bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Antigenicity of Tetanus Toxoids Prepared in the Presence and Absence of Veal Infusion
Authors: Stone Joseph L. , Berman Theodore
Published: January 2023

Tests were made to determine whether or not tetanus toxoid made with veal infusion or without veal infusion had equivalent or different antigenicity on an equal Lf basis. Fluid toxoids of each group were compared with each other. In addition comparisons were made between aluminum phosphate precipitated toxoids in combination with other antigens. No significant differences were obtained in the comparisons between toxoids prepared with veal infusion in the medium and those prepared in the absence of veal infusion insofar as antigenicity is concerned. A comparative antigenicity study for crude and purified fluid toxoids showed no significant differences in potency.
The Effect of the Order of Addition of Antigen and Antibody on the Precipitin Reaction
Authors: Neff Jane C. , Becker Elmer L.
Published: January 2023

Summary and Conclusions

The existence of the “order of addition effect”, that less precipitate is obtained when antiserum is added to antigen than when antigen is added to antibody, has been demonstrated for both rabbit and horse antisera. The fundamental identity of this finding to the Danysz phenomenon was pointed out. The explanation offered previously for the Danysz phenomenon, the disparity between the speed with which the initial reactions of antigen and antibody occur, and the slowness with which certain of the subsequent reactions take place, has been accepted for the “order of addition effect”. The presence of the order effect was used as a measure of the lack of equilibrium in the precipitin reaction.

With rabbit antisera it was revealed that under the usual conditions of incubation and refrigeration equilibrium was not attained in either antibody excess or antigen excess. With the horse antiserum studied, in confirmation of the work of Gitlin and Edelhoch, equilibrium was approached speedily in antigen excess, but much more slowly in antibody excess.

The removal of complement by treatment of the antiserum with versene or immune precipitate tended to diminish the order effect with some sera, but was without effect on others. In contradiction to the findings of Maurer and Weigle, versene tended to decrease the amount of precipitate formed with most rabbit antisera studied. The possible significance of these findings to the mechanism of versene action was briefly indicated. It was concluded that, as suggested by Kabat and Schorr, complement tends to decrease the velocity of certain of the antigen-antibody reactions.

With the horse antiserum studied versene was found to increase the amount of precipitate obtained in antibody excess, although a decrease was found in antigen excess and equivalence.
The Hemagglutinin of West Nile Virus: Recovery, Properties, and Antigenic Relationships
Authors: Chanock Robert M. , Sabin Albert B.
Published: January 2023

A specific hemagglutinin for chick erythrocytes was demonstrated in both unbuffered saline and pH 9 buffered saline extracts of the brain of 3 to 4 week old mice infected with the original (Uganda) strain of West Nile fever virus. In the unbuffered saline extracts (pH 7.1) much of the hemagglutinin was in large aggregates which sedimented at 13,000 rpm, while no such aggregates were present in the alkaline extracts (pH 8.1). Freshly prepared, 13,000 rpm supernates of the alkaline extracts produced hemagglutination between pH 6.7 and 7.5 or 8.0, but maximum titers (as high as 20,480) without zones of absent or poor agglutination in the lower dilutions were obtained at pH 7.1–7.3. After such preparations were stored at 4 C for 4 to 50 days the pH range shifted to the acid side with maximum titers at pH 6.7–6.9. The hemagglutinin in alkaline extracts was not destroyed by repeated freezing and thawing and could be maintained without loss of potency at -70 C.

To obtain the maximum titers it was necessary to mix the hemagglutinin with the red cells at 20 to 25 C and to permit sedimentation to occur at 4 C. With certain unbuffered saline extracts no reaction at all occurred when the reagents were at 4 C at the time of mixing, or if sedimentation occurred at 25 C. The reaction between the hemagglutinin and red cells is of the equilibrium type. Hemagglutination can be reversed by repeated resuspensions of the cells, because the uncombined hemagglutinin is unstable at the pH that is optimum for reaction. No receptor-destroying enzyme is involved because the addition of fresh hemagglutinin causes reagglutination of such cells.

When 3 other strains of West Nile virus (Egypt 19, 21, and 101) were tested no zone phenomena were encountered and fresh preparations yielded maximum titers at pH 6.7–6.9. Sedimentation at 4 C was needed to obtain maximum titers with strains 19 and 21 but not with 101. All 4 strains yielded identical hemagglutination-inhibition titers with specific antisera. The normal inhibitor present in human and animal sera was best eliminated by precipitating the specific antibody with acetone. Cancer patients experimentally infected with West Nile virus developed high titers of hemagglutination-inhibition antibody for the West Nile hemagglutinins and somewhat lower titers for the St. Louis and Japanese B virus hemagglutinins. Human beings naturally infected with the viruses of St. Louis or Japanese B encephalitis also developed hemagglutination-inhibition antibodies for all 3 viruses but the homologous titers were invariably higher. Hyperimmune rabbit sera for the 3 viruses showed much more extensive crossing by the hemagglutination-inhibition than by the neutralization tests. Hemagglutination-inhibition tests with West Nile, St. Louis and Japanese B hemagglutinins on “normal” Egyptian human sera gave positive results indicative of unrecognized infection only with West Nile virus.
The Incorporation of Radioactive Phosphorus into Influenza Virus
Authors: Liu Oscar C. , Blank Harvey , Spizizen John , Henle Werner
Published: January 2023

Studies have been presented on the labelling of influenza virus with P32 during propagation in the allantoic cavity of chick embryos. The labelled virus has been purified routinely by 2 cycles of adsorption onto and elution from chicken red cells with intermittent dialysis against large volumes of phosphate buffered saline solution.

