bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Environmental Temperature on the Reaction of Mice to Tetanus Toxin
Authors: Ipsen Johannes
Published: January 2023

In two consecutive summer weeks, pronounced differences in survival time were noted for mice subjected to identical doses of tetanus toxin. Room temperatures at the time of the two observations were 25 C and 35 C, respectively (Experiments 2 and 3, Table IV). Survival times are ordinarily reproducible when the same dose is used. One possible explanation of the observed differences was the environmental temperature. Variation in inherent susceptibility between two lots of mice rarely causes such differences, as judged by experience with mice from the same laboratory stock (4), or from different laboratories in various parts of the world (6).

The effect of environmental temperature on resistance to infection has been studied experimentally through temporary chilling (2) of animals subjected to fixed doses of a pathogenic agent (5). Momentary exposure of infected animals to extreme variations in temperature is seemingly less comparable to natural conditions than where experimental animals are maintained at uniform raised or lowered temperatures that are consistent with the survival of normal animals.
Relationship between Treponemal Immobilizing Antibodies and Acquired Immunity in Experimental Syphilis
Authors: Magnuson Harold J. , Thompson Frederick A. , McLeod Charlotte P.
Published: January 2023

Measurement of circulating “immobilizing antibody” has proved to be a poor measure of the resistance of immune rabbits to challenge infection with three strains of Treponema pallidum. Crude correlation between the results of the immobilization test and the resistance to challenge was demonstrated only when challenge shortly followed termination of the immunizing infection. Strain 20A may be a more sensitive antigen than the Nichols strain of Treponema pallidum in the demonstration of the immobilization phenomenon. The in vitro immobilization test failed to demonstrate strain differences among three strains of T. pallidum. The mechanism of acquired immunity in syphilis is still poorly understood.
The Size of Coxsackie Viruses and Lansing Poliomyelitis Virus Determined by Sedimentation and Ultrafiltration
Authors: Melnick Joseph L. , Rhian Morris , Warren Joel , Breese Sydney S.
Published: January 2023

The sizes of 6 members of the Coxsackie, or C, group of viruses, representing 4 antigenic types, have been determined by filtration through gradocol membranes and by sedimentation in the ultracentrifuge. Filtration end points and sedimentation constants were measured by following the activity of the infectious particles.

The Conn.-5, Ohio-1, High Point, and Texas-1 C viruses and the Lansing poliomyelitis virus are of comparable size: 15 to 23 mμ according to filtration data and approximately 24 to 32 mμ from sedimentation data. By optical analysis in the sector cell of the ultracentrifuge, the purified Texas-1 strain yielded a value of about 33 mμ. These results are also in agreement with those found by electron microscopy of purified Texas-1 strain.

The TT strain (Type 1) yielded a value of 7 to 10 mμ from the filtration experiments and of about 27 mμ from the sedimentation data.

The complement fixing antigen was found to sediment at about the same rate as the infectious particle for the High Point strain.
The Production of Antibody by Patients with Chronic Hepatic Disease
Authors: Havens W. Paul , Shaffer James M. , Hopke Charles J. , Eichman Hazel L. , Williams W. Ruth
Published: January 2023

The amounts of antitoxin produced by 27 Schick-negative patients with chronic hepatic disease and 36 Schick-negative patients with other acute and chronic diseases following the intramuscular injection of 50 Lf purified diphtheria toxoid were measured by titration in the skin of rabbits. When the maximum measured amounts of antitoxin were compared, the patients with chronic hepatic disease were found to have made, on the average, three times as much antibody as the controls. There was no apparent relationship between the amounts of antitoxin produced and the age, clinical condition, degree of malnutrition, amounts and partition of serum proteins, and resistance to intercurrent infections. The synthesis of antibody appeared to be a highly preferential function resulting in certain cases in a replacement of a large percentage of the globulin previously present. On occasion, it appeared to be operative at the expense of the production of serum albumin.
Studies on Immunization Against Plague
Authors: Chen T. H. , Quan S. F. , Meyer K. F.
Published: January 2023

A procedure for the complement-fixation test with plague Fraction I as antigen and specific high-titered antiplague (by preference anti-Fraction I) serum as antiserum has been described.

