bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal Immunity in Mouse Encephalomyelitis
Authors: Dean Donald J.
Published: January 2023

Passive immunity to mouse encephalomyelitis virus is transmitted from immune female mice to their offspring both prenatally by placental transmission and postnatally by the mother's milk. The motheR′s milk affords greater protection than placental transmission but resistance is greatest in baby mice acquiring immunity by both routes. The inhibiting agent in mouse milk is associated with the lactoglobulin fraction. The nature of the protective agent acquired by placental transmission is unknown.
Stimulating Effect of Tuberculin upon Production of Circulating Antibodies in Guinea Pigs Infected with Tubercle Bacilli
Authors: Boyden Stephen V. , Suter W. Emanuel
Published: January 2023

Guinea pigs infected with small amounts of tubercle bacilli and not subsequently skin tested did not produce, in detectable amount, antibodies which agglutinated sheep erythrocytes sensitized with old tuberculin.

When guinea pigs, previously infected with BCG, were injected with small amounts of old tuberculin, agglutinating antibodies appeared in the blood within 4 to 5 days.

Antibodies agglutinating erythrocytes sensitized with old tuberculin appeared also when BCG infected animals were injected with ovalbumin.

This stimulation by old tuberculin of the production of agglutinating antibodies did not seem to be correlated with the existing degree of skin hypersensitivity to tuberculin. However, the stimulating effect became apparent only after hypersensitivity was established.

The simultaneous injection of old tuberculin and ovalbumin into guinea pigs, either normal or infected with BCG, resulted in considerably higher titres of antibodies to ovalbumin than were produced by the injection of ovalbumin alone.

In order to avoid confusion of substances of bacterial origin which sensitise erythrocytes to agglutination by specific antibacterial serum with bacterial hemagglutinins, which themselves cause agglutination of erythrocytes, the term “bacterial hemosensitins” is proposed for the former.
Inoculation of Cynomolgus Monkeys with Coxsackie Virus Alone, Combined, or with Poliomyelitis Virus
Authors: Howitt Beatrice F. , Nichols Velma J.
Published: January 2023

Although three serologically distinct types of Coxsackie viruses of the A Group were not pathogenic for cynomolgus monkeys, these viruses could be recovered from sera, nasal washings, and feces after inoculations by the intracerebral, intracutaneous, intramuscular, intranasal, and intravenous routes. Viruses were isolated within 7 hours after inoculation and were demonstrable, in most instances, five to seven days later.

When intranasal instillations were made, neither the virus nor the neutralizing antibodies remained demonstrable for as long as when other routes of inoculation were employed.

Following simultaneous injection of two types of Coxsackie virus both could be demonstrated in certain animals; in others, only one.

Inoculation of mixtures of Coxsackie and poliomyelitis virus did not prevent infection with the latter agent. Both viruses were recovered from the nervous tissue of animals that succumbed to poliomyelitis after intracerebral or intranasal injection. Coxsackie virus, as well as poliomyelitis virus, was recovered after inoculation of the nervous tissue, but not the intestinal contents, of first passage animals to a second group of monkeys. Monkeys injected by various routes with Coxsackie viruses were not immune to a subsequent intracerebral inoculation of Brunhilde or Lansing poliomyelitis strains.

Antibodies neutralizing the Coxsackie strains usually appeared soon after the virus disappeared from the blood stream and persisted for at least one month, and in some cases up to 18 weeks, after the initial injection. When Coxsackie and poliomyelitis viruses were injected simultaneously, antibodies for both viruses appeared in the blood stream.
Studies on Immunization Against Plague
Authors: Silverman M. S. , Elberg S. S. , Meyer K. F. , Foster L.
Published: January 2023

A water soluble carbohydrate-protein immunizing antigen, Fraction IA isolated from Pasteurella pestis, was studied for its electrophoretic and serological homogeneity. Determination of the 50% immunizing dose of Fraction IA in mice showed that Fraction IA was a potent immunizing agent against infection with P. pestis. Twelve to 22 micrograms of the antigen were sufficient to protect 50% of the mice against 100 MLD of a highly virulent strain of the organism. The antigen preparations were electrophoretically inhomogeneous. Quantitative precipitin reactions showed that although the Fraction IA preparations were homogeneous on the basis of the analysis of the supernates, a serologically active minor component could be detected by absorption studies. However, the portion of the curves of the reaction for the zones of antibody excess and equivalence are believed to be the results essentially of the precipitation of Fraction IA and its antibody. The lack of complete inhibition of precipitation in the extreme antigen excess zone in the Fraction IA system was probably due, in part, to the serological activity of the minor component. However, removal of this component resulted in an increased but still incomplete inhibition of precipitation. This suggests that the carbohydrate moiety may be serologically active and may act in a manner similar to that of the pneumococcus polysaccharide. It is believed that the quantitative precipitin test, using a standard serum, can be used to assay preparations of P. pestis antigen by determining the amount of antigen required to bring the system to equivalence.
Evaluation of Serological Methods for Demonstrating Antibody Responses to Group A Coxsackie (Herpangina) Viruses
Authors: Beeman Edward A. , Huebner Robert J.
Published: January 2023