The degree of radioactivity of the virus progeny could be improved by an increase in the dose of P32 used, by prolongation of the interval between injection of the isotope and infection, and by a reduction in the age of the embryos employed. The ratio between counts per minute and hemagglutinin units of the yields could be increased further by the use of deembryonated eggs instead of intact chick embryos.

It has not been possible to separate the radioactivity from the virus particles by various biological, physical and chemical means.

Chemical fractionation of labelled virus revealed most of the radioactivity in the lipid and nucleic acid fractions.
Studies on the Mechanism of the Immunological Paralysis Induced in Mice by Pneumococcal Polysaccharides
Authors: Felton Lloyd D. , Kauffmann Gladys , Prescott Benjamin , Ottinger Barbara , Kauffmann Gladys
Published: January 2023

Immunological paralysis has been defined as that condition produced in the host by an antigen given in such amount that a subsequent immunizing dose fails to stimulate active immunity. With the preparations of polysaccharide used in C3H mice the amounts included: For type I 500 μg or more, and for types II and III 50 μg or more. In white mice, one-tenth of these doses was sufficient to “paralyze” the defense. In both strains of mice, smaller amounts immunized the animal. The type-specific immunological paralysis persisted for at least 15 months following a single injection with type I or III polysaccharide and for 18 months with type II polysaccharide. For all three types studied, the reaction was essentially type-specific. Immunological paralysis was produced by 500 μg of type I polysaccharide by intraperitoneal, intravenous, or intradermal administration; but by the oral route the largest does given, 5.0 mg, immunized the mouse. For types II and III the 50 μg dose “paralyzed” the defense whether introduced intraperitoneally, intravenously, or intradermally; orally 5.0 mg immunized against type II, but not against type III infection. By subcutaneous route the “paralyzing” dose of 50 μg was the same for all three types. Repeated daily doses of smaller amounts “paralyzed” the defense when the total reached the above doses. With type I, this “paralysis” was not found in all mice; but with types II and III all mice so injected were unable to respond to a subsequent immunizing dose. Mice which had been previously immunized required four times as much antigenic polysaccharide to produce immunological paralysis as was required by normal mice. “Paralyzed” mice were found to be hypersusceptible to pneumococcus infection and required two to four times as much antibody to give passive protection as normal animals. The only successful means found for counteracting the “paralysis” in mice was the use of whole-cell vaccine, and this was applicable only to type I but not to types II and III.
A Study of Some Naturally Occurring Precipitins and Agglutinins of the Chicken: Reaction with Purified Blood Group Substances and Human Red Blood Cells
Authors: Baer Harold
Published: January 2023

It has been found that the sera of some chickens can precipitate with purified blood group substances of porcine and human origin, the ability to precipitate being independent of the blood group activity of the substances. All chickens thus far studied possess agglutinins for human red cells. The agglutinins were found to be different from the precipitins but both had properties that indicate them to be antibodies.
Tissue Tropism of a Strain of Influenza a Virus in Ferrets
Authors: Sugg John Y. , Nagaki Daizo
Published: January 2023

The study dealt with the occurrence of febrile reactions and with the multiplication of virus in different tissues of the respiratory tracts of ferrets following infection with the Cam strain of influenza A virus. All animals were infected by the intranasal route while under anesthesia. No evidence for multiplication of the virus in the lungs was obtained either during ten serial passages in ferret nasal mucosa, or during five passages in ferret lungs; the latter procedure was made possible by alternate passages in eggs. The results as a whole indicate that at least some strains of influenza A virus are non-pneumotropic agents in ferrets. The results also suggest that fever produced in ferrets by the intranasal inoculation of large amounts of influenza virus is related to the toxic properties of the virus particles rather than to processes involved in multiplication of the virus.
The Effect of Gamma Globulin on Subclinical Infection in Familial Associates of Poliomyelitis Cases
Authors: Brown Gordon C. , Rabson Alan S. , Schieble Jack H.
Published: January 2023

A previous publication (1) described quantitative serial fecal virus isolations from familial associates of reported cases of poliomyelitis and demonstrated that most subclinical infections present at the time of gamma globulin inoculation were not eliminated nor was the amount of fecal virus reduced. The serological data presented in this report show that active immunization by subclinical infection is not inhibited by the administration of gamma globulin.

Neutralization tests with paired sera from 15 of 23 individuals with subclinical infection demonstrated significant increases in antibody titer to the specific immunological type of virus with which they were infected. The remaining eight had high levels of specific neutralizing antibody in the first sera with no subsequent elevations in titers.

Twenty-seven of thirty-two familial associates who remained uninfected already had specific neutralizing antibodies to the type of virus isolated from their respective family groups. These findings are in accord with previous observations which suggested that virus is less likely to become established in persons in whom antibodies are present prior to exposure.

