destroyed in 15 of 25 treated rats. One hundred and forty nine of the 203 rats in which tumors had been destroyed by the injection of rat sarcoma extract were tested for resistance to tumor growth and proved to be resistant to further growth of rat sarcoma.
Purification, pH Stability and Culture of the Mumps Virus
Authors: Weil M. L. , Beard Dorothy , Sharp D. G. , Beard J. W.
Published: January 2023

Experiments on the multiplication of mumps virus in embryonated eggs showed that the greatest and most rapid increase of the agent in the chorio-allantoic fluid occurred in eggs inoculated after incubation for 7 days at 37.5 C. The highest levels of infectious capacity were reached on the 4th to 6th days after inoculation with seed virus and further incubation at 35 C. The increase in hemagglutinative capacity continued until the 8th post-inoculation day or the 15th day of total incubation. The discrepancy between the increases in the two properties of the virus was interpreted as due to inactivation of the infectious capacity of the virus in the chorio-allantoic sac without proportional destruction of the hemagglutinative property. The infectious titer of the chorio-allantoic fluid for embryos under optimum conditions was in the region of 109 50 per cent endpoint units per ml, and the average yield of chorio-allantoic fluid was from about 6 to 8 ml per egg, depending on the time of harvest. The pH of the chorio-allantoic fluid ranged from about 7.5 to 8.5 on the 4th and 5th days after inoculation, decreasing to a level of about pH 6.2 on the 7th or 8th day after inoculation. No differences could be seen in the virus yield resulting from the use of various dilutions, from 100 to 10−3, of previous passage chorio-allantoic fluid as seed virus. Penicillin and streptomycin or both together had no appreciable inactivating effect on the virus in 14 to 28 days and were useful in preventing bacterial growth in the titration in eggs of contaminated materials.

By means of ultracentrifugal and related procedures, the mumps virus has been concentrated and, judging from electron micrographs, obtained in preparations of considerable homogeneity with respect to particle kind. The particles vary greatly in size and shape, and in micrographs of untreated preparations, the average diameter of the images was 233 ± 35 mμ. In formolized preparations the average diameter was 171 ± 31.3 mμ. The particles were irregular in shape, some having an ameboid appearance. Many of the particles treated with formalin were flattened spheres in shadowed micrographs.

Sedimentation diagrams showed two boundaries broadly spreading, a principal one with a sedimentation constant of S = 1311 × 10−13 and a secondary peak of S = 1940 × 10−13.

The yield of nitrogen varied from 0.5 to 0.8 mg per 100 ml of chorio-allantoic fluid. The 50 per cent point infectious unit was about 10−13.5 gms of nitrogen, a value judged to be very high due to much virus inactivated during the purification procedure. The hemagglutinative unit was about 10−7.0 gms of nitrogen. The optimal range of pH stability was from 5.8 to 8.0 but about 99 per cent of the virus was inactivated in this range in 4 weeks.
The Significance of Antigen in Animal Tissues
Authors: Felton Lloyd D.
Published: January 2023

The subject matter of this address to the members and guests of the American Association of Immunologists is based on data accumulated over many years devoted to the study of pneumonia. With the advane of effective chemotherapy great strides have been made toward the cure of this disease. Yet there has been but little change in its incidence. Hence our efforts have been directed to studies which might prove helpful to a better understanding of this almost constant attack rate. Prevention may be possible at some future time. Indeed it will be but not until our alphabet of learning begins to spell words and make understandable sentences.

In the meantime several observations have been made that in our opinion may help to solve the equation of the incidence of pneumonia. The causes of any alteration in the symbiotic host-pneumococcus relationship are many and complex.
Studies on the Antigenicity of Toxic Extracts of Hemophilus Pertussis
Authors: Verwey W. F. , Thiele Elizabeth H.
Published: January 2023