The virus neutralization and complement-fixation techniques were compared to evaluate their usefulness for demonstrating the serologic response of persons infected with some Group A Coxsackie viruses. Cases of herpangina and contacts harboring virus developed type specific neutralizing antibodies against the immunologic types responsible for the infections. The cases developed heterotypic complement-fixing antibody elevations against types not responsible for their infections. Similar elevations were not encountered in serums from other febrile illnesses. The presence of complement-fixing antibodies did not confer protection on several of the contacts in whose serums they occurred prior to infection. In paired serum specimens drawn at yearly intervals from control individuals there was little correlation between the presence of neutralizing and complement-fixing antibodies. The significance of these observations has been discussed.
Studies on Vi Antigen
Authors: Webster Marion E. , Landy Maurice , Freeman Monroe E.
Published: January 2023

A simple ethanol-salt fractionation procedure followed by acetic acid hydrolysis is described which yields a purified Vi antigen from saline extracts of acetone dried Escherichia coli, strain 5396/38. The various stages in the purification were accompanied by increased serological activity. The final product was the only fraction that was free from contamination with E. coli somatic antigen. This fraction showed a high degree of serological activity and specificity.

The residue left after extracting the bacterial cells with saline contained only 1% of the original activity as determined by mouse protective potency tests. On a dry weight basis, however, the saline extract was consistently less active than the intact bacteria. It is suggested that the presence of other antigens in the whole organisms may have influenced the response to the specific Vi antigen. Alternatively, the insoluble cellular components may have functioned as a depot substance which indirectly stimulated the production of Vi antibody.

The stages up to and including ethanol-salt concentration effected a 10-fold purification of the Vi antigen on a dry weight basis and a 25-fold purification on the basis of total nitrogen content. Chemical analysis at this stage revealed the presence of phosphorus, protein and carbohydrate. No differences were observed in the antibody response of rabbits to the various fractions up to this stage.

The next stage, shaking with chloroform-ethanol, removed only trace amounts of inactive material, yet the antigenicity of the product for rabbits was significantly reduced. No comparable reduction in antigenicity for mice was observed. Acetic acid hydrolysis liberated the Vi antigen from its complex without further impairing its antigenicity.

Chemical analysis of the purified Vi antigen showed that it is a fairly strong acid but that it does not contain uronic, sulphuric or phosphoric acid residues. Both nitrogen and acetyl groups are present, but apparently not in the usual form of N-acetylhexosamine.
Studies on Vi Antigen
Authors: Landy Maurice , Webster Marion E.
Published: January 2023

A study was made of the immunological properties of the Vi antigen obtained from Escherichia coli 5396/38 by a NaCl-ethanol fractionation procedure. The purified Vi antigen could be absorbed on collodion particles or on erythrocytes which then became specifically agglutinable by Vi antisera. It possessed excellent serological activity and specificity in these tests and also in the quantitative complement-fixation and quantitative precipitin tests. In the range of antibody excess the Vi antigen precipitated in a uniform manner the Vi antibody in coli, ballerup, typhoid and purified Vi-antisera. Supernatant fluid analysis in the quantitative precipitin test with E. coli antiserum indicated that the purified antigen approached but did not quite meet this criterion of immunological homogeneity.

The antigen was markedly effective in the protection of mice against challenge with virulent strains of Salmonella typhosa. It was antigenic for mice, rabbits and man, evoking the production of antibody reactive with both Vi antigen and with Vi strains of S. typhosa. The antibody produced in rabbits possessed mouse protective potency and in vitro activity essentially comparable to the Vi antibody obtained by immunization with Vi strains of S. typhosa, although certain differences in these activities were pointed out. The antigen was as effective as V form S. typhosa in the removal of mouse protective potency from various Vi antisera.
Quantitative Aspects of Influenza Virus Multiplication
Authors: de St. Groth S. Fazekas , Edney Margaret
Published: January 2023

Both live and inactivated influenza viruses when introduced into the allantoic cavity are distributed at random among the cells. The distribution is independent of the size of the inoculum. A single particle of inactive virus per cell completely prevents the multiplication in that cell of subsequently entering infective heterologous virus. A comprehensive theory is presented by which the regularities of heterologous interference can be predicted. Methods are described by which the number of available cells, the number of interfering particles, cycle time and the operative cyclic increment of virus can be measured.
Electron Microscopic Counting of Elementary Bodies of the Virus of Meningo-Pneumonitis
Authors: Crocker T. Timothy , Bennett Blair M.
Published: January 2023

Summary and Conclusions

The counting method of Backus and Williams is described as applied to enumeration of the elementary bodies of the agent of meningo-pneumonitis. The necessity of counting particles of biologic origin but of “indeterminate” nature, present in elementary body suspensions, is described. Homogeneity of the distribution of latex spheres, elementary bodies and other particles of biologic origin appears to be present in the results of this counting technic, at several concentrations of the elementary body suspensions. The estimates of concentration of biologic particles generally, or of elementary bodies alone, have a minimum standard deviation of about 3% resulting from instrumental limitations in determining diameter of latex spheres. Values for concentrations of elementary bodies, and of biologic particles generally, are reported, in which one standard deviation represents approximately 5% of the figure for concentration.
Influence of Preservatives, of Heat, and of Irradiation on Mouse Protective Activity and Detoxification of Pertussis Vaccine
Authors: Pittman Margaret
Published: January 2023