Uninfected volunteers were inoculated with gamma globulin of known potency, and low levels of antibody were detected after three days to one week and persisted for only two to three weeks. These results eliminate the possible role of residual passive antibody on the titers obtained with sera collected six to eight weeks after gamma globulin administration to familial associates of poliomyelitis cases.

Pharyngeal virus isolations were successful in 6 of 25 individuals who had demonstrable alimentary infection. In all cases, the immunological types of the viruses from stool and pharyngeal secretions were identical. No viruses were isolated from sera nor from stools six months after their intestinal infection.
Development of Immunity in Mice after Vaccination with Inactivated Poliomyelitis Virus
Authors: Krech Ulrich
Published: January 2023

The intraperitoneal inoculation of inactivated poliomyelitis virus type 2 into mice induces protection when given 3 days before intravenous infection.

The protection demonstrated is type specific, i.e., only the homologous antigen is effective.

A relationship between antigen concentration and proportion of survivors is demonstrated.
Pneumococcal Antigenic Polysaccharide Substances from Animal Tissues
Authors: Felton Lloyd D. , Prescott Benjamin , Kauffmann Gladys , Ottinger Barbara , Kauffmann Gladys
Published: January 2023

Polysaccharide-containing fractions have been prepared from 12 organs and tissues of mice 2 to 3 weeks after injection of 0.5 mg of specific pneumococcus polysaccharide type I, II, or III, an amount known to produce immunological paralysis. The materials stimulated a high degree of immunity in mice against the homologous pneumococcus infection. Similar fractions prepared from tissues of normal mice were devoid of immunizing ability. Those from most tissues of immunized mice (after a 0.002-mg dose of specific polysaccharide) were found to stimulate a low degree of immunity.

Tests of similar polysaccharide-containing fractions from tissues of albino and C3H mice 8 to 9 months after a “paralyzing” injection of specific polysaccharide showed that but little type I antigenicity remained, and no type III, but that high titer immunity against type II could still be induced by the homologous polysaccharides isolated from both albino and C3H strains of mice.

In one experiment similar fractions prepared from organs and tissues of guinea pigs and rabbits injected with pneumococcal polysaccharides, especially type II, stimulated some immunity in mice against homologous pneumococcus infection.
Antibody Production by Spleen In Vitro
Authors: Mountain Isabel Morgan
Published: January 2023

This study has provided new evidence that antibody can be formed in a culture of minced spleen from immunized rabbits. Rabbits were studied for H-agglutinin production after immunization with typhoid vaccine. Spleen removed four days after a single intravenous injection of vaccine served as the basis for the test system. Antibody production continued for as long as three days. The reproducibility of the test system was evaluated statistically in order to assay the effect of the addition of a variety of chemicals on antibody production.

Antibody formation in vitro required oxygen and was suppressed by sodium cyanide (10-2 through 10-4 M) and by salts of the heavy metals (at minimal concentrations indicated): manganous sulfate (10-3 M), ferric chloride (10-2 M), and cupric sulfate (10-4 M). Antibody formation in vitro was also suppressed in the presence of 100 mM sucrose and by the “essential” amino acids at 30 mM (combined total concentration) and by the reducing substances: reduced glutathione (15 mM), cysteine (15 mM or lower), and ascorbic acid (15 mM or lower) as well as by cortisone (32 mg %). With the exception of glutathione, and possibly sucrose, none of these substances (at concentrations which were found to be inhibiting) altered the antibody titer when incubated with immune serum. Thus, the various chemicals acted by inhibition of some phase of antibody formation by surviving cells in culture rather than by destruction of antibody once formed.
Effect of Oxytetracycline (Terramycin) on Agglutinin Titers in Guinea Pigs with Experimental Brucellosis
Authors: Carpenter Charles M. , Nelson Eric L. , Klein Sidney J. , Rawlings Bruce E. , Boak Ruth A. , Weimer Henry E.
Published: January 2023

A marked decline in agglutinin titers was observed in guinea pigs with experimental brucellosis treated with oxytetracycline.

The decline in titer did not result from the drug's interference with the host's mechanism to form antibodies.
The Preparation and Properties of Fractions of Pig Complement. II
Authors: Leon Myron A. , Plescia Otto J. , Heidelberger Michael
Published: January 2023

Two new fractions of complement have been isolated from pig serum containing C′1, C′3, and C′4, and C′1 and C′3, respectively. Probably because of their C′3 content, these fractions greatly enhance the lytic activity of gpC′. The maximal velocity of the reaction between EAC′1,4,2 (C′ cells) and the 1,3,4 fraction is directly proportional to the quantity of 1,3,4 added at constant EAC′1,4,2 concentration, and directly proportional to the EAC′1,4,2 concentration at constant 1,3,4 concentration. The concentration of C′3 was not appreciably diminished in the hemolytic reaction as carried out in these experiments.
Immunoelectrophoretic Studies on Serum Proteins
Authors: Williams Curtis A. , Grabar Pierre
Published: January 2023

Immunoelectrophoretic analysis by horse or rabbit antibodies of human γ-globulin suggests antigenic homogeneity, or at least a high degree of antigenic correspondence, over a broad range of electrophoretic mobilities.

Quantitative electrophoretic homogeneity and qualitative immunological purity are not necessarily of the same significance. A fraction such as γ2-W, which contains several non-γ impurities, may show a quantitative homogeneity of the same order as that of II-Sq, which is comprised uniquely of γ-globulin with asymmetric electrophoresis dispersion.