Examples of the use of the method are given: the determination of Fraction I plague antigen in the bacteria and in tissue extracts of carcasses of mice and guinea pigs that had died of experimental plague. Antibodies to Fraction I were detected in convalescent human sera, in sera of guinea pigs immunized with various living avirulent plague organisms, and of rabbits and monkeys immunized with Fraction I. The titers obtained are in direct agreement with values determined by precipitation, agglutination, immunization and passive mouse-protection tests.

The complement-fixation tests, besides being a valuable addition to research plague studies, also acts as a liaison test for evaluation of plague vaccines, estimation of degree of immunity, determination of potency of antiplague sera, confirmation of recent infection with Pasteurella pestis and help in the positive identification of plague bacilli.
The Interchangeability of the Complement Components of Different Animal Species
Authors: Rice Christine E. , Boulanger Paul
Published: January 2023

Horse, cow, and sheep complements, all three of which are “non-hemolytic” for sheep red cells sensitized with specific rabbit antiserum, were found to be hemolytic for rabbit red cells, either untreated or sensitized with specific sheep antiserum. Hence, a sensitized rabbit-red-cell suspension was used as the indicator in the titration of complement in fresh sera of these three species. The titers obtained differed significantly from these determined with the “standard” hemolytic indicator or by conglutination.

Dialysis in the cold in phosphate buffer of pH 5.4 and ionic strength 0.02, separated these complements into insoluble and soluble fractions that were inactive alone but which on admixture showed hemolytic properties for sensitized rabbit-red-cells. Treatment with zymosan or hydrazine in suitable amounts inactivated each of these complements; the hemolytic activity was restored by the addition of heated serum of the same and of certain other species.

Titrations of hemolytic activity for sensitized rabbit-red-cells suggest therefore that the complements of the horse, sheep, and cow, like those of the other complements previously studied, consist of a complex of four major components, which it seems reasonable to designate as C′1, C′2, C′3 and C′4, although, owing to some species incompatibility they may not always prove mutually interchangeable with the corresponding complement components of the guinea-pig or other animals.
Studies of a “Complete” and an “Incomplete” Rh Antiserum with cDe/cde and -D-/-D- Cells
Authors: Sturgeon Phillip , Brown Raymond A. , Stettner Constance E.
Published: January 2023

Summary and Conclusions

Fractions of an Rh antiserum prepared by electrophoresis-convection and titrated with cDe/cde cells revealed no saline agglutination, but incomplete antibodies including saline blocking antibodies were found in high titers. Tests of these fractions with -D-/-D- cells, however, did reveal the presence of saline agglutinins in 5 out of 7 fractions; nevertheless, prozones (up to 1/4 dilution) in the saline agglutination titrations were present, blocking in saline occurred in a low dilution (1/2) of one of the fractions, and incomplete (albumin agglutination and indirect antiglobulin titrations) resulted in endpoints from 16 to 64 times higher than the saline agglutination titers.

The results of this study, therefore, substantiate those of the previous report, which indicated that incomplete antibodies do not react as bivalent (complete or agglutinating antibodies) with -D-/-D- cells. They also indicate that saline agglutination of -D-/-D- cells can be blocked by incomplete antibodies, and that fractions of Rh antisera (as well as native sera) which appear to contain only incomplete antibodies may show the presence of complete antibodies if tested with -D-/-D- cells.
Intranuclear Inclusion Bodies in Cultures of Human Tissue Inoculated with Varicella Vesicle Fluid
Authors: Weller Thomas H. , Stoddard Marguerite B.
Published: January 2023