Portions of pertussis vaccines, prepared from cultures of one strain of Haemophilus pertussis grown on Bordet-Gengou medium for 48 hours were treated with 3 preservatives, heat at 34 and 56 C, and ultraviolet irradiation. After treatment all were held at 6 C. During the first year after preparation, frequent protective activity tests were made by the intracerebral method and again at the end of 3 years. Toxicity was determined at intervals, by intradermal reaction in rabbits and by death of or weight loss in mice, until each fraction was relatively atoxic. The best detoxification and stabilization of potency was obtained by heating the vaccine at 56 C for 30 min. or 1 day at 34 C and preserving it with merthiolate. Merthiolate alone had the least effect on both toxicity and potency. Phenol caused the most rapid loss in both properties. Formalin also reduced toxicity, caused some loss in potency and in addition clumping of the bacteria. Heating of the vaccines containing the 3 preservatives at 34 C for longer than 1 day and up to 7 days increased the rate of loss of potency, as the vaccines aged, in direct relation to the time of heat exposure. The amount of irradiation required to destroy toxicity markedly diminished the potency of the vaccine.
The Effect of Environmental Temperature on the Immune Response of Mice to Tetanus Toxoid
Authors: Ipsen Johannes
Published: January 2023

Mice were immunized with single doses of fluid tetanus toxoid, from 5 to 20 flocculation units, and divided in groups which were maintained for 14 days at respectively 6 C, 25 C and 35 C. Subsequently, the animals were all transferred to room temperature and challenged with 20 lethal doses of tetanus toxin. Highest immunity was shown in the mice submitted to the warmer atmospheres during immunization, the difference being most distinct with a low dose of toxoid. Variation in response to toxoid occurred among animals of different litters, and necessitated equal distribution of litter mates over the treatments.

The term immunizability is proposed to describe the inherent attributes of the host which determine the intensity of the immune response. Immunizability is distinct from factors of resistance which determine intensity of reaction to infection in non-immune animals.
Use of Antigen-Antibody Reactions in Agar to Follow the Progress of Fractionation of Antigenic Mixtures: Application to Purification of Staphylococcal Enterotoxin
Authors: Surgalla M. J. , Bergdoll M. S. , Dack G. M.
Published: January 2023

Antigen-antibody reactions in agar, modified from the technic of Oudin, have been used to determine the minimum number and to some extent relative concentrations of antigens in enterotoxic solutions at various stages of purification. A simple technic has been devised for direct identification of antigens responsible for bands appearing in different tubes. Resolution of superimposed bands has been accomplished by diluting the antigen mixture. An example of quantitative data which can be used to determine relative concentrations of antigens in fractions of a mixture is presented. Some aspects of practical application in the fractionation of mixtures of antigenic materials are discussed. Staphylococcal enterotoxin has not as yet been identified with a precipitating antigen demonstrable by these methods.
A Method for Removing Complement in Vivo and Its Rate of Return
Authors: Seltzer Gerard , Baron Samuel , Fusco Joseph
Published: January 2023

A method for virtually complete removal of complement from the blood stream in vivo has been described. A curve of reappearance of complement is presented and its significance discussed.
Identification of Coxsackie Viruses by Immunological Methods and Their Classification into 16 Antigenically Distinct Types
Authors: Contreras Guillermo , Barnett Vohammie H. , Melnick Joseph L.
Published: January 2023

232 strains of Coxsackie or C viruses isolated in widespread areas in this country and abroad, from patients, flies, and sewage, have been identified by the complement fixation and neutralization tests, and classified into 16 different immunological entities. The antigenic identification was done chiefly by using the unknown strains as complement fixing antigens. The results thus obtained were checked by neutralization tests. Seven immunological types were known at the beginning of the study, and nine additional ones have been recognized as a result of this work. Their classification was established by cross complement fixation and cross neutralization tests with all sixteen known C viruses. In 95 cases, the isolations had been made from individual patients, and in all, a strain crossing with a single type was recovered. In 5 instances in which the isolations had been made from pooled human stools, 3 crossed with more than one type. In 17 of 52 isolates recovered from flies, and in 8 of 80 from sewage, this multiplicity was also present. The separation of multiple strains into their individual components was accomplished in 10 cases. In the remaining 18, the results of the complement fixation and neutralization tests are indicative of multiplicity. The component viruses were identified, but separation of the strains was not attempted.
Precipitin Production in Chickens
Authors: Goodman Morris , Wolfe Harold R.
Published: January 2023

The similarity of pheasant and owl antibeef-albumin precipitins to chicken precipitins was demonstrated. At low salinity, about 1%, precipitation of these antibodies was very incomplete; on increasing the salinity the precipitation became more complete. The inhibition of precipitation in low salinity could readily be reversed by raising the sodium-chloride content of the reaction mixtures. Conversely, the maximal precipitates formed in high salinity, 8% to 12%, could be partially dissolved by resuspension in 1% saline. The precipitation patterns were interpreted primarily in terms of a decrease of the dissociability of the initially formed antigen-antibody compounds on increasing the salinity of the reaction mixtures.
The Role of Heat-Stable Antigen in Serological Identification of Proteolytic Clostridia
Authors: Mandia James W.
Published: January 2023

