bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of the Anaphylaxis Sensitizing and Adjuvant Properties of Hemophilus Pertussis Vaccine
Authors: Kind Leon S.
Published: January 2023

Pertussis vaccine administered along with chicken red blood cells (CRBC) in mice enhances the production of agglutinins to CRBC and also induces anaphylactic sensitivity to subsequent challenge doses of CRBC. However, the data presented indicate that serum agglutinins have little to do with mouse anaphylaxis. Pertussis vaccine stimulates the production of agglutinins to CRBC only if the CRBC are administered at the same time and via the same route as the pertussis vaccine. These conditions, however, are not necessary for the production of anaphylactic sensitivity.
Inactivation of Poliomyelitis Virus for the Preparation of Vaccines
Authors: Taylor A. R. , Kay W. W. , Timm E. A. , Hook A. E. , McLean I. W.
Published: January 2023

An extensive series of experiments designed to establish the practicality of combining formaldehyde inactivation with ultraviolet irradiation as a method for the inactivation of poliomyelitis virus for the production of vaccines has been reviewed. The actual use of the combination method is illustrated by safety, stability and potency test data obtained in a series of experimental vaccines. These vaccines were also subjected to trial in humans. The objective has been to introduce and illustrate the feasibility of producing virus vaccines according to standards (11), particularly poliomyelitis, by the use of a combination of chemical (formaldehyde) and physical (ultraviolet) methods of inactivation.
Relationship of Virulence for Mice to Patient Source of Type 2 Polioviruses
Authors: Habel Karl , Silverberg Rosalie J.
Published: January 2023

A total of 104 strains of Type 2 poliovirus, in first or second tissue culture passage, has been tested in mice. Eighty-eight produced paralysis by the intraspinal route; 15, with high titer intraspinally were positive by the intracerebral route. No correlation between tissue culture titer and mouse pathogenicity was apparent.

Comparison of clinical status of the patient source with tissue culture pathogenicity in monkey kidney epithelium showed an almost equal distribution of titers between patients with and without central nervous system (CNS) involvement. On the other hand, when the mouse intraspinal pathogenicity of the group of strains derived from patients without CNS involvement were examined in comparison to the results with the group from patients with CNS involvement there was a tendency for less virulence in the former group. This tendency for mouse CNS virulence to reflect virulence for human CNS was apparent only when the results for the entire 104 strains were considered since the whole spectrum of mouse virulence was represented by individual strains in both groups.

It is concluded that Type 2 poliovirus isolates obtained from human stools probably represent a mixture of mouse virulent and avirulent virus particles, both of which are pathogenic for monkey kidney epithelium in tissue culture and that the relative proportions of the two kinds of virus particles may be partially related to the type of clinical infection in the patient source.
Effects of Acute and Chronic Exposure to X-Radiation on Phagocytic Activity
Authors: Gyi Ko Ko , Marcus Stanley
Published: January 2023

Exposure of mice to total body x-radiation in doses of either 300, 400 or 500 r does not affect the phagocytosis by reticuloendothelial cells of spleen of intravenously injected ThO2 when determined 2 days following radiation. However, similar investigations carried out on the seventh postradiation day indicated that 1) x-radiation in a dose of 300 r did not affect the localization of ThO2 in spleens; 2) a 400 r dose of x-radiation causes a transient depression of localization of ThO2 at 2 hr but 6 and 24 hr splenic uptake values were not different from the controls; and 3) x-radiation in a dose of 500 r significantly depressed the uptake by the mouse spleen of ThO2 at 2, 6 and 25 hr after injection. Whole-body x-radiation in a dose of 550 r suppressed the phagocytosis by reticuloendothelial cells of LAf1 mice when tested on the seventh postradiation day.

Chronic exposures of mice to x-radiation in doses of 25 r three times per week until accumulated doses reach as high as 825 r did not affect the phagocytic function of the reticuloendothelial cells.
Study of Microbic-Tissue Affinity by Perfusion Methods
Authors: Manwaring W. H. , Fritschen William
Published: January 2023

The microbic-tissue affinity of an organ or group of tissues may be expressed as the average percentage of microörganisms deposited in these tissues per passage of a perfusion fluid. The microbic-tissue affinity varies with the organ or group of tissues tested. Thus, the central nervous system shows a microbic affinity of 0.5 per cent, the spleen a microbic affinity varying from 20 per cent to 60 per cent, and the liver a microbic affinity varying from 4 per cent to 80 per cent, depending upon the microörganisms tested. The remaining extra-hepatic tissues show affinities varying from 4 per cent to 6 per cent. The microbic-hepatic affinity is increased by immunization. The immune liver shows an affinity of at least 80 per cent for all microörganisms thus far tested. This increased hepatic affinity is due to the action of specific endothelial opsonins. The endothelial opsonins also increase the microbic-splenic affinity. So far as tested, however, they are inoperative with the other extra-hepatic tissues.
Hepatic Reactions in Anaphylaxis
Authors: Manwaring W. H. , Clark Wilfred S. , Chilcote Russell C.
Published: January 2023