Subfractionation of a preparation of II-Sq into water soluble and water insoluble material at pH 7.2, and the separation of serum euglobulin from fresh serum gave evidence for the existence of complexes among human serum antigens, or for their formation by the fractionation procedures. The γ-globulins of different solubility appeared to have the same antigenic specificity.

The significance of serum complexes is discussed in relation to the nature and function of γ-globulin.
Influenza Virus Infection of Transplanted Tumors
Authors: Wagner Robert R.
Published: January 2023

Transplantation of Sarcoma 37, infected in vitro with neurotropic-WS influenza virus (NWS), to virus-immune mice resulted in rapid disappearance of infective virus from the grafts and unimpaired tumor growth. NWS virus, present as a “passenger” in attenuated sarcomas, was also rapidly neutralized after transplantation of the tumors to vaccinated animals. Neoplasms thus released from the tumor-suppressive action of the virus slowly recovered their normal growth potentials.

Administration of antiviral antibody, in the form of hyperimmune rabbit serum, to animals bearing infected Sarcoma 37 transplants completely neutralized the infectivity and tumor-inhibitory effect of NWS virus. The infectivity of the virus was not restored by retransplantation of these tumors to normal mice.

Passive immunization produced a somewhat slower decline in the infective titer of NWS virus in Brown-Pearce carcinoma transplants.

Infection of Sarcoma 37 grafts with the tumor-adapted FWS influenza virus also responded to treatment with homologous immune serum.

In contrast to neoplastic tissue, passive immunization did not alter significantly the course of NWS virus infection of adult mouse brain and lung or subcutaneous homografts of mouse fetal lung and kidney.

The results of these experiments will be discussed in conjunction with the studies on the Ehrlich ascites tumor presented in the following paper.
Incidence of Antibodies to Salmonellae among the Population of the Bronx, N. Y.
Authors: Weil A. J. , Saphra Ivan
Published: January 2023

Among the population of the Bronx, N. Y., a low incidence of agglutinating antibodies was found in tests including the following Salmonella antigens: groups B, C1, C2, and D, and flagellar b, d, i, and 1, 5.

The implications of these findings are discussed.
Mechanical Apparatus for Washing Tissue Cultures in Tubes
Authors: Hilleman M. R. , Taylor R. O.
Published: January 2023

A mechanical device for efficiently washing tissue cultures faster than by usual methods has been described.
Purification and Some Properties of Clostridium Welchii Type A Theta Toxin
Authors: Roth Florence B. , Pillemer Louis
Published: January 2023

Discussion and Summary

Theta toxin has been highly purified by fractionation of filtrates of Clostridium welchii type A in methanol-water mixtures under controlled conditions of pH, ionic strength, protein concentration, and temperature. By means of six fractionation steps, a product containing 2,450,000 theta hemolytic units per mg of protein nitrogen was obtained. This preparation was free of collagenase and hyaluronidase and contained less than 0.01% of the total amount of lecithinase activity of the parent filtrate. As judged from electrophoretic analysis, a value of 2,650,000 theta hemolytic units per mg of protein nitrogen was calculated for pure theta toxin.

The degree of purification depended upon the potency of the parent filtrate and upon the relative ratio of theta toxin hemolytic activity to lecithinase Lb activity which it contained.

Although no substrate other than the red blood cell has yet been found for theta toxin, certain of the properties of the purified hemolysin indicate that it might act enzymatically. The exceedingly small amount of activated hemolysin which produces lysis suggests its action is catalytic. About 2.5 × 10-6 mg of protein represents one hemolytic unit. This amount of hemolytically active protein lysed 6 ml of a 0.25% suspension of sheep red blood cells in 30 minutes at 37°C. It is improbable that such a small amount of protein could alter this concentration of red cells other than by catalytic action. The protein nature of theta hemolysin, its activation by —SH compounds, its pH and temperature dependence, also suggest that theta toxin is an enzyme. The manner in which activated theta toxin brings about hemolysis of red cells could be explained by the enzymatic attack of some constituent of the red cell membrane. However, the identity of this constituent is not known. Positive proof that theta toxin is an enzyme must await the identification of its specific substrate.
Murray Valley Encephalitis Virus: Its Serological Relationship to the Japanese-West Nile-St. Louis Encephalitis Group of Viruses
Authors: Pond William L. , Russ Sudie B. , Rogers Nancy G. , Smadel Joseph E.
Published: January 2023

An agent isolated by Australian workers in 1951 and designated as Murray Valley encephalitis virus has been characterized antigenically by the means of neutralization and complement-fixation tests and cross vaccination experiments. The MVE virus appears to be a new member of the JE-WN-SLE group of agents, more closely related antigenically to JE than to WN and SLE.

Results of neutralization tests on sera of Japanese Nationals suggest that MVE virus is absent from Japan, or that it infects fewer people than JE virus. Although half the sera tested contained MVE antibodies, these were invariably obtained from persons with large amounts of JE antibody and the MVE effect could probably be attributed to prior JE infection.