Following the inoculation of varicella vesicle fluid into suspended cell cultures of human embryonic tissues, eosinophilic intranuclear inclusion bodies were demonstrable in six different experiments. The evidence suggested that the inclusion bodies were induced by the action of varicella virus. No intranuclear inclusions could be demonstrated in subcultures.
Blood Group Activity and Composition of Polysaccharides from Pancreatins
Authors: Verney Ethel , Stock Aaron H.
Published: January 2023

A commercial pancreatin contained a polysaccharide with blood group A activity which was similar in composition to other serologically active tissue polysaccharides. A second commercial pancreatin yielded a serologically inactive polysaccharide that appeared to be degraded chemically.
Studies on Herpes Simplex Virus
Authors: Jawetz Ernest , Allende M. F. , Coleman Virginia R.
Published: January 2023

When examined by an egg-neutralization technique which employed preliminary incubation of virus-serum mixtures (1 hour at 37 C) human sera failed to exhibit “all or none” character of herpes antibody levels. The antibody titers of sera from herpetic individuals extended over more than a one thousandfold range.

Significant fluctuation in herpes antibody titer was demonstrated in sera obtained from such individuals at different times.
The Antigen-Antibody Reaction
Authors: Aladjem Frederick , Lieberman Mirjam
Published: January 2023

A quantitative study of the precipitin reaction has been made as a function of NaCl concentration. The system used was chicken ovalbumin and the homologous rabbit antibody separated into its eu- and pseudoglobulin fractions and the same antibody fractions and duck ovalbumin as the heterologous system. Using pseudoglobulin antibody, it was shown that in the virtual absence of salt the precipitin reaction not only persists but gives larger amounts of precipitate N in the equivalence and antigen excess zones than when NaCl was added. Furthermore, antigen excess inhibition occurs at much lower antigen concentrations in 9.0 and 0.9% than in 0.09% NaCl. In the 0.00% NaCl series about seven times the antigen N concentration of the equivalence zone is needed for partial inhibition, compared with about twice the equivalence zone antigen N needed for almost complete inhibition with 0.9% NaCl. Some of the possible causes for these differences are discussed. It is suggested and evidence is presented that rabbit pseudoglobulin antibody may contain at least two antibody fractions. One of these precipitates preferentially at the lowest sodium chloride concentration and only to a very small extent in 0.9% or higher salt concentration. For want of further defining criteria this fraction is tentatively called “salt sensitive” antibody. The rest of the pseudoglobulin antibody appears to be much less “salt sensitive.” In the precipitin reaction with euglobulin antibody less nitrogen is precipitated throughout the course of the reaction at the higher salt concentration than at the lower salt concentration. The heterologous reaction between duck ovalbumin and eu- and pseudoglobulin antibody fractions differs somewhat from the homologous reaction. Decreased amounts of precipitation, greater inhibition of the reaction at the higher salt concentrations, and less inhibition in antigen excess were observed.
Quantitative Aspects of Influenza Virus Multiplication
Authors: Cairns H. J. F.
Published: January 2023

The multiplication of influenza virus in the cells of the allantois and the resulting increase of virus in the allantoic fluid have been shown repeatedly to be logarithmic (24, 25, 26). This steady exponential increase is presumed to be the result of a succession of multiplication cycles with a constant multiplication factor (“cyclic increment”) and of constant duration (“cycle time”); as the cycles gradually merge into each other the growth process, having been discontinuous in its early stages, becomes approximately logarithmic in its later stages. For the increase of influenza A viruses in the allantoic fluid, the average increment was estimated in Henle's one-step growth experiments (17, 27) to be between 50 and 100. The same experiments showed that liberation of newly formed virus began after a constant period of 5 to 6 hours, although the average time for liberation, namely the time at which half the ultimate first-cycle yield of virus had been liberated, appeared to be about 8 hours.
The Effect of ACTH and Cortisone on the Quantitative Precipitin Reaction
Authors: Malkiel Saul , Hargis Betty Jean
Published: January 2023