Marked fall in arterial blood pressure is produced by intravenous injections of peptone into dehepatized dogs. Canine peptone shock and canine anaphylactic shock therefore cannot be regarded as physiologically identical reactions. Recovery from peptone shock does not take place in dehepatized dogs.
Some Relations between Hydrogen Ion Concentration and the Antigenic Properties of Proteins
Authors: Falk I. S. , Caulfield M. F.
Published: January 2023

Introduction. One of the outstanding contributions of recent years to the study of the chemistry and physics of the proteins is the demonstration that the reactions of these substances with electrolytes are capable of stoichiometrical analysis. The work of Jacques Loeb and his collaborators, in this country, and of Sorenson and many others has gone far in removing some of these reactions from the fields of more empirical colloid chemistry into the realms of classical chemistry. They have indicated certain important possibilities in the quantitation of the dynamics of systems containing proteins. It is not possible, nor is it desirable, to review this work here. It is perhaps sufficient to refer to the original papers by Loeb and others in the Journal of General Physiology (1918, to date) and to the concise summary in the recent monograph by Loeb (1922) and to the review by Bancroft (1922).
Studies in Endothelial Permeability. I
Authors: Petersen W. F. , Levinson S. A. , Hughes T. P.
Published: January 2023

In the following series of papers we describe experiments that deal primarily with observations on endothelial permeability as studied by means of lymph analysis. The number of theoretical as well as practical therapeutic problems that are related in an intimate way to alterations of endothelial permeability may justify a study such as this even though we already possess a great amount of information gathered in the laboratories of Ludwig, Heidenhain, Asher, Carlson, Starling and others. Much of the older work was carried out at a time when the knowledge concerning the physico-chemical factors that might modify the permeability of the endothelium had not been developed, while more gross forces, as osmosis, were perhaps over-emphasized. The more recent communications have been quite numerous and in them cognizance has been taken of the modern concepts concerning cellular structure.
Studies on Endothelial Permeability. VI
Authors: Petersen W. F. , Jaffé R. H. , Levinson S. A. , Hughes T. P.
Published: January 2023

During the many years that tuberculin has been used in the therapy of tuberculosis, years in which it has had as enthusiastic approval as it has had unqualified condemnation by clinicians the world over, the basis of its use has centered about the idea that in some way tuberculin had value in increasing the “antibody resistance” to the infection or in desensitizing specifically against the toxic products of the infection. Just how this was induced has never been satisfactorily explained. Yet we do know definitely that if it has value in some cases, that value cannot be due to the antibody mechanism. Increase in antibody concentration in the blood need bear no relation whatever to either clinical improvement or regression.

Granted that therapeutic results may at times be observed, how are they brought about?
Human Hypersensitiveness to Different Proteins of Horse Serum
Authors: Hooker Sanford B.
Published: January 2023

A triple reaction to horse serum has been shown to be due to specific hypersensitiveness, to serum albumin, euglobulin and pseudoglobulin. Thereby the evidence that these proteins are severally and specifically concerned with the manifestations of recurrent serum sickness is strengthened.
A Study of the Occurrence of the Blood Groups Among the American Indians
Authors: Coca Arthur F. , Deibert Olin
Published: January 2023

The inheritance of the Landsteiner isoagglutination elements of the human blood has been studied in two different respects.

Von Dungern and L. Hirschfeld (1) and, later, Ottenberg (2) and also Buchanan (3) have investigated the mode of transmission of the elements from generation to generation by the examination of the blood in parents and offspring.

L. Hirschfeld and H. Hirschfeld (4) on the other hand, have studied, in about 9000 individuals, the percentage distribution of the four blood groups in the different human races, and, in this way, these authors have obtained statistical data which seem to provide indirect evidence as to the manner of transmission of the blood elements, and which also offer a new means of studying racial relationships.

The evidence referred to lies in the Hirschfelds' observation that the percentages of “found” I and IV (Jansky) groups in the different races approximate the respective percentages which they calculated from those of groups II and III.
Factors Influencing Host-Virus Interactions
Authors: Walker Duard L. , Boring William D.
Published: January 2023

Exposure of adult mice to a cold environment (4°C) causes a loss of resistance to infection with the Conn.-5 strain of Coxsackie virus. In some respects this decrease in resistance appears similar to that brought about by treatment of mice with cortisone. Because this suggested that increased adrenocortical secretion stimulated by cold might be the mechanism by which cold exposure alters susceptibility to Coxsackie virus infection, experiments were designed to test this possibility. It was found that ACTH in doses sufficient to cause weight loss did not produce a detectable effect upon resistance to Coxsackie virus infection. A two-week period of adaptation of mice to cold prior to infection did not nullify the resistance reducing effect of the cold environment. When the effect of elevated environmental temperature (36°C) was compared with that of cold it was found that although the elevated temperature was a more adverse environment than the cold, as indicated by body weight gain, it had an opposite effect to cold and caused a marked inhibition of viral invasion and multiplication. It was further found that when exposure to a 36°C environment was applied as late as 36 hr after initiation of the infection at a time when viral multiplication was already well under way in the pancreas, viral multiplication was suppressed and the virus rapidly eliminated. These data were interpreted as strongly suggesting that the loss of resistance to Conn.-5 strain Coxsackie virus infection seen in adult mice at 4°C is not a consequence solely of adrenocortical hypersecretion.
A Passive Hemagglutination Reaction for Psittacosis
Authors: Benedict Albert A. , O'Brien Edith
Published: January 2023