It is suggested that the somatic antigen of the proteolytic Clostridia be regarded as made up of a heat-stable and a heat-labile fraction. The heat-stable fraction of the 4 cultures studied was identical with that of group III organisms. The heat-labile fraction was identical with that of group II organisms. According to the reactions of the heat-stable fraction the organisms described were placed in group III; given the formula Prot. Cl. III: 5, 6 and identified as a new serotype of Clostridium parabotulinum.
Deposition of Small Doses of Injected Antigen in Rabbits
Authors: Crampton Charles F. , Haurowitz Felix
Published: January 2023

When rabbits are injected with very small amounts of I131-iodo-ovalbumin (0.01 to 0.05 mg per kg body weight), the highest concentration of the antigen is found in the proteins of the lung. The intracellular distribution in liver and spleen is the same as that when the dose is 1000 times higher, most of the antigen being deposited in the cytoplasmic granules.
California Encephalitis Virus, a Newly Described Agent
Authors: Reeves William C. , Hammon William McD.
Published: January 2023

Four species of mosquitoes, Aedes dorsalis, Aedes varipalpus, Culex tarsalis, and Culiseta inornata, remained infected with California encephalitis virus for at least 7 to 8 days after an infective meal.

In the laboratory Aedes dorsalis transmitted this virus to a rabbit on one occasion.
Stability of Sensitizing and “Blocking” Antibodies in Allergic Serum Following Ultraviolet Irradiation
Authors: Loveless Mary Hewitt
Published: January 2023

Summary and Discussion

The effect of ultraviolet rays on the potency of reagins has been judged by the results of serum-neutralization and of serum-dilution in normal human skin. Involved in the study were 6 samples of reagin-bearing serum donated by 3 adults who were allergic to one or more inhalant allergens (ragweed pollen, timothy grass pollen, horse epidermis, dog epidermis and cottonseed). The sera were examined over a long period, ranging from a few days to 2 years or more. Normal recipients of sensitizing mixtures or serum dilutions were restricted to 8 in number, so as to minimize the influence of the individual on the outcome. Thirty sets of experiments were done, each involving some 40 sensitizations.

Comparisons drawn between the light-treated and control portions of the same serum at the conclusion of each experiment revealed that no significant damage had been done by the rays in 17 instances whereas a slight reduction in sensitizing power may have resulted in 4, when the neutralization procedure was employed for the test. With the serum-dilution technic, no difference could be found between untreated and treated portions in 22 trials, a suggestion of lowered potency being noted in 2 experiments. The overall conclusion is that any adverse influence of ultraviolet light on sensitizing antibodies is so slight and infrequently encountered as to be of no practical significance.

In the case of the blocking, heat-stable antibody, limited observations on one timothy-immune serum indicated no loss of antigen-binding power during several experiments on 3 subjects.

The stability evidenced by the reagin, and presumably also the thermostable or blocking antibody, is consistent with the experience of numerous earlier investigators who showed that ultraviolet rays could be employed to inactivate bacteria and viruses (5–8) in the apparatus of either Oppenheimer-Levinson (2) or of Habel-Sockrider (9) without impairment of their immunizing qualities. Blanchard and associates (10) advocated irradiation as a means of protection against homologous serum hepatitis. The procedure has since been adopted by the National Institutes of Health (1) as a minimum requirement for pooled plasma which is destined for use in man. There are no reports in the literature on its application to sera which are to be appraised by tests of the Prausnitz-Küstner variety.
Purification Studies on Lansing Poliomyelitis Virus: pH Stability, CNS Extraction and Butanol Purification Experiments
Authors: Bachrach H. L. , Schwerdt C. E.
Published: January 2023

Lansing poliomyelitis virus in gently clarified homogenates is not measurably inactivated upon exposure to pH values 1.5 or 10.5 at 4 C for at least 24 hours. At pH values 3.6, 4.7, 7.1, and 8.4 this resistance is maintained over the entire 21-day period of observation.

A study of the extraction of the virus from crude homogenates revealed that partial liberation of the virus can be effected at pH 2.0, ionic strength 0.1, but not at ionic strength 1.0 or 5.0. At pH 7.0 the virus is readily extracted at ionic strength 1.0, but is not extracted at ionic strengths 0.01, 0.1, and 5.0. At pH 9.0 the virus is completely liberated at ionic strengths 0.1 and 1.0, but is insoluble at ionic strength 5.0. The degree of extraction effected was paralleled by a correspondingly high or low degree of virus purification. The highest relative infectivity of any of the fractions was 2.5.