Extracts of Phase I H. pertussis suspensions containing toxin and agglutinin-absorbing antigen (agglutinogen) were prepared by sonic disruption of the cells. These were found to immunize mice actively against intracerebral infection with virulent pertussis bacilli and to cause the formation of agglutinin and antitoxin when injected into rabbits. When the extracts were absorbed with pertussis immune serum containing no antitoxin, they lost their agglutinin-combining properties but toxicity and ability to combine with antitoxin were not diminished. However, in the absence of agglutinin-absorbing antigen, the toxin no longer was measurably antigenic in rabbits, and failed to protect mice from intracerebral infection with pertussis. These experiments indicate that the toxin in the sonic extracts probably exists as a molecule separate from the agglutinin-absorbing or major protective component and by itself has little antigenic ability. In the presence of agglutinogen it becomes antigenic but its contribution to prophylaxis against H. pertussis infection, if any, is very small.
Rh Hapten: Its Preparation, Assay and Nature
Authors: Carter Bettina B.
Published: January 2023

The current status of the Rh hapten has been described, first, as to preparation; second, as regards assay; third, in relation to its nature and properties and finally, a preliminary account of its clinical application has been presented. It is advocated that initial ventures with clinical use be interpreted with great caution.
An Evaluation of the Test for Antihemagglutinin in the Diagnosis of Infections by the Mumps Virus
Authors: Robbins Frederick C. , Kilham Lawrence , Levens Jeanette H. , Enders John F.
Published: January 2023

Introduction. In 1945, Levens and Enders (1) observed that the amniotic and allantoic fluids of chick embryos infected with mumps virus agglutinated the erythrocytes of the hen.1 This agglutination was specifically inhibited by high dilutions of serum of man and the rhesus monkey convalescent from mumps. Human sera taken early in the disease and normal monkey sera in most instances inhibited hemaggalutination only in low dilutions. But with certain specimens of normal or “acute” serum inhibition did occur with fairly high dilutions. Accordingly, at that time we did not recommend this test for antihemagglutinin in the routine diagnosis of infections by mumps virus, although obviously it is less complicated than the complement fixation test which had earlier been shown to be useful for this purpose (2).

Recent investigations have been undertaken directed toward overcoming the irregularities previously encountered in the test for antihemagglutinin.
The Relation of Shigella Type-Specificity and Susceptibility to Antibiotic-Producing Strains of Escherichia Coli
Authors: Halbert Seymour P. , Gravatt Margaret
Published: January 2023

The susceptibility of Shigellae to a small group of antibiotic-producing E. coli strains is related to type-specificity. Shigella sonnei strains proved the most susceptible, and Shigella paradysenteriae type VI the most resistant. With the eleven active E. coli strains tested, two patterns of such relationship were observed. The geographic sources of the Shigellae were not related to the above phenomena.
Studies on the Etiology and Pathogenesis of Experimental Meningoencephalomyelitis in the Guinea Pig
Authors: Alvord Ellsworth C.
Published: January 2023

The etiological factor responsible for the demyelinizing meningoencephalomyelitis which occurs in guinea pigs following a single subcutaneous injection of a water-in-oil emulsion containing killed tubercle bacilli and brain is apparently a heat-stable, phosphatide-like material present in the white matter of the adult central nervous system. The active material does not seem to resemble any of the five previously described brain-haptens, except possibly the alcohol-soluble one. The mechanism of its action is not yet known, nor is the relation between the experimental disease and the various demyelinating diseases of man known, except perhaps for its similarity to the paralytic accidents following rabies vaccination.
The Release of Histamine and Heparin by Antigen from the Isolated Perfused Liver of the Sensitized Dog
Authors: Scroggie A. Evelyn , Jaques L. B.
Published: January 2023

The response to antigen of the isolated livers of dogs sensitized to egg white and horse serum was studied by measuring the release of histamine and heparin. Significant amounts of histamine and heparin were released from the sensitized isolated liver perfused with Tyrode's solution on the addition of antigen (horse serum). In animals not so highly sensitized it was found that to obtain the release of histamine and heparin by antigen, blood was definitely superior to Tyrode's solution for the perfusing medium. The suggestion is made that blood owes this superiority to its ability to maintain the liver cells in good physiological condition for the reactions leading to the release of histamine and heparin after the union of antigen and antibody has occurred in these cells.
Therapy of Experimental Brucella Infection in the Developing Chick Embryo
Authors: Magoffin Robert , Anderson Dorothy , Spink Wesley W.
Published: January 2023

Previous reports have described a method for the evaluation of therapeutic agents against experimental Brucella infection, utilizing the developing chick embryo (1, 2, 3). Data comparing the relative effectiveness of sulfadiazine and streptomycin, individually and in combination, against infections in the chick embryo with each of the three species of Brucella have shown a definite synergism of these two agents when administered together.