Tannic-acid-treated sheep erythrocytes were sensitized with a soluble antigen sedimented at 100,000 × G for 80 min from meningopneumonitis infected allantoic fluids. Agglutination of sensitized cells was demonstrated with antisera from 22 (70%) of 31 humans who had experienced infections with psittacosis one to five years previous to tests. Four (13%) of 29 supposedly normal human sera manifested hemagglutinins. Substances responsible for nonspecific hemagglutination by normal human sera were adsorbed from the antigen preparation with untanned sheep erythrocytes. Evidence was presented that the hemagglutination and complement-fixation reactions measured different antibodies. Hemagglutinating antibodies were adsorbed from rabbit antipsittacosis sera with meningopneumonitis sensitized cells and complement-fixing antibodies were not removed by this treatment. The sensitizing antigen was not associated with either complement-fixation activity or with the murine hemagglutinin.
Studies on the Transfer of Lymph Node Cells
Authors: Harris T. N. , Harris Susanna , Ogburn Clifton A. , Farber Miriam B.
Published: January 2023

Filtrates of trypsin-treated suspensions of Shigella paradysenteriae (ST filtrates) were dialyzed in closed systems. The dialysates thus obtained were often found to have complement-fixing activity against anti-whole-Shigella serum. Evidence of antigenic material in such dialysates was also given by other serologic tests and by the appearance of agglutinins to Shigella in sera of rabbits injected with the dialysates. When lymph node cells of normal rabbits were incubated in vitro with such dialysates, washed and then transferred to fresh irradiated rabbits, agglutinins to Shigella appeared in the sera of the recipients. Within given ranges, higher agglutinin titers were found in sera of recipients of lymph node cells which had been incubated with dialysates of higher complement-fixation titers or with higher concentrations of given dialysates. Antigenic fractions of pyridine extracts of Shigella, prepared essentially according to Goebel et al. gave similar serologic reactions with anti-Shigella serum. Such extracts were also found to be effective for in vitro incubation with lymph node cells. Results of cross absorption tests among dialyzed ST, the ST dialysate described here and the pyridine-extracted antigen suggested that these were antigenically similar. On maintaining the pyridine-extracted acetone-precipitated antigen in solution, there was evidence of continued dissociation from it of dialyzable, antigenically active material. This dialyzable material was also found to be effective for in vitro incubation with lymph node cells in cell-transfer experiments.
Studies of the Inactivation of Phage by the Properdin System
Authors: Barlow James L. , Van Vunakis Helen , Levine Lawrence
Published: January 2023

Details are given of a method for measuring the neutralizing activity of human serum using bacteriophage as an indicator. The technique measures activity in terms of the 50% neutralizing unit and yields precise and reproducible results. Evidence is presented which suggests that the phage-neutralizing activity might be a reflection of properdin levels.
Quantitative Studies of the Properdin-Complement System
Authors: Leon Myron A. , Ransby Arnold
Published: January 2023

The formation of PZ proceeds optimally at a Mg++ concentration of 0.001 M-0.005 M. The PZ complex deteriorates at a rate proportional to the temperature. PZ inactivates C′3 in the absence of divalent cations. The inactivation is inhibited in undiluted RP, E.D.T.A. treated pig serum, or 1,3,4 fraction. The optimal range of pH for the reaction between PZ and C′3 is between 6.4 and 8.1.
Studies on the Immunotherapy of Bacterial Infections
Authors: Fisher Myron W. , Manning Mary C.
Published: January 2023

Pooled human γ-globulin exhibited therapeutic activity in mouse infections induced with a variety of bacteria, with this action being related to the dose of γ-globulin. In order of decreasing susceptibility were strains of Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Streptococcus salivarius, Streptococcus pyogenes and Diplococcus pneumoniae. Slight activity was noted against Salmonella typhimurium. The bacteria not affected by γ-globulin were Klebsiella pneumoniae, Pasteurella multocida and Streptococcus species, Group C. These findings appear to be consistent with the concept that normal antibodies are responsible for the described in vivo activity of γ-globulin.
An Immunochemical Study of the Relationship of Human Blood Group Isoantibodies to γ1- and γ2-Globulins
Authors: McDuffie Frederic C. , Kabat Elvin A. , Allen Peter Z. , Williams Curtis A.
Published: January 2023

Rabbit antisera were prepared to human γ2-globulin and to specific precipitates containing human isoanti-A and isoanti-B. The difference between the amount of antibody removed by A-anti-A and by dextranantidextran specific precipitate from anti-γ2-globulin sera was found to represent a small amount of additional antibody not detected by agar diffusion nor by the quantitative precipitin method. Antisera to A-anti-A and B-anti-B specific precipitates contain at least 3 antibodies, one of which is to γ1-globulin of S = 20 and another to γ2-globulin of S = 7. The capacity of these sera to give a Coombs test with anti-D and to enhance the saline agglutinating titer of anti-A and anti-B in the Coombs test depends on their content of anti-γ2-globulin.
The Reaction of Chicken Ovalbumin with Homologous Antibody in the Region of Antibody Excess
Authors: Nisonoff Alfred , Winkler Marvin H.
Published: January 2023

A pronounced decrease in the amount of precipitation in the region of antibody excess has been observed in the reaction of chicken ovalbumin with the concentrated globulin fraction of its homologous rabbit antiserum. A significant decrease was observed at a molar ratio of antibody to antigen of about 50:1, with almost complete inhibition at a ratio of 300:1. The results were confirmed with radioiodinated antigen; a much larger proportion of the antigen appeared in the supernatant in the prozone.