Rabbits were treated with ACTH and cortisone given in physiologically significant doses prior to and during the period of immunization with bovine serum albumin. The behavior of the reaction between the antigen and the antibodies thus engendered as studied by the quantitative precipitin technic was not inconsistent with that from control animals. ACTH caused a marked diminution of the antibody titer and cortisone an almost complete suppression.
Toxicity of NDV for Mouse Lungs
Authors: Davenport Fred M.
Published: January 2023

The toxicity of NDV, as measured in mouse lungs, has been described. It has been shown that pulmonary consolidation and death follow the intranasal instillation of large doses of virus and that these effects are caused by the virus, rather than by nonviral components of the inoculum. The gross and microscopic appearance of the lung lesions has been described. The pulmonary toxicity of NDV suspensions is abolished by procedures which destroy the property of infectivity for eggs and is neutralized by specific immune serum. After intranasal instillation, NDV appears to be rapidly adsorbed on lung tissue, and the toxic reaction cannot be suppressed by immune serum given promptly by the same route. Attempts to protect mice by vaccination either by the intraperitoneal or intranasal route were unsuccessful, although vaccinated mice develop antibodies capable of neutralizing the toxicity of virus suspensions in vitro. Multiplication of NDV virus in mouse lungs cannot be demonstrated even though measurements of the concentration of virus in lungs are made at frequent intervals. An hypothesis which might explain the mechanism of cell injury in virus infections, as well as in toxic reactions, has been formulated, and some of its implications were discussed.
Studies on Immunization Against Plague
Authors: Chen T. H.
Published: January 2023

Conclusions and Summary

A hemagglutination test has been developed for P. pestis. The antigen is contained in old broth cultures, in extracts of killed and dried organisms and in alcohol-precipitated envelope antigens, but not in the protein fractions soluble in 0.25 saturation of ammonium sulfate solution or in those isolated by precipitation of soluble extracts by 0.3 or more saturated ammonium sulfate. The crude antigen has a low nitrogen content and is likely to be a polysaccharide.

The use of the hemagglutination test or of the inhibition of hemagglutination may be valuable in ascertaining the identity of plague antigens. The hemagglutination antigen appears not to play an important role as a protective antigen in plague.
Involvement of a Complement-Like Factor in the Activation of Blood Protease
Authors: Geiger Walton B.
Published: January 2023

The activation of the protease of blood serum or plasma by streptococcal fibrinolysin requires the presence of both a heat-stable and a heat-labile factor. The heat-stable factor is demonstrable in heated human serum, plasma, milk, colostrum, and saliva. Cows' milk and colostrum also contain the factor. Useful sources of the heat-labile factor include guinea-pig serum, rabbit plasma, duck serum, and chicken serum. The activation of blood protease by streptococcal fibrinolysin is prevented by many reagents that remove or destroy midpiece of complement. Calcium ions seem to be required for the activation.
Immunological Studies on Types of Diphtheria Bacilli
Authors: Park William H. , Williams Anna W. , Mann Alice G.
Published: January 2023

The subject of this communication would have been exhaustively investigated long ago if there had been practical evidence that a monovalent diphtheria antitoxin did not protect from diphtheria. It is true that in regard to B. tetani and B. botulinus laboratory investigations have given contradictory results as to the efficacy of a monovalent serum. These investigations have shown us: first, that tetanus bacilli, although they are divided into several types by their response to agglutinins, nevertheless, all produce toxins which are neutralized by a monovalent antitoxin; second, that the reverse is true of the bacilli causing botulism, in so far as the production of toxin is concerned. Among the strains of B. botulinus there are at least two different types producing toxins which respond only to homologous antitoxins.