When 14 strains of supposed JE virus isolated in the Far East were re-examined in neutralization tests with JE and MVE immune rabbit sera of known specificity, all strains reacted as JE and none could be re-designated as MVE virus.
Studies on Organ Specificity
Authors: Rose Noel R. , Witebsky Ernest
Published: January 2023

Antisera produced in rabbits by injection of crude extracts of thyroid glands gave crossreactions with thyroid extracts of various species in an irregular and unpredictable manner, thus exhibiting a pattern similar to that observed by Hektoen, Fox, and Schulhof (1) with isolated thyroglobulins. Basically, identical results were obtained by complement-fixation and precipitation techniques. Antisera produced in dogs by the injection of the same crude thyroid extracts also contained thyroid-specific antibodies. Cross-reactions with thyroid extracts of other species were considerably less prominent than in the case of rabbit antisera. There is a considerable variation in the extent of cross-reaction, depending upon the individual animal used for immunization. This observation makes general statements about the degree of cross-reaction most difficult. Absorption with human serum of a human thyroid antiserum containing antibodies against human serum as well as thyroid extracts of different species resulted in the elimination of the species-specific antibody without influencing the thyroid-specific antibodies. Absorption of the same antiserum with human thyroid extract (the homologous antigen) resulted in removal of the entire antibody content of the serum. Absorption with hog thyroid extract eliminated the cross-reaction with both hog thyroid and beef thyroid extract but did not reduce the strong reaction with the homologous human thyroid extract. These findings were substantiated by both complement-fixation and precipitation tests. The extent of cross-reactions of thyroid antisera with thyroid extracts of different species was estimated by diluting in the same experiment both antigen and antiserum. Cross-reactions with the thyroid extracts of different species were considerably weaker than the reactions with homologous antigen. There is also an important time element in the evaluation of serological reactions of this type. In complement-fixation tests, cross-reactions obtained with the thyroid of heterologous species disappeared rapidly after further incubation at 37°C, whereas the reaction with the homologous antigen did not decrease significantly. In precipitation tests, the homologous reactions appeared first, while the crossreactions manifested themselves after further standing. The cross-reactions of thyroid antisera with thyroid extracts of other species are thyroid-specific. No reactions were detected with other organs of the heterologous species.
Studies on Organ Specificity
Authors: Shulman Sidney , Rose Noel R. , Witebsky Ernest
Published: January 2023

Crude extracts from hog thyroid glands show five sedimenting components. The extrapolated sedimentation constants (in Svedberg units) and the concentration dependencies (in terms of concentration, c, in grams per deciliter) are given in the following expressions: I, 29.5 – 2.69 c; II, 18.7 – 1.73 c; III, 11.3; IV, 6.5; and V, 4.2. The 18.7-component can be identified as the classical thyroglobulin; it comprises about 80% of the protein mixture. The nature of the other components is still unknown, but the thyroid origin of all of them seems to be established, primarily by means of perfusion studies. Electrophoretic examination by the filter-paper method reveals essentially one component. This has an approximate mobility in barbital buffer, pH 8.5, ionic strength 0.10, of 4.8 × 10-5 cm2 volt-1 sec-1, and is probably thyroglobulin.
Factors Affecting the Efficiency of the Aluminum Adjuvant in Diphtheria and Tetanus Toxoids
Authors: Levine Leo , Stone Joseph L. , Wyman Louise
Published: January 2023

The four most commonly used physicochemical states of the aluminum precipitate were compared in experimental animals as to efficiency as adjuvants for both diphtheria and tetanus toxoids, namely: AlPO4 preformed, and added to toxoid, and precipitated in the presence of the toxoid; and Al(OH)3 preformed, and added to toxoid, and precipitated in the presence of the toxoid.

Findings for the two toxoids were not the same. There were significant differences between the adjuvant states for tetanus toxoid, but not for diphtheria toxoid.

Tetanus toxoid adsorbed on a preformed precipitate was only about 60% as potent as when a nascent precipitate was formed in situ.

Similarly tested, AlPO4 as adjuvant for tetanus toxoid was only about 60% as potent as Al(OH)3.

The above findings with respect to tetanus toxoid were consistent in two experimental species, mice and guinea pigs.

In the case of both diphtheria and tetanus toxoids, the circulating serum antitoxin levels of immunized guinea pigs were highly correlated with their survival times after challenge with the corresponding toxin.
Virus Proliferation in the Mouse
Authors: Kalter Seymour S. , Berg Gerald , Prier James E. , Jochheim Kurt-Alphonse , McKenna John M.
Published: January 2023

Growth curves were constructed for the proliferation of influenza virus (mouse-adapted PR 8) in the mouse lung and mouse encephalomyelitis virus (Theiler's GD VII) in the mouse brain. The data obtained in these experiments indicate: 1) both viruses demonstrate cyclic development, 2) maximal infection occurs earlier with influenza virus than with TheileR′s GD VII, 3) the latent period, following inoculation for influenza virus, is approximately 1–3 hours, depending upon the size of inoculum. When very small inocula are employed, no virus may be detected during this latent period. An increase in amount of virus occurs and is followed by a leveling off of virus content for a period of approximately 6 hours. Again, there is another incremental period of about 3 hours and another plateau may be observed, which continues if maximal infection has occurred; 4) this pattern of proliferation is also observed with the GD VII virus except that the time intervals described for influenza virus are lengthened. Following the initial drop in titer after inoculation, there is a marked decrease in detectable virus followed by a latent period of approximately 3–6 hours. Cyclic periods of proliferation occur at approximately 6-hour intervals. From the above data and from reports on other viruses, it would appear that viruses, in general, proliferate within their host's tissues in a cyclic fashion.
The Metabolic Fate of Isotopically Labelled Proteins, Azoproteins and Azohaptens
Authors: Haurowitz Felix , Reller Herbert H. , Walter Harry
Published: January 2023