The amount of precipitate formed is dependent on the method used for mixing the two reactants. For maximum inhibition by excess antibody, it is necessary to add the antigen to antibody and to stir during the addition, so as to maintain constantly a high antibody to antigen ratio. A large effect of order of addition was observed; the inhibiting effect of excess antibody was greatly decreased when antibody was added slowly to antigen so that the proportions in the mixture passed through the equivalence zone.

Attempts to dissolve precipitates by extraction with excess antibody at 0° or 56°C have been unsuccessful. A high free energy of activation in the transformation of precipitate to soluble complexes is indicated.
The Roles of Time and Atabrine in Inducing Chronic Plasmodium Berghei Infections of White Mice
Authors: Cox Herbert W.
Published: January 2023

In an experiment to study time factors and quantity of Atabrine for inducing chronic Plasmodium berghei infections of mice, groups of mice inoculated with P. berghei were treated with a single injection of 0.5 mg of Atabrine, one group on each of the fourth, sixth, eighth, tenth, twelfth, fourteenth, sixteenth and eighteenth days after infection. In a second experiment, groups of similar mice were treated with 0.5 mg of Atabrine per mouse per day for 5 days, one group on each of the first, second, third, fourth, fifth, sixth, seventh, eighth and the ninth day after infection. In both experiments surviving mice were given a challenging inoculation of P. berghei to determine that they had been infected.

The results confirm previous observations that mice develop chronic P. berghei after treatment with Atabrine and are immune to super-infection. It was also shown that exposure to P. berghei infection for 6 days or more produced more chronic infections than did exposure for shorter periods. Further, it was shown that a longer period of treatment also enhanced the development of chronic infections.

It is suggested that the susceptibility of mice to P. berghei is attributable to the inability of this animal to withstand the burden of parasitism rather than the inability to develop acquired immunity to this parasite.
The Human Isohemolytic System: Complement Activity
Authors: Goodman Harold S.
Published: January 2023

Human serum as a source of C′ for the titration of human isohemolysins was found to have serious disadvantages. It is difficult to obtain such serum free of either hemolysin or dissolved blood group substance, either of which has a marked effect upon hemolysin titration values. It was found that guinea pig serum would serve as C′ equally well without the disadvantage of adding either interfering antigen or antibody. A possible reason for the necessity of using high concentrations of C′ in the human hemolytic system is discussed. Our findings with related hemolytic systems indicated that the requirement for high concentrations of C′ is a reflection of the specificity of human isohemolysins and the sparse distribution of the corresponding antigenic sites in the human red cell.
Studies on Antibacterial Factors in Mammalian Tissues and Fluids
Authors: Myrvik Quentin N. , Soto-Figueroa Eva , Naff George , Henelt Edward
Published: January 2023

The rabbit serum and human serum bactericidin systems for Bacillus subtilis were studied for participating cofactors. Both calcium ions and bicarbonate ions are required for activity of the human bactericidin, whereas only bicarbonate ions are required for the rabbit system. Bicarbonate ions must be present in the reaction mixture since cells grown on bicarbonate and then washed free of bicarbonate are not sensitive to the rabbit serum bactericidin. B. subtilis in the presence of sodium bicarbonate is not sensitive to egg white lysozyme which tends to rule out lysozyme as a major component of the serum systems. Antisera prepared against B. subtilis in rabbits neither influences the serum bactericidin levels nor alters the sensitivity of B. subtilis to the rabbit bactericidin.
Primary Antibody Response to a Distantly Related Heterologous Antigen During Maximum Depression Period After Varying Doses of X Radiation Antigen During Maximum Depression Period After Varying Doses of X Radiation
Authors: Makinodan Takashi , Gengozian Nazareth
Published: January 2023

Antigen administration by the intraperitoneal route stimulated greater antibody response than by the intravenous route in normal, adult mice. The 30-day LD50 dose for (C3H × 101)F1 mice was 756.3 r (95% confidence limits of 728.1 and 786.5 r). Antibody response for sheep red blood cells during the maximum depression period after varying doses of X radiation to the total body was measured in terms of a) inducation period, b) rate of antibody appearance in the circulation, c) mean peak titer and d) mean total titer. No quantitative relation between radiation dose and antibody response was apparent when mean peak titer was used as an index of antibody response. A curvilinear relation for the radiation dose and antibody response was obtained in terms of induction period, rate of antibody appearance, and mean total titer. The significance of these findings is discussed.
Studies on Toxoplasmosis
Authors: Cooney Marion K. , Kimball Anne C. , Bauer Henry
Published: January 2023

Comparison of complement fixation (C-F) analyses for Toxoplasma antibodies with peritoneal exudate (PE) and chorioallantoic membrane (CAM) antigens indicates that PE antigen prepared from whole peritoneal exudate has several advantages for use in diagnostic testing in spite of its being more anticomplementary and less reactive than CAM antigens.