The use of n-butanol under specified conditions of ionic strength and hydrogen ion concentration was effective in removing most of the lipid and non-virus protein from homogenates of Lansing-infected cotton rat CNS tissue. Relative infectivities up to forty were obtained without loss of virus.
A Procedure Which Eliminates Nonspecific Inhibitor from Human Serum But does not Affect Specific Antibodies Against Influenza Viruses
Authors: Tyrrell David A. J. , Horsfall Frank L.
Published: January 2023

All influenza virus preparations and red blood cells which were examined in hemagglutination-inhibition tests with normal serum were affected by nonspecific inhibitor. Experiments with human sera, from which influenza virus antibodies had been absorbed, showed that incubation with an equal volume of V. cholerae filtrate at 37 C for 18 hours completely inactivates nonspecific inhibitor. There was no detectable reduction in the titer of hemagglutination-inhibiting or neutralizing antibodies against influenza viruses in human serum treated with V. cholerae filtrate. After elimination of nonspecific inhibitor with V. cholerae filtrate, specific antibody responses against influenza or mumps virus were demonstrable with paired sera which yielded negative results when tested in the usual manner.
A Study of the Precipitin and Complement Fixation Reactions with Tuberculous Exudates with Special Reference to Tuberculous Pleuritis
Authors: Ogawa Isamu
Published: January 2023

This investigation was undertaken for the purpose of determining whether the immunological reactions of precipitation and complement fixation occur with pleural exudates of tuberculous origin, as additional means and aids for the differential diagnosis of pleural effusions. The necessity for diagnostic aids of this character has been impressed upon the writer since 1913, when he found large numbers of Japanese soldiers and many civilians in Mukden, South Manchuria, with mild pleuritis and exudates of unknown origin. At least 52 per cent of a group of forty-two of these individuals yielded negative v. Pirquet tubeculin skin reactions; cultures of the fluids from twenty-one were negative and tubercle bacilli were not found by smear methods. It is commonly believed that these “light pleurisies” (1) are of tuberculous origin but this has not been proven and the exact etiology is unknown.
The Production of Antibody by Patients with Acute Viral Hepatitis
Authors: Eichman Peter L. , Miller Ruth W. , Havens W. Paul
Published: January 2023

The amounts of antitoxin produced by 34 Schick-negative patients with acute viral hepatitis and 31 Schick-negative, essentially normal controls following the intramuscular injection of 50 Lf purified diphtheria toxoid were measured by titration in the skin of rabbits. The pre-Schick levels of circulating antitoxin were, on the average, significantly greater in the patients with acute hepatitis, but there was no significant difference between the subsequent qualitative pattern of production of antibody or the intensity of immunologic response of the two groups. There was no apparent relationship between the amounts of antitoxin produced and the age, severity of disease, or stage of disease in which toxoid was injected.
Evaluation of Prolonged Antibiotic Therapy in Mice with Chronic Brucella Infection Due to Brucella Melitensis
Authors: Shaffer James M. , Kucera Carrell J. , Spink Wesley W.
Published: January 2023

Summary and Conclusions

A chronic, sublethal Brucella melitensis infection was established in mice. Therapy with aureomycin, terramycin, sulfadiazine, or streptomycin, alone and in combinations, was started 4 weeks after establishment of the infection, and continued for 3 or 6 weeks. The results of therapy were evaluated by spleen cultures for brucella at the completion of treatment and 4 weeks after stopping therapy. The experimental results showed that any of the combined types of therapy with streptomycin plus aureomycin, terramycin, or sulfadiazine were definitely superior to any one of the drugs when used alone. Such combined therapy completely eradicated brucella from the spleens of all but 1 of 100 mice treated with any of these combinations. Therapy with aureomycin or terramycin alone in doses of 60 mg per kg per day for 3 weeks resulted in the eradication of brucella from the spleens in only 20 to 30% of the animals, as determined by spleen cultures at the completion of treatment. However, the final result of this therapy, determined by spleen cultures 4 weeks after stopping treatment, was eradication of the organisms in 70 to 80% of the animals. This observation emphasized the significant role of the host's immune mechanisms in the final eradication of brucella infections. Therapy with aureomycin alone in doses of 30 to 60 mg per kg per day for 6 weeks produced, as an immediate result, eradication of brucella from the spleens in 75 to 100% of the animals. However, the final results of this prolonged therapy, as determined 4 weeks after stopping treatment, were no better than the final results with only 3 weeks of treatment.
Studies on the Bactericidal Reaction
Authors: Adler Frank L.
Published: January 2023

Summary and Conclusions

Data have been presented which support the view that specific bactericidal sensitization of Salmonella typhosa O 901 cells is impeded by the action of a second antibody directed against a widely distributed antigen (R-antigen). This inhibiting antibody has been shown to mediate the bactericidal sensitization of S. typhosa O 901 cells which had been coated with an antigenic extract obtained from R-state cells. The presence of some R-receptors on the surface of unmodified S. typhosa O 901 cells has been demonstrated, and it has been suggested that other apparently S-state Salmonella strains also possess on their cell surface a small number of exposed R-receptors. The possibly intimate spatial association of R-receptors with receptors of the characteristic somatic (0) antigens has been discussed. It has been concluded that probably less than 2 × 103 molecules of antibody are required to sensitize the average S. typhosa O 901 cell to the bactericidal action of complement, and evidence has been presented which shows that this amount of antibody is probably less than one per cent of the total amount of antibody that can be taken up by cells of this strain.
Formation of the Particles of Influenza Virus
Authors: Wyckoff Ralph W. G.
Published: January 2023

Electron micrographs of chorioallantoic membranes of chicken embryos infected with influenza virus show particles having the dimensions of the particles seen in purified viral suspensions. These particles develop from, and are continuous with, the cytoplasm of the infected cells; they have not been observed forming within the bodies of intact cells.