The early reports of Pulaski and Amspacher (4, 5), Eisele and McCullough (6), and those from this Clinic (7, 8), have demonstrated the marked advantage of combined therapy with streptomycin and sulfadiazine in human brucellosis over previous methods of therapy. But this form of treatment possesses certain disadvantages. Because streptomycin must be injected intramuscularly, and because the antibiotic is potentially toxic, hospitalization of patients is essential. In addition to the expense of treatment and the threat of toxic reactions, relapses have occurred following the cessation of treatment.
Mechanism of Detergent Effect on Egg-White Inhibition of Hemagglutination by Formolized Swine Influenza Virus
Authors: Lanni Frank , Beard J. W.
Published: January 2023

The mechanism of the effect exerted by soaps and synthetic ionic detergents on the inhibition by egg-white (EW) of hemagglutination by purified formolized swine influenza virus (vaccine) has been investigated. It has been found that the effect is attributable to an interaction between detergent and the modified-virus particles of the vaccine such that the capacity of the vaccine particles to destroy the EW inhibitor is reduced; the capacity of the vaccine particles to combine with inhibitor or with red blood cells does not appear to be greatly affected by detergent under the conditions of the experiments. Under the same conditions, detergent has no effect, however, on the inhibition by EW of hemagglutination by unmodified swine influenza virus (SF) or by preparations of vaccine or SF which have been heated for 30 minutes at 53 C. Heating appears to have the same effect on vaccine as treatment with detergent; in each case the capacity of vaccine to destroy EW inhibitor is reduced, and the titer of EW inhibition against the modified vaccine is high. Some of the implications of the results have been discussed.
A Quantitative Study of Passive Anaphylaxis in the Guinea Pig. IV.
Authors: Kabat Elvin A. , Benacerraf Baruj
Published: January 2023

The non-precipitable or “univalent” antibody remaining after serial absorption of rabbit antiovalbumin sera has been found to be equally effective in inducing passive anaphylactic sensitization of guinea pigs as is an equal quantity of antibody from the original serum.
Quantitative Studies on Induction of Active Immunity to Smooth, V Form Salmonella Typhosa
Authors: Spitznagel John K. , Trainer Ranee Y.
Published: January 2023

Summary and Conclusions

The present study demonstrates that vaccines prepared from smooth V form S. typhosa killed with formalin, which has little effect on the Vi antigen, are more effective in the production of active immunity to experimental typhoid infection in mice than are organisms from the same culture killed with heat, which destroys the Vi antigen. The reduction in immunizing potency associated with heating was accompanied by a reduction in the agglutinability of the vaccine in specific Vi immune serum, and an increase in specific 0 agglutinability. The demonstration of differences in active immunizing potency was made possible by the use of techniques of assay similar to those used by Batson.

The demonstration of difference between the coefficients of regression for the two vaccines is presumptive evidence that the mechanisms of action of the two vaccines were qualitatively different. Qualitative differences could have arisen in the vaccines from antigenic differences produced by the methods of killing. However, the greater bacterial content of the E. D. 50 of the heat-killed vaccine could have been responsible for this effect. The factors could have acted alone or together to produce the effect, but we think that the possibility mentioned first is of greater importance.