The lower reactivity of PE antigen as compared to CAM antigen appears to be due to a later rise in titer and an earlier disappearance of reactivity to PE antigen. This has the practical advantage of permitting a rise in titer to be shown more frequently when PE antigen is used. In a limited number of serum specimens from symptomatic cases and possible active cases of toxoplasmosis, the PE and CAM antigens are equally reactive near the peak of the antibody response. With sera from normal persons, C-F tests with PE antigen are less frequently positive than with CAM antigen. The nonspecific reactions obtained with CAM antigens are a practical disadvantage. The study has shown no need to use a control antigen with PE antigen in routine diagnostic work.
Antigenic Variation in Relation to Classification of Shigella Flexneri
Authors: Okabe Kenzo
Published: January 2023

A technique to introduce phase variations of Shigella flexneri by means of antiserum was established studying various S. flexneri strains. The pathways of the antigenic degradation of S. flexneri were traced using this method, and the resulting variations were discussed in relation to classification of S. flexneri species.
Studies on Serum Bactericidal Activity
Authors: Donaldson David M. , Marcus Stanley
Published: January 2023

The intravenous administration of heparin into rabbits caused a temporary depression in the normal serum bactericidal activity. Serum and plasma exhibited less bactericidal activity than normal if either heparin or citrate was added to the blood in vitro immediately after withdrawal and prior to coagulation. In contrast, neither heparin nor citrate had a demonstrable effect on the serum bactericidal activity when added to the separated serum in vitro. The concentrations of citrate that inhibited bactericidal activity were anticomplementary when the complement titrations were carried out in saline. The heparin concentration used did not show a measurable anticomplementary effect with the test system employed.

The depression of bactericidal activity caused by the in vitro or in vivo addition of heparin to blood was partially reversed by the addition of protamine sulfate. The x-irradiation induced depression of bactericidal activity was not reversed by single or multiple injections of protamine sulfate.
The Specific Hapten of Group C (Group II α) Meningococcus
Authors: Watson R. Glenn , Marinetti Guido V. , Scherp Henry W.
Published: January 2023

The specific hapten of Group C (formerly Group II α) meningococcus appears to be predominantly a polymer of a sialic acid congener, as evidenced by its nearly complete conversion to humin-like material on aqueous acid hydrolysis, specific colorimetric analyses, infrared absorption spectrum, periodate oxidation, quantitative elementary and group analyses, correlation of sialic acid content with serologic activity, and conversion by hydrolysis in methanolic hydrochloric acid into products having characteristics of a sialic acid. Hexosamine determinations and nitrogen content indicate that this polymer contains hexosamine units as well as sialic acid units.
Immunochemical Analysis of Human Serum and Its Fractions
Authors: Oudin Jacques
Published: January 2023

The antigenic composition of the fraction of human serum soluble in ⅔ saturated ammonium sulfate and insoluble in saturated ammonium sulfate has been qualitatively and quantitatively studied. This fraction has been subfractionated in order to lower the competition of the main component toward the others in the immunization. Rabbits have been immunized against a number of fractions and subfractions. The immune sera have been allowed to react with fractions and subfractions, using precipitation in gels (simple diffusion in one dimension). The observed precipitation zones have been identified mainly by a method previously described. This method, based on the quantitative laws of penetration, requires no previous manipulation, e.g., preabsorption or reaction of several antigen solutions in the same medium. Eight distinct antigens have been demonstrated in the fraction studied. The concentration of six of them is larger in this fraction or in its subfractions than in any other fraction of human serum studied. These six antigens, considered to be the major components of the analyzed fraction, which corresponds to the fraction formerly called albumin, have been named A1, A2, A3, A4, A5 and A6. This order is probably not greatly different from the decreasing order of their concentrations in the serum. By suitable immunizations and absorptions, immune sera giving a single reaction could be prepared against seven of the eight listed antigens. The concentrations of five antigens in human serum and in the fractions have been quantitatively studied, using measurements of the penetration of the precipitation zones and the laws of penetration, previously described. Antigen A1 is the main component; it can be prepared in an almost pure state by techniques described long ago by other authors. Antigen A2 is very labile on aging even in the cold and on fractionation. It was not studied quantitatively. Antigens A3, A4, A5 and A6 have been quantitatively studied. Because of the lack of pure preparations of these antigens, their concentrations in the fractions have been expressed only in arbitrary units. Antigen A4 gives precipitation zones which vary somewhat from fraction to fraction. This can be explained by the heterogeneity of this antigen.
The Recall Phenomenon in the Antibody Response to Influenza Vaccines
Authors: Culver James O. , Lennette Edwin H. , Navarre George , Donahue Gwendolyn A.
Published: January 2023

Discussion and Summary

Orientation of the antibody response to influenza viruses by previous experience has been studied by several different approaches utilizing hemagglutination-inhibition tests (21–26). With this technique of antibody measurement, the data presented in this report afford primarily a confirmation of the earlier findings by an additional study design.