Some particles of similar dimensions have been seen developing from certain cells of tissues inoculated with vaccinia and the Rous virus. This suggests that the cytoplasmic “fragmentation” that produces the virus particles of influenza may be in itself a nonspecific cellular response to an unfavorable environment. The bearing of these observations on the probable nature of the virus of influenza is discussed.
Effect of Thiosemicarbazones and Dichlorophenoxy Thiouracil on Multiplication of a Recently Isolated Strain of Variola-Vaccinia Virus in the Brain of the Mouse
Authors: Minton S. A. , Officer J. E. , Thompson R. L.
Published: January 2023

The antigenic and biological properties of the Williamsport virus place it in the variola-vaccinia group. It is highly infectious for mice and rabbits. Intracerebral injection in mice is followed by a gradual increase in the concentration of virus in the brain. After reaching a maximal value, the titer decreases. The limiting concentration of virus in the brain is independent of the amount injected. The rate of multiplication varies indirectly with the size of the inoculum. Death usually takes place when the viral content of the brain is greatest but may occur during the next 48 hours.

Thiosemicarbazones with antivaccinal activity protect mice against the Williamsport virus following intracerebral injection of the virus. The response is similar whether materials are fed in the diet or administered by the peritoneal route. Isatin and 5-nitro-2-thenaldehyde thiosemicarbazones protected the majority of mice when injected intraperitoneally within a period of 48 hours immediately after the inoculation of virus.

Protection of mice against Williamsport virus by treatment with isatin and other thiosemicarbazones is not associated with inhibition of viral proliferation in the brain. Dichlorophenoxy thiouracil may act in part by suppression of viral growth.
Effect of Heterocyclic and Other Thiosemicarbazones on Vaccinia Infection in the Mouse
Authors: Thompson R. L. , Minton S. A. , Officer J. E. , Hitchings G. H.
Published: January 2023

Thiosemicarbazones containing benzene, thiophene, pyridine, quinoline or isatin groups have been demonstrated to protect mice against vaccinia virus. Protection is obtained when the virus is given by the cerebral route and compounds fed in the diet.

The =N-NH-CS-NH2 group, as such, appears to be essential for antivaccinal activity. Semicarbazones of benzaldehyde, 2-thenaldehyde, cinchoninaldehyde and isatin were devoid of protective capacity.

The presence of an aldehyde structure with attachment of the thiosemicarbazone moiety to the aldehyde carbon atom contributes to antiviral capacity but is not essential for this property.

Substitutions on the aldehyde carbon atom reduced or abolished protective action of compounds. Substitution in the ring protion of the molecule produced the same result except in p-nitro and o-methoxy benzaldehyde and 5-chloro, 5-bromo and 3-methyl-2-thenaldehyde derivatives.

Thiosemicarbazones with high antivaccinal activity in mouse embryonic tissues may fail to protect mice against the virus.
Fractional Dilution Procedure for Precise Titration of Hemagglutinating Viruses and Hemagglutination-Inhibiting Antibodies
Authors: Horsfall Frank L. , Tamm Igor
Published: January 2023

A precise but relatively simple procedure for carrying out hemagglutination and hemagglutination-inhibition titrations with 5 viruses is described. In brief, the procedure is based on the use of a series of fractional dilutions of material under test in steps of 0.1 log unit. The method does not require any special equipment and yields titration endpoints which are closely reproducible. An analysis of the precision of the procedure relative to replicate titrations and the reproduction of absolute titers is presented. Both in hemagglutination and in hemagglutination-inhibition titrations, the precision of the results obtained with this technique is comparable to that yielded by photometric procedures.
A Note on the Use of the Antigen Excess Zone to Reveal the Existence of Certain Types of Cross Reactions in Unidentified Mixtures of Antigens
Authors: Cohn Melvin
Published: January 2023

Most single protein-antiprotein reactions are characterized by the marked solubility of the antigen-antibody complex in excess antigen (1) and the quantitative precipitin curves describing such a reaction decrease rapidly to zero in this region. There are a number of situations, however, in which the precipitation of specific complexes persists even far into antigen excess. For example, this situation may prevail when several unrelated systems react simultaneously (2, 3) or when a given antibody reacts with a mixture of homologous and heterologous antigens (4). It is the latter case which will concern us in the present paper.3

The reaction under consideration involves the β galactosidase (Gz) and a structurally similar protein (Pz) found in extracts of Escherichia coli. Active extracts from cells grown in the presence of an inducer, e.g., lactose, β-methyl-galactoside, contain both Gz and Pz while inactive extracts, from cells grown in the absence of an inducer of β-galactosidase contain Pz but not Gz.
Specific White Cell Lysis Produced by Combination of Rabbit Antiserum to Purified Protein (Ovalbumin, Bovine Gamma Globulin) with Homologous Antigen. The Role of Non-Precipitating Antibody
Authors: Waksman Byron H. , Gaulitz Donald
Published: January 2023