Sulfanilic acid as well as sulfanilazodyes, prepared by coupling diazotized S35-sulfanilic acid with tyrosine, histidine and phenol, were injected into rabbits. A small but significant amount of the injected activity was bound to the proteins of the blood and the tissues. The protein-bound radioactivity, 8–13 days after injection, was about 10 times lower than after the injection of equivalent amounts of sulfanilazoproteins. In the liver homogenate, most of the protein-bound azodye was present in the large cytoplasmic granules (mitochondrial fraction). When sulfanilazotyrosine was added in vitro to the liver homogenate, it was not bound to the proteins of the cytoplasmic granules. Rabbit serum γ-globulin (RGG), beef serum γ-globulin (BGG) and ovalbumin (OA) were coupled with traces or with large amounts of S35-sulfanilic acid. The heavily labelled sulfanilazoproteins were rapidly eliminated from the circulation and deposited in the organs in the same manner as heavily labelled iodoproteins. Trace-labelled OA behaved similarly, whereas trace-labelled RGG circulated in the blood for a long time without significant deposition in the organs. Trace-labelled BGG circulated in the blood over a period of four to seven days, after which time it was eliminated and deposited in the organs.
The Reactions Between Normal Human Red Cells and Antiglobulin (Coombs) Serum
Authors: Stratton F. , Jones Alan Richardson
Published: January 2023

It is demonstrated that normal red cells are capable of reacting with antiglobulin (Coombs) serum so as to reduce its power to agglutinate Rh sensitized cells.

The reaction is shown to be a specific combination between antiglobulin antibody and a globulin-like antigen on the normal cell surface.

This antigen may be modified by the action of trypsin in such a way as to render it non-reactive, but the reactivity of the cell may be restored by treatment with normal human serum.
Cellular Immunity of Monkeys versus Antibody Titers Following Oral Inoculation with Poliomyelitis Virus
Authors: Bachtold J. G. , Gebhardt L. P. , Wilcox W. C. , Bubel H. C.
Published: January 2023

A study was made concerning the relationship between humoral antibody titers and intracerebral resistance in monkeys infected orally with Type 1 poliomyelitis virus.

It was found that immunity to intracerebral challenge in those monkeys with little or no antibody was significantly higher than in comparable controls.

The possible significance of this observation is discussed and speculated upon.
Enhanced Production of Antibodies by Local Irradiation
Authors: Graham John B. , Leskowitz Sidney
Published: January 2023

Local irradiation with 1000 r of the site of injection of alum precipitated diphtheria toxoid results in an enhanced production of circulating antitoxin. There is an even larger increase apparent in the antitoxin content of the irradiated injected skin site.
Mechanism of the Teratogenic Action of Newcastle Disease Virus in the Chick Embryo
Authors: Williamson Alice Polk , Blattner Russell J. , Simonsen Lydia
Published: January 2023

Evidence has been presented indicating that defects in early chick embryos, after inoculation of allantoic fluid suspensions of Newcastle disease virus, resulted from the presence of the fully infective virus and probably were due to the proliferation of the virus since, in all circumstances observed, they were associated with this phenomena. Homologous immune globulin prevented the teratogenic action of the virus suspensions, and no teratogenic activity was found in suspensions from which the virus particles had been removed by ultracentrifugation. Virus inocula, inactivated by heat or ultraviolet irradiation, failed to produce defects. Inoculation of inactivated virus decreased somewhat the yield of abnormal embryos following subsequent inoculation of active virus.

There was no conclusive evidence that the rate of multiplication in organs, showing characteristic defects, was greater than that of tissues which appeared unaffected. It seemed clear, however, that virus proliferated in other tissues as well as those showing gross defects.

Microscopic studies showed that dilute virus inocula produced characteristic cell damage of a relatively mild type in comparison to the gross defects following concentrated virus inocula, but that the organ specificity was the same in either case.
Effect of Cortisone on Latent Syphilis in Rabbits and Mice
Authors: McLeod Charlotte P. , Magnuson Harold J.
Published: January 2023

Rabbits with latent syphilis, given large doses of cortisone, showed a decline in established levels of TPI and reagin antibody and an increased incidence of spirochetemia. An infectious relapse occurred in one rabbit. Cortisone had no effect on the development of TPI titers in syphilitic mice, but caused an increase in the infectivity of the tissues of mice which had received large infecting doses of organisms.
Studies of Enterobacterial Lipopolysaccharides
Authors: Neter E. , Westphal O. , Lüderitz O. , Gorzynski E. A. , Eichenberger E.
Published: January 2023