Orientation of antibody response in terms of the complement fixation reaction appears to be a new finding, even by the indirect method presented here. Indeed, in this study, the demonstration of strain specific reactivity of human sera seemed dependent upon the accentuating effect of prior antigenic experience. In addition, had not the distantly related PR-8 virus been used to measure the complement fixing antibody response to an A′ vaccine, the evidence for a “recall response” would have been rather unconvincing. In contrast, the effect of prior antigenic experience could be demonstrated with relative ease by hemagglutination inhibition tests with the much more closely related FM-1 and Cuppett strains; the highly strain specific reactivities of this technique presented difficulties in detecting a “recall phenomenon” with strains which are widely divergent antigenically, e.g., PR-8 and FM-1.

It has been previously noted (15–17) that allantoic fluids used as complement fixing antigens possess strain specific reactivities. Extensions of these studies, by Hoyle (18) and by Lief and Henle (19, 20), have further indicated that S antigens can be obtained in essentially pure form by means of simple differential centrifugation and adsorption techniques, and that these S antigens are type specific rather than strain specific. Even in the most purified preparations (19, 20), V antigens entirely free of S are not as yet available, and it appears that material with S reactivities forms an integral part of the influenza virus particle. In practice, V antigens actually represent a mixture of viral and soluble antigens. It seems reasonable to believe, therefore, that if a very highly purified viral antigen were utilized in contrast to the crude antigen employed in these studies, strain specific reactivity and the orientative effect of prior antigenic experience might be more readily demonstable.
Antigenic Analysis of Influenza Viruses by Complement Fixation
Authors: Fabiyi Akinyele , Lief Florence S. , Henle Werner
Published: January 2023

Methods are described for the production in guinea pigs of antibodies to the complement fixing V antigens of influenza viruses. The antisera were free of measurable antibodies to the type specific S antigen. Antisera were prepared against 34 variants of type A which were representative of isolates covering the years 1931 to the present, and to the Lee strain of type B. On cross-matching them with the corresponding V antigens they were seen to be highly strain-specific. The antigenic patterns so revealed were in general agreement with those obtained in other laboratories by hemagglutination inhibition. The results indicate that the complement fixation test can be employed for strain analysis, disclosing thereby major, minor and minimal components which comprise the mosaic of antigens of a given strain. The implications of applying the technique to other problems dealing with strain specificity are discussed.
Studies on the Complement Fixing Antigens of Poliomyelitis
Authors: Hummeler Klaus , Hamparian Vincent V.
Published: January 2023

The antibody responses of animals and man following infection and immunization with poliomyelitis viruses were investigated by absorption techniques.

Sera from animals, immunized with a single type of virus, contained two distinct complement fixing antibodies, both of which were found to be type specific. The presence of antigenic components common to two or all three types of virus was demonstrated by absorption of a chimpanzee and a human serum with heated antigen preparations. Absorption of a human serum with native type II antigen gave direct evidence that this type of virus in its native state contains antigenic components present in the two heterologous types of virus whereas types I and III absorbed only their homologous antibodies.
Concerning the Mechanism of Complement Action
Authors: Becker Elmer L.
Published: January 2023

C′1 and TAMe esterase activity can be eluted from sensitized sheep red cells containing C′1 activity by ethylenediaminetetraacetic acid. On dialyzing the supernatant from cells so treated against a low ionic strength buffer, both activities can be recovered. The C′1 activity eluted from red cells in this fashion can be detected with case by a two-step procedure of adding the “eluate” to sensitized cells, washing and then adding an R1. If an R1, sensitized cells and the “eluate” are added together little or no evidence for C′1 activity is obtained. The properties of the enzyme when removed from the cell are the same so far as studied as when the enzyme is attached to the cell. When sensitized cells are treated with the eluate not only does C′1 activity attach itself to the cells but esterase activity as well. Allowing the eluate to stand in the cold at pH 3.3, affects its TAMe esterase activity little of at all; however, the C′1 activity and the ability of the esterase to attach to sensitized cells is destroyed and, as kinetic studies showed, destroyed to the same extent. In explanation of these latter observations the hypothesis was evoked that the C′1 molecule contains two distinct sites, a binding site and an enzymatic site, and both are required in order for the molecule to manifest C′1 activity.
The Lack of Bactericidal Effect of Mouse Blood for Nonvirulent Group A Streptococci
Authors: Wiley Grove G.
Published: January 2023

Mouse blood in in vitro bactericidal tests is unable to sterilize even a small inoculum of certain group A streptococcal strains (327W and Type 1) which, on intraperitoneal injection into intact mice are shown to be of very low virulence. By contrast human blood is highly effective. The difference in growth-promoting properties of mouse and human blood appears to play no important role in this difference, nor does the relatively low neutrophil density of mouse blood.