Specific white cell lysis is produced by the addition of homologous antigen to fresh heparinized blood of certain rabbits immunized with crystalline hen ovalbumin or with bovine gamma globulin (Armour's Fraction II). Specific lysis may be produced in white cells of fresh normal rabbit blood by the addition of antigen and the serum of a sensitized animal. There is an optimum concentration of antigen or range of antigen concentrations giving maximal lysis when the amount of antibody is constant. Dilution of antiserum results in a corresponding reduction in the amount of antigen producing maximal lysis and in a reduction of its lytic potency. Heating at 55–58 C for 4 hours failed to destroy the lytic capacity in 3 of 4 antisera tested. The cells affected by specific lysis were polymorphonuclear leukocytes in tests of 5 different antisera (platelets were not studied). The specific lytic capacity of an antiserum is not related to its content of precipitable antibody N or to its equivalence ratio R. No loss of lytic power results from removal of the precipitable antibody by small successive additions of antigen. Removal of all precipitable antibody by a single addition of antigen removed all lytic power from one of 2 sera so studied. Certain specifically lytic anti-ovalbumin sera showed lysis with an immunochemically uniform ovalbumin preparation and not with the common ovalbumin contaminants. These also showed a single band of precipitate by the Oudin agar diffusion technic, whereas certain nonlytic sera showed more than one band. White cell lytic power was moderately well correlated with the ability to give passively transferred urticarial reactions in human or guinea pig skin, but not with the ability to cause passive anaphylaxis in the guinea pig. Development of specifically lytic antibody was more evident in rabbits immunized by single intraperitoneal or intravenous doses of antigen in solution or repeated subcutaneous doses of alum-precipitated antigen than in rabbits receiving repeated subcutaneous or intravenous doses of antigen in solution.
The Comparative Retention of Antigen in the Skin of Immune and Normal Rabbits as Determined with Egg Albumin Labelled with Radioactive Iodine
Authors: Korngold Leonhard , Stahly Grant L. , Dodd Matt C. , Myers William G.
Published: January 2023

A radioactive antigen which emitted gamma rays was prepared by chemical attachment of radioactive iodine, I131, to crystallized hen egg albumin. The rates of disappearance of radioactivity from sites of injection were determined with a Geiger-Mueller counter shielded with lead to give directional collimation. The labelled antigen was specifically precipitated with antiiodinated ovalbumin serum as well as with anti-ovalbumin serum. An increased retention of radioactivity after intradermal injection of the iodinated ovalbumin persisted only in those rabbits which were sufficiently immune to iodinated ovalbumin to respond with a pronounced inflammatory (Arthus) reaction. Tracer radioactive albumin was also retained to a greater degree than in normal skin when injected into a site undergoing an Arthus reaction produced by the simultaneous injections of bovine gamma globulin into animals sensitized to this antigen. This increased retention of ovalbumin was interpreted as a non-specific effect of inflammation since no antiovalbumin was present.
Immunological Studies of Egg White Proteins
Authors: Wetter L. R. , Cohn Melvin , Deutsch H. F.
Published: January 2023

Conclusions and Summary

Evidence has been presented that many components of the egg whites of turkey, guinea hen, pheasant, duck and goose cross-react with antisera to chicken ovalbumin, conalbumin, ovomucoid, lysozyme and certain uncharacterized minor components.

Since Landsteiner and others (5) have clearly shown that the phenomenon of cross-reaction is due to the structural similarity of the combinants involved, a phylogenetic relationship between the various species possessing similar proteins is implied. Most studies based on this idea have been carried out using qualitative methods (19). The data presented here point out the type of results which can be expected from quantitative methods.
The Separation of Alpha Toxin (Lecithinase) from Filtrates of Clostridium Welchii
Authors: Roth Florence B. , Pillemer Louis
Published: January 2023

Discussion and Summary

Alpha toxin has been separated from filtrates of Cl. welchii type A by fractionation in methanol-water mixtures under controlled pH, ionic strength and temperature. By means of four fractionation steps, the toxin was purified 130 fold on the basis of Lb activity per mg of non-dialysable nitrogen.

Lecithinase combining activity, lethal activity, and alpha (hot-cold) hemolysin were found to be proportional in the four fractions, indicating that one substance may be responsible for all these activities. However, a homogeneous protein has not been isolated as yet, and conclusive proof that the three activities are functions of a single agent is still lacking.

The major contribution of the present study was the effective chemical separation of alpha from theta toxin. Earlier attempts to separate alpha from theta toxin by ultrafiltration (13) and ammonium sulfate fractionation (6) were unsuccessful. PIV #253 was highly lethal and the ratio of Lb to M.L.D. per mg N remained constant in both the filtrate and in PIV. This is additional evidence that alpha toxin and not theta is the lethal component of Cl. welchii type A infections.