The effects of physical and chemical agents on the biological properties of purified enterobacterial lipopolysaccharides have been studied. The following observations have been made: The untreated lipopolysaccharides are markedly effective as antibody neutralizing antigens. They possess a high degree of toxicity and pyrogenicity, but they have only a limited erythrocyte-modifying capacity.Treatment of these lipopolysaccharides with heat or with sodium hydroxide for short periods of time results in an increase of their capacity to modify erythrocytes without alteration of their antigenicity (antibody-neutralizing potency) toxicity or pyrogenicity. Treatment with sodium hydroxide for longer intervals does not affect their antibody-neutralizing and erythrocyte-modifying capacity, but results in a marked loss of toxicity and pyrogenicity.Oxidation of the Escherichia coli lipopolysaccharide with periodate yields a compound of low toxicity and marked pyrogenicity. The capacity of this substance to neutralize antibody is almost completely abolished.A degraded, lipid-free polysaccharide component obtained from Salmonella abortus equi lipopolysaccharide exhibited reduced antibodycombining capacity when compared with the original product; treatment with heat and sodium hydroxide fails to produce any erythrocyte-modifying capacity.Red blood cells which have been modified with heated or sodium hydroxide treated lipopolysaccharides specifically absorb homologous bacterial antibodies. Erythrocytes which have been in contact with equivalent amounts of untreated antigens do not.The results of this study indicate that the various biological activities of bacterial lipopolysaccharides are affected differentially by different physical and chemical agents.The significance of the data has been discussed with particular reference to the relationship of chemical and physical-chemical characteristics of enterobacterial lipopolysaccharides and their components to the various biological activities of these compounds.
Kinetics of Human Complement
Authors: Leon Myron A.
Published: January 2023

The reaction between hu C′ and EA has been separated into two steps; (1) formation of EAhuC′A, and (2) reaction of this complex with C′3. Step 1 cannot proceed in the absence of Ca++, whereas Step 2 proceeds in the absence of any divalent cations bound by Na3E.D.T.A. Both the rate of formation and the rate of deterioration of EAhuC′A vary directly with temperature.
Serologic Relationship Among Meningococcal Strains in Norway
Authors: Jyssum Kaare
Published: January 2023

In direct bacterial agglutination experiments with 13 meningococcal strains isolated in Norway from 1952 to 1955, 3 distinct serologic types were observed. Two of the types corresponded to Group II and Group IIα, or Group B and Group C in the nomenclature proposed in 1950 by the Subcommittee of the Nomenclature Committee of the International Association of Microbiologists (1). The third type, that showed no agglutination in monovalent sera representative of Group I, Group II, and Group IIα, was provisionally named Type N.

Determination of the nitrogen quantities removed from homologous and heterologous antisera proved the presence of common antigenic substances in the 3 types. The distinct type difference was confirmed however. Strains from Type N appear to share some components with each of the other 2 types.

On cultivation of the microbes on immune serum agar plates, the specificity of a strain from Group IIα is associated with a “halo” phenomenon that is not observed in strains of the other 2 types.

An antigen sorption technique was used for the analysis. A method was established for extraction from meningococci substances that showed uniform and constant ability to render erythrocytes susceptible to the action of antibodies and complement. Common to the 3 meningococcal types was a serologically active nucleoprotein that was inactive in antigen sorption reaction.

The results from cross absorption with antigentreated erythrocytes were in agreement with the results of the quantitative agglutinin studies. The results have been summed up in a provisional theory of the relative antigenic constitution of the substances active in the antigen sorption reaction with meningococci.
Effects of Heat on the Sensitizing and Shocking Properties of Hemophilus Pertussis
Authors: Kind Leon S.
Published: January 2023

Heating at 80° for 30 min reduces the histamine-sensitizing property and destroys the anaphylactic and pertussis-sensitizing properties of Hemophilus pertussis. However, temperatures of 80° or 100°C fail to destroy the ability of pertussis vaccine to kill mice previously sensitized with unheated vaccine. It is suggested that the sensitivity of pertussis-inoculated mice to subsequent injections of pertussis may be an example of sensitivity to an endotoxin-like material rather than an example of an antigen-antibody reaction.
Immunization of Humans with A Chick Embryo Adapted Strain of Mef1 Poliomyelitis Virus
Authors: Roca-Garcia M. , Koprowski H. , Jervis G. A. , Norton T. W. , Nelson T. L. , Cox H. R.
Published: January 2023

Antibodies for Type 2 poliomyelitis virus developed in 5 of 6 human subjects fed a strain of chick embryo adapted virus alone, and in 9 of 12 individuals who were fed the same virus followed by the injection of immune serum globulin. Although the number of persons in this trial was not large, certain important results may be summarized: 1) No adverse clinical reactions occurred in any subject. 2) Viremia did not appear. 3) Specific antibodies were produced in 14 of 18 subjects. 4) Antibodies persisted for periods up to 8 months. 5) Only three of the 18 individuals excreted virus, after the 4th postfeeding day, and that was of low concentration. 6) The virus proved to be stable, since after human passage it was found to (a) retain its chick embryo adaptation characteristics, b) possess low cytopathogenic activity for monkey kidney cells in tissue culture, and c) to have low pathogenicity for monkeys inoculated intracerebrally.
A Misleading “Reaction of Identity” in Agar Diffusion Precipitin Studies of Tetanus Antitoxin
Authors: Jennings Robert K.
Published: January 2023

The displacement of zone growth by apparently nonspecific antibody—a phenomenon previously reported—is shown to be illusory. Comparable effects may be produced by specific antibody when used in sub-threshold concentrations. At the same time, evidence is offered to show that the presence of heterospecific antibody in a particular region of agar does not significantly change the path of zone growth through that region. The quantitative analysis of several antibodies in a polyvalent serum is therefore not complicated by possible additive concentration effects between physically similar molecules.