It was found that mice immunized with heated or unheated vaccines were not sensitive to variations in challenge doses of the magnitudes involved in this experiment. The variations in challenge dose did not influence the reliability of the comparison of immunizing doses. This observation partially confirms similar observations made by Batson.
The Use of Adjuvants in the Production of Rh Antisera in Animals
Authors: Shatin Harriet Sommer , Boyd William C.
Published: January 2023

Human group O, type MN, Rh+ erythrocytes gave rise to adequate Rh agglutinins in six of 15 guinea pigs injected intraäbdominally with a plain cell suspension. Weak agglutinins were present in the nine remaining animals of this group. When Rh+ erythrocytes were incorporated into a water-in-oil emulsion with Falba, Bayol F and M. tuberculosis Jamaica #22, not only was there no enhancement of Rh antibody formation, but such agglutinin formation seemed inhibited. Thus the adjuvants used did not enhance anti-Rh production, but actually seemed to depress it. When stroma were prepared by Sharples centrifugation of the above erythrocytes, the material was poorly antigenic when tested by injection of the plain stroma. Stroma incorporated into the above emulsion also produced no Rh agglutinins when injected into guinea pigs. The peak of Rh agglutinin production was reached one to two weeks after weekly injections of the antigen were started. The peak of agglutinin production to the whole group O, type MN, Rh+ red cell and stroma was reached the fourth to sixth week after injection had been started. Despite continued injection of the antigens, guinea pigs producing Rh agglutinins no longer possessed these antibodies after two weeks. No Rh blocking antibodies were demonstrated. Guinea pigs do not seem generally to produce anti-Rh agglutinins comparable to those obtained from good human sera.
The Serologic Diagnosis of Mumps. A Comparative Study of Three Methods
Authors: Aikawa Jerry K. , Meiklejohn Gordon
Published: January 2023

As laboratory aids in the diagnosis of mumps parotitis and/or orchitis, the relative value of the complement-fixation test, the chicken cell agglutination-inhibition test, and the modified human-red-cell agglutination test was compared. The three methods demonstrated fold-increases in titer of approximately the same magnitude.

In the complement fixation test, infected allantoic fluid was found to be as satisfactory an antigen as the “viral” or the “soluble” antigens.

A rise in antibody titer was demonstrated early in the course of illness with all three tests. Modified-red-cell and agglutination-inhibiting antibody titers reached maximum values more rapidly than complement fixing antibody titers.

With the modified human-red-cell agglutination test, higher titers were obtained than with either of the other tests. Considerable difficulty was encountered in standardizing the test.
Studies on Diphtheria
Authors: Vahlquist Bo , Högstedt Curt
Published: January 2023

Schick tests and antitoxin titrations were performed on 143 subjects, divided into the following groups: Subjects with no demonstrable diphtheria antitoxin in their blood (<0.0005 A.U./ml serum; table 2); Subjects with diphtheria antitoxin in their blood due to active immunization (figure 2, table 3); Subjects with diphtheria antitoxin in their blood due to passive immunization with homologous antidiphtheric serum (figure 3, table 4). The results obtained permit the following conclusions as to the interpretation of the Schick test: The comparatively wide individual variations in the ratio between the size of the Schick reaction and the antitoxin titer of the blood are only partially explained by potential immunity. Non-specific individual differences of the skin play a role, which should not be neglected for the specific tissue factors. The possible implication of these findings for other skin tests is briefly discussed. On the basis of the results presented in this paper the following interpretation is given to Schick reactions of varying types.

A completely negative reaction is evidence of a previous antigenic influence and an antitoxin-titer usually above 0.002 A.U./ml.

A positive reaction, with a diameter of redness below 15 mm, is evidence of an antitoxin-titer always below 0.02 A.U./ml.

A strong positive reaction with a diameter of redness at or above 15 mm is evidence of an antitoxin-titer always below 0.005 A.U./ml.
Level of Serum Antibody Associated with Intracerebral Immunity in Monkeys Vaccinated with Lansing Poliomyelitis Virus
Authors: Morgan Isabel M.
Published: January 2023

Rhesus monkeys have been vaccinated intramuscularly with graded amounts of active Lansing poliomyelitis virus. The proportion of individuals immune to the subsequent intracerebral injection of 10,000 PD50 of active virus was found to rise with increasing dosage of vaccine.

In a total of 79 vaccinated monkeys, serum taken before intracerebral challenge was titrated by mouse neutralization test. As serum titer rose, a greater proportion of individuals proved to be immune. The minimal level of serum antibody associated with complete immunity of the group was found to be 3.0 (1/1000 dilution of serum).