Evidence is presented suggesting that the slowness of ingestion of streptococci by mouse neutrophils (allowing extracellular proliferation to proceed relatively unchecked) is an important factor contributing to the poor bactericidal power of mouse blood. However, the existence of a strain that is readily phagocytized, the growth of which is only moderately inhibited by mouse blood suggests that factors other than ingestion rate are concerned.
Depression on Normal Serum Bactericidal Activity by Nitrogen Mustard
Authors: Donaldson David M. , Miller Morgan L.
Published: January 2023

Single intravenous injections of 2.5, 3.0 or 3.5 mg of nitrogen mustard/kg caused a depression in the bactericidal activity of rabbit serum against Bacillus subtilis. The loss of serum bactericidal activity did not take place until about the third post-treatment day and returned to normal between the 14th and 20th days after nitrogen mustard administration. An intravenous injection of L-cysteine immediately prior to the administration of nitrogen mustard decreased the length of time that serum bactericidal activity was depressed following nitrogen mustard treatment. Nitrogen mustard treatment caused no statistically significant difference in either the natural agglutinins against Bacillus subtilis or circulating complement. Both circulating leukocytes and serum properdin were depressed by doses of nitrogen mustard that suppressed serum bactericidal activity. The serologic alterations, leukocytic changes, and the depression of serum bactericidal activity which follows near-lethal doses of nitrogen mustard were almost identical to those that follow exposure to near-lethal doses of total body x-irradiation.
Study on the Growth of Rickettsiae
Authors: Hopps Hope E. , Jackson Elizabeth B. , Danauskas Joseph X. , Smadel Joseph E.
Published: January 2023

The observed growth rate of Rickettsia tsutsugamushi (about 2- to 3-fold each 24 hr) in MB III and L929 cells maintained in an enriched medium suggests that slow multiplication is an inherent characteristic of the organism.

R. tsutsugamushi gradually died off in L929 cells maintained in simple nonprotein solutions which were incapable of supporting host cell proliferation. However, when infected cultures treated in this fashion were transferred to enriched medium, the remaining viable rickettsiae as well as the host cells began to multiply.

Rickettsial proliferation in L929 cells occurred at 25° C, 35° C and 40° C although at the lower and higher temperatures growth was somewhat delayed.

It is postulated here that the role of the adequately nourished host cell may be more than nutritional in supporting rickettsial survival in that it provides an environment which protects the rickettsiae from loss of their essential components by leaching.
Study on the Growth of Rickettsiae
Authors: Hopps Hope E. , Jackson Elizabeth B. , Danauskas Joseph X. , Smadel Joseph E.
Published: January 2023

Under certain conditions chloramphenicol can exert a rickettsicidal effect. L929 cell cultures heavily infected with Rickettsia tsutsugamushi were completely freed of their organisms after 3–4 weeks' treatment with 5 μg/ml of chloramphenicol; the rate of rickettsial inactivation by this concentration of antibiotic appears to be a function of temperature.

Sodium azide (1 × 10-4 M) exerted a more deleterious effect on intracellular rickettsial multiplication than either cyanide or dinitrophenol although all three substances had a similar inhibitory effect on the growth of L cells. Suppression of rickettsial growth by β-2-thienylalanine, ethionine and methionine sulfoxide occurred at concentrations which were not obviously toxic to the host cell.
Adaptation of the Antiglobulin Test for Use with Tannic Acid Treated Erythrocytes
Authors: Mathews Kenneth P.
Published: January 2023

Summary and Conclusions

A method of adapting the antiglobulin test for use with tannic acid treated erythrocytes is described. Prevention of nonspecific globulin adsorption from the antiserum by preliminary incubation of the sensitized, tanned cells with serum of another species is the essential feature of this procedure. The conditions required by the method are given in detail, and results are reported employing rabbit and human antisera. The method has proved sensitive and specific, and the results have been reproducible. However, the antisera titers have not been so high as those obtained with the direct tanned cell technique of Boyden when read by the pattern of cells sedimented in the bottom of tubes. The present method has usefulness in the study of antisera which ordinarily fail to give direct hemagglutination reactions with sensitized, tanned erythrocytes.
Studies on the Fate of Antigens in Vitro
Authors: Sorkin Ernst , Boyden Stephen V.
Published: January 2023

A method is described for studying the fate in vitro of I131-trace labeled human serum albumin in the presence of exudate cells from normal guinea pigs. When the cells were suspended in medium containing normal rabbit serum and normal guinea pig serum only slight breakdown of the albumin occurred. The addition of precipitating rabbit antihuman albumin serum to the system resulted in a greatly increased breakdown of the antigen. Although the amount of antigen precipitated by the antiserum was constant over the range of antiserum dilutions, 1:1 to 1:32, the amount of antigen broken down was greater in tubes to which the antiserum was added at 1:16 dilution than in higher concentrations of antiserum. In the dilutions 1:64 and higher there was a decrease both in the amount of antigen precipitated and in the amount broken down. The mechanism of this effect of antibody is discussed.