It should be mentioned that purification studies were greatly retarded by low potency parent filtrates. It appears that much work remains to be done to produce filtrates rich in alpha toxin on a defined medium, if further progress is to be made in purification of the biologically and immunologically active components in Cl. welchii culture filtrates.
The In-Vitro Purification of Tissue Localizing Antibodies
Authors: Korngold Leonhard , Pressman David
Published: January 2023

The purification of antibodies in vitro was carried out by adsorbing radioiodinated anti-liver, anti-kidney, anti-lung and anti-spleen sera with a blood vessel fraction or cellular fraction of an organ and then eluting the adsorbed radio-activity by heat at 60°C.

It was found that the eluates obtained from blood vessel fractions of liver, kidney and lung had different localizing properties from the eluates of the cellular fractions of the same organs. It was also found that eluates could be prepared which would localize preferentially in either liver, kidney, lung or spleen by purifying the proper anti-tissue serum with a homologous tissue fraction. Antibodies from anti-lung, anti-liver and anti-spleen sera localized to the greatest concentration in the homologous organ when the purification was carried out with the cellular fractions of lung, liver and spleen respectively. With the anti-kidney serum the best results were obtained with the kidney blood vessel fraction.
Influence of Non-Specific Inhibitor on the Diagnostic Hemagglutination-Inhibition Test for Influenza
Authors: Hilleman M. R. , Werner Jacqueline H.
Published: January 2023

Human sera contained heat stable (56 C) nonspecific inhibitor for influenza A and B hemagglutinin but not for influenza C. This inhibitor appeared to be of the alpha type and was destroyed by treating with filtrate from cultures of Vibrio cholerae which were rich in Burnet's receptor destroying enzyme. This procedure did not have a demonstrable effect on antibody.

The PR8, FM1 and Lee strains of virus used in the Standard Hemagglutination-Inhibition Reference Test in Influenza Studies were highly sensitive to the alpha inhibitor. The inhibitor content for these and other strains often exceeded the amount of antibody. The reliability and sensitivity of the hemagglutination-inhibition technique for demonstrating antibody increase in paired serum specimens from cases of influenza and from vaccinated persons using the PR8, FM1, Lee and IB1 viruses was markedly improved by treating to remove inhibitor. This resulted primarily from the marked reduction in titer of the first serum specimen. The sensitivity of the test also depended on test virus; thus, the type A prime strains FM1 (1947) and FW-1-50 (1950) were superior to the 1934 PR8 agent for detecting infection with the A prime viruses of contemporary prevalence. The FW-1-50 virus was especially useful for diagnosis since it was essentially unaffected by the alpha inhibitor in human serum and the need for treatment with cholera filtrate was obviated.

The importance of removing non-specific inhibitor from sera tested to determine the basic antibody levels in the human population for the various influenza strains was discussed.
Chemical and Immunological Studies on a Heterophile Fraction Isolated from Bovine Erythrocyte Stroma
Authors: Markowitz Abraham , Simmonds Wayne L.
Published: January 2023

Chemical analysis of an extract obtained from bovine erythrocyte stroma revealed it to be of a proteinaceous nature. Nine amino acids were identified as lysine, glutamic acid, serine, glycine, threonine, alanine, aspartic acid, leucine and isoleucine from acid hydrolysates of the extract via paper chromatography. Electrophoretic determinations indicated the extract to contain four discernible portions, three of which carried a portion of the immunologic activity. Enzymatic hydrolysis of the extract with proteinases destroyed all immunologic activity.
Studies on Autoantibodies in Human Sera
Authors: Wiener Alexander S. , Gordon Eve B. , Gallop Carol
Published: January 2023

Evidence is presented for the existence in human sera of autoantibodies of different specificities. It is shown that cold autoantibodies parallel in their behavior the natural isoagglutinins, and therefore are probably directed against the nucleus of the A-B-O substance. The autoantibodies found in typical cases of acquired hemolytic anemia parallel the behavior of Rh-Hr antibodies, and are presumably directed against the nucleus of the Rh-Hr substance. A serum is also described containing an autoantibody which mimics the behavior of M-N antibodies, and therefore is presumably directed against the M-N-S substance. The possibility of the existence of autoantibodies of still other specificities must also be considered. The hypothesis presented here, while not fully established, is useful since it suggests new avenues of approach to the problem of autosensitization.
Allergic Encephalomyelitis in the Rat Induced by the Intracutaneous Injection of Central Nervous System Tissue and Adjuvants
Authors: Lipton Murray M. , Freund Jules
Published: January 2023

Allergic meningo-encephalomyelitis can be induced in the white rat by the intracutaneous injection of a suspension of brain or spinal cord combined with paraffin oil and killed mycobacteria. Constant symptoms are flaccid paralysis of the hind legs, urinary incontinence and fecal impaction. Remissions are frequent. Constant lesions are mild, focal, mononuclear meningitis, mononuclear cuffing of venules and capillaries of the brain and spinal cord. Glial nodules may occur. Compared on the basis of weight, spinal cord from the rat or guinea pig is about equally effective; rat brain and rabbit spinal cord are less effective. The presence of killed mycobacteria or Nocardia asteroides in the emulsion is essential for the production of the experimental disease. The intracutaneous injection of a suspension of 120 mg rat spinal cord and adjuvants induced encephalitis regularly, whereas the subcutaneous injection of the same material was without effect. Rat spinal cord combined with adjuvants injected intracutaneously causes encephalitis in the guinea pig.