Internal evidence as to the relative antigen-antibody concentrations used in the present experiments suggests that the phenomenon was produced by qualitative, rather than quantitative relationships in this particular case. It is suggested that antibody formed in horses inoculated with toxoid for prophylactic purposes may have differed in specificity from antibody formed in horses used for tetanus antitoxin production. If so, the former was directed toward a portion of the toxin molecule which was altered or masked during the detoxification process, while the latter was specific for a determinant group which remained unchanged during the exposure of the antigen to formaldehyde.

Attention is called to the fact that, on logical grounds, the reaction of identity cannot be used in ascertaining the specificity of an unknown antibody unless it can be shown that antibodies from two different sources necessarily choose the same determinant group for their site of attachment to the antigen molecule. Since antibody from the scarlatinal antiserum is shown to compete with the antibody in tetanal antiserum for the same antigen, this principle may be said to have presumptive experimental support.
Behavior of the Rheumatoid Arthritis Agglutinating Factor with Immune Precipitates
Authors: Vaughan John H.
Published: January 2023

The ability of rabbit immune precipitates to bind the agglutinating activating factor in the serum of patients with rheumatoid arthritis has been described and the interaction of the factor with a component of normal Fraction II is indicated. The significance of these findings with respect to the sensitized sheep cell agglutination and inhibition are discussed.
A Comparative Study of Methods Used for Analysis of Specific Precipitates in Quantitative Immunochemistry
Authors: McDuffie F. C. , Kabat E. A.
Published: January 2023

A comparison of the sensitivity and precision of the biuret, ultraviolet absorption, Folin-Ciocalteu and ninhydrin methods for the analysis of specific precipitates has been made, and the uses and limitations of each have been discussed. The ultraviolet absorption of samples in 0.25 N acetic acid and the biuret methods were found to be simple and accurate, the limits of 2 S. D. being ±5 to 10%. The former may be used for samples containing as little as 5 μg nitrogen whereas the lower limit of the latter is about 20′ μg nitrogen. The Folin-Ciocalteu method may be used for samples as small as 5 μg nitrogen and 2 S.D. equals ±15%. The ninhydrin method has a sensitivity making it capable of determining as little as one microgram of protein nitrogen but for reproducible results should probably not be employed without the use of a standard.
Neutralizing Antibodies to Arthropod-Borne Viruses in Human Beings and Animals in the Union of South Africa
Authors: Kokernot R. H. , Smithburn K. C. , Weinbren M. P.
Published: January 2023

Sera collected from indigenous residents representing 51 localities in 44 zones of the Union of South Africa were tested for neutralizing antibodies against West Nile, Bwamba, Semliki, and Bunyamwera viruses. Similar tests with 5 other viruses were done with sera of residents representing selected localities. A total of 7,553 serum-virus tests were done, with a protective sera percentage of 2.6.

Highest incidence of sera protective against Sindbis and West Nile viruses was found in the elevated plateau region 3,000 ft or more above sea level. The converse was true of results with Bwamba and Bunyamwera viruses, in which case the highest incidence of positive sera was in donors residing in regions usually coastal at less than 500-ft elevation. A brief description is given of two localities, Luckhoff on the plateau structure and Simbu Pan on the coastal fringe, which illustrate geographic and climatic differences that may be correlated with immunologic results.

Sera from 9 of 63 donors from Durban were protective against type I (Hawaiian) dengue fever virus. Their age distribution is serologic evidence that the recorded outbreak of dengue fever in Durban in 1926–27 was due to that virus.

None of the sera tested against Ntaya and type II (New Guinea) dengue fever viruses was protective.

Sera from monkeys trapped in various localities in the Union were also tested. Of 413 sera tested, 78 had West Nile neutralizing antibodies. Negative results were obtained in 558 serum-virus tests with sera from a sample of the same monkeys against 5 other viruses.

Domestic animal sera collected on a farm near Johannesburg and specimens from immature birds collected on three lakes also near Johannesburg were found to have neutralizing antibodies against Sindbis and West Nile viruses. Indications were that the antibodies in the avian sera were of passive origin.
Vaccination against Smallpox
Authors: Jackson Elizabeth B. , Ley Anita C. , Binn Leonard N. , Smadel Joseph E.
Published: January 2023

Information is presented on the preparation of stable lyophilized vaccinia virus from chorioallantoic membranes of hens' eggs for use in immunization against smallpox.
Studies of Anti-Horse Crystalbumin Sera
Authors: Naylor G. R. E. , Adair M. E.
Published: January 2023

Evidence has been presented that the heterologous reactions with human and bovine serum albumin of anti-horse crystalbumin sera are due to their content of antibodies for horse crystalbumin and not to their content of an antibody for a protein present in only small amounts in the horse serum crystalbumin preparation. The range of antigen dilutions over which precipitation occurred was greater for heterologous reactions than for homologous reactions of approximately the same flocculation time.