These quantitative data give further information on the required level of serum antibody associated with immunity in an experimental animal, established by a severe test. They also provide us with an effective means of vaccination of monkeys which has served as a basis for type differentiation of strains of poliomyelitis virus.
A Delayed Chronic Inflammatory Reaction at an Antigen Depot in the Guinea Pig, Effected by Systemic Sensitization
Authors: Kopeloff Lenore M. , Kopeloff Nicholas
Published: January 2023

A delayed chronic local inflammatory reaction has been induced in the hind foot of the guinea pig by the simultaneous injection of an antigen-adjuvant emulsion with or without killed tubercle bacilli into the nuchal region, and of the same antigen without adjuvants into the hind foot. Normal rabbit serum, normal horse serum, rabbit anti-rat organ antiserums, therapeutic horse serum preparations, and crystalline chicken ovalbumin served as effective antigens. A chronic arthritic deformity of the foot followed the acute phase. The presence of killed tubercle bacilli in the antigen-adjuvant mixture enhanced the subsequent inflammatory response. It would appear that this phenomenon is an antigen-antibody reaction at a second depot of antigen, in which sensitivity of the tuberculin type may play a significant rôle. It is suggested that the mechanism responsible for the production of experimental allergic encephalomyelitis may be similar in nature to that involved in the local reaction described above.
Cold Hemagglutination Reactions with Influenza Virus
Authors: Overman John R. , Friedewald William F.
Published: January 2023

The following results were obtained in a study of hemagglutination reactions with influenza virus which occur only in the cold: Allantoic fluid suspensions of PR8 or Lee influenza viruses agglutinate sheep and rabbit red cells in high titer at 4 C but not at room temperature or 37 C.The cold hemagglutination is apparently due to the influenza virus particle, as indicated by specific inhibition of the reaction with antiserum and sedimentation of the hemagglutinin by centrifugation at 12,000 rpm for 30 minutes.Influenza virus heated to 56 C for 30 minutes agglutinates sheep cells at room temperature.The receptors of sheep cells can be removed by the action of influenza virus at 37 C, even though agglutination of the cells is not manifest at this temperature. Sodium periodate is also effective in removing the receptors.Human and chicken red cells, which have been treated with influenza virus so as partially to remove the receptors and the cells then stabilized with formalin, also show the cold hemagglutination reaction. Heated influenza virus, however, does not agglutinate the cells at room temperature.The receptors of human red cells involved in the hemagglutination reaction with isoagglutinins or bean extract, and the receptors of sheep cells which react with amboceptor or bean extract, are not affected by treatment of the cells with sodium periodate. Furthermore, Group A or B human red cells, which had been treated with influenza virus to remove the virus receptors, showed no alteration in their capacity to adsorb isoagglutinins.

The implications of these findings are considered in the discussion.
The Effect of Aureomycin Upon Infections with Bacterium Tularense in Experimental Animals
Authors: Larson Carl L.
Published: January 2023

Tularemia is an acute disease producing a mortality rate of about 5 per cent in human beings when not treated specifically. The prolonged convalescent period observed in untreated patients is most distressing. The use of streptomycin in the therapy of tularemia in man is based upon experimental results obtained from studies with mice by Heilman (1), and its efficacy has been adequately demonstrated (2). Recently a new antibiotic, aureomycin (duomycin), has been developed at the Lederle Laboratories (3), and its value as an agent in the therapy of various infectious diseases has been described (4, 5, 6). The results obtained in treatment with aureomycin of white mice, white rats and guinea pigs infected with Bacterium tularense will be presented in this paper. The data indicate that aureomycin is effective in the treatment of tularemia in these animals.

Materials and Methods.
The Solubility of Equine Tetanal Antitoxin in Methanol-Water Mixtures of Controlled pH, Ionic-Strength and Temperature
Authors: Wittler Ruth G. , Pillemer Louis
Published: January 2023

The solubility of equine tetanal antitoxin in methanol-water mixtures of controlled pH, ionic strength, and temperature has been determined.

On the basis of these determinations, three steps have been developed for the separation of tetanal antitoxin from other protein components of plasma. The relatively high ionic strength (0.2) at pH 5 and 10 per cent methanol which is employed in the second step contributes most to this separation.