Evidence is presented that the antigen breakdown occurs intracellularly. Radiochromatographic analysis was carried out in order to identify the radioactive breakdown products, and the presence of a peptide was demonstrated.
Immunochemical Studies on Blood Groups
Authors: Allen Peter Z. , Kabat Elvin A.
Published: January 2023

The nondialyzable residue of mild acid treated blood group A or B substance (P1 fractions) can give rise in human beings to precipitins specific for the A P1 and B P1 fractions respectively. A P1 fractions differ from untreated A substance in that they are able to stimulate the formation of A P1 specific precipitins in group A as well as group O individuals. Similarly B P1 fractions differ from untreated B substance since they may give rise to B P1 specific precipitins in group AB as well as group O subjects.

Anti-B P1 precipitins are specific for groupings present in B substance which are exposed by mild acid hydrolysis since untreated B preparations show little or no reactivity with anti-B P1 sera but acquire this capacity following mild acid treatment. Hog A substances likewise show no capacity to remove anti-A P1 precipitins unless subjected to mild acid treatment. A single human A substance tested, however, was found to possess A P1 specificity prior to treatment.

Quantitative oligosaccharide inhibition studies indicate that B P1 specificity is partially determined by terminal nonreducing α-galactosyl residues. These α-galactosyl determinants of B P1 specificity appear to be involved in a linkage different from that of α-galactosyl determinants of blood group B specificity since melibiose which is very effective in inhibiting B-anti-B precipitation, is a poor inhibitor of B P1 anti-B P1, being even less effective in this system than galactose. Thus the galactosyl residues of B P1 determinant groupings are probably not in 1 → 6 linkage. Limited inhibition studies show anti-A P1 to differ in specificity from anti-A since N-acetyl-glucosamine is able to inhibit A P1-anti-A P1 precipitation but shows no inhibitory effect on A-anti-A precipitation.

The ability of B and B P1 fractions to precipitate anti-B is independent of the capacity of the same preparation to remove anti-B P1 precipitins. In agreement with inhibition studies this suggests that groupings determining B P1 specificity are distinct from those groupings conferring blood group B activity. In addition, time-hydrolysis studies of human B substance at pH 1.62, 1.32 and 1.10 show that reactivity with type XIV horse antipneumococcal sera as well as reactivity with human anti-B and anti-B P1 sera are affected in a different way for each specific antiserum further indicating distinct structural groupings to be associated with B, B P1 and type XIV cross reactivity.
Allergic Encephalomyelitis
Authors: Lipton Murray M. , Steigman Alex J.
Published: January 2023

By extraction of whole moist bovine spinal cord with petroleum ether, a fraction can be obtained which is highly encephalitogenic when combined with Freund adjuvants and injected intracutaneously into guinea pigs. Fractionation with acetone, chloroform and methanol yields a preparation which causes a high rate of allergic encephalomyelitis when injected in 5-γ amounts. This material contained 6.3% nitrogen. Further fractionation yields a fraction (almost completely protein) which is found to be highly encephalitogenic in 2-γ amounts.
The Antibody Response of Lymph Node Cells Transferred to Tolerant Recipients
Authors: Weigle William O. , Dixon Frank J.
Published: January 2023

Both a primary and secondary antibody response to BGG can be initiated by lymph node cells transferred to tolerant rabbits; whereas, only the secondary response to BGG can be initiated by similar cells transferred to x-radiated recipients. The relationship of these findings to the effect of x-radiation on antibody production was discussed.

It was postulated that the cells associated with recognition of antigens and/or production of antibody were the sites of unresponsiveness in rabbits tolerant to soluble protein antigens.
Studies on the Prevention of Mumps
Authors: Henle Werner , Crawford Mary N. , Henle Gertrude , Tabio Humberto Faz , Deinhardt Friedrich , Chabau Angel Guerra , Olshin Irving J.
Published: January 2023

Efforts were made to establish suitable dosage schedules for formalin-inactivated mumps virus vaccines. Susceptible children between one and eight years of age were selected on the basis of negative complement fixation (V antigen) and neutralization tests, as well as absence of “booster-type” responses following the first dose of vaccine. These were immunized by the subcutaneous route with 1-ml doses of vaccine at various time intervals. The results were evaluated in terms of anti-V and neutralizing antibody responses and, in one institution, by prevention of illness during an intercurrent outbreak of mumps.

A primary course of two doses, one to four weeks apart, following 6–12 months later by a booster dose, gave most satisfactory results. Many of the susceptible children formed some neutralizing antibodies within one to two weeks after the first dose, and nearly all after the second. A third injection at one- to four-week intervals was of little added value. Most of these children failed to reveal detectable antibodies three to six months after the initial dose. A primary course of two or more doses, nevertheless, protected five out of six children against disease during an outbreak of mumps three to eight months later. Subclinical infections were not prevented. The incidence of parotitis in children who had received only one dose corresponded to that in unvaccinated controls. Booster doses 6 or 12 months after the initial course rapidly recalled antibodies and to higher titers than those seen following primary vaccination. Neutralizing antibodies remained detectable in the sera of the majority of the children for 6–12 months thereafter. A second booster after a half year interval did not yield higher titers than elicited by the first. The booster responses in the vaccinated groups failed to match those observed in naturally immunized children following injection of vaccine.

The implications of these findings have been discussed.