As to diphtheria bacilli, however, there are two series of observations which have been made concerning the degree of protection afforded by monovalent diphtheria antitoxin.
On the Origin and Nature of Alexin (Complement) in Guinea-Pig Blood
Authors: Morrison L. F.
Published: January 2023

Nomenclature has always played an important rôle in scientific literature. The accepted ethics of terminology recognize and uphold the precedence of priority in cases of dispute providing that the earlier investigator fully describes the substance in question. Owing to individual idiosyncrasies this procedure, in some instances, has been disregarded and serious confusion and controversy has arisen.

Nuttal (1), von Fodor (2) and others recognized and experimentally demonstrated the presence of a bactericidal substance in fresh blood and blood serum but failed to attribute a name to the substance. Buchner (3), in 1889, gave the name of “alexin” to this thermolable, bactericidal, ferment-like, protecting substance. Bordet (4) later verified the presence of this substance and recognized the accuracy of the word “alexin.” In addition he discovered the thermostable factor, which also takes an important part in this reaction.
Natural Pathogenicity of Mumps Virus for Suckling Hamsters on Intracerebral Inoculation
Authors: Kilham Lawrence , Overman John R.
Published: January 2023

Mumps virus has been found to produce fatal encephalitis of suckling hamsters, signs of illness appearing 8 to 9 days after inoculation. The peak of the virus growth appears several days before clinical illness becomes manifest. Evidence is presented that mumps virus, freshly isolated from the human host, may have natural pathogenicity for suckling hamsters. Primary isolation of virus from a sample of human milk known to contain the agent, has been accomplished on first passage in suckling hamster brain. With death as a sharp endpoint, suckling hamsters make satisfactory animals for the performance of serum neutralization tests.
The Effects of Spleen Shielding and Subsequent Splenectomy upon Antibody Formation in Rats Receiving Total-Body X-Irradiation
Authors: Wissler R. W. , Robson M. J. , Fitch F. , Nelson W. , Jacobson L. O.
Published: January 2023

Total body X-irradiation has been shown to cause a marked depression of humoral antibody formation in response to a single injection of antigen given shortly after irradiation (1–8). In previously reported studies in the rabbit, Jacobson et al. have demonstrated that lead shielding of the spleen during total body irradiation will largely prevent this reduction of circulating antibody concentration. Furthermore, these investigators have found that if the shielded spleen is left in the animal for only 24 hours after irradiation but is removed 24 hours before intravenous antigen is given there is still striking protection of the antibody forming mechanism (6). Therefore, in the 24 hours following exposure to X irradiation the shielded rabbit's spleen apparently releases a humoral or cellular product which protects or allows very quick recovery of the remaining irradiated antibody forming tissues of the body.
The Altered Reactivity of Mice after Immunization with Hemophilus Pertussis Vaccine
Authors: Kind Leon S.
Published: January 2023

Pertussis-inoculated young mice were more resistant to the lethal effects of histamine than pertussis-inoculated older mice similarly challenged.

Phase IV H. pertussis vaccine did not sensitize mice to the lethal effects of histamine.

Doses of E. coli and Sh. dysenteriae vaccines comparable in toxicity for normal mice to doses of Phase I H. pertussis vaccine also did not sensitize mice to histamine.

Mice rendered histamine-sensitive by injections of triple vaccine were no more susceptible to challenge doses of diphtheria or tetanus toxoids than mice previously inoculated with diphtheria or tetanus toxoids and shown to be histamine-resistant.

However, histamine-sensitive mice were demonstrated to be more susceptible to passive anaphylaxis than histamine-resistant mice.

Inoculation of mice with H. pertussis vaccine sensitized the animals to the lethal effects of H. pertussis, E. coli, and Sh. dysenteriae vaccines. However, the inoculation of mice with E. coli or Sh. dysenteriae vaccine did not increase the susceptibility of the animals to E. coli, Sh. dysenteriae or H. pertussis vaccine.

After pertussis inoculation, the sensitivity of mice to histamine and to H. pertussis vaccine ran a parallel course.

The possible relationship between the sensitivity of pertussis-injected mice to histamine and to H. pertussis vaccine is discussed.

It is suggested that pertussis vaccine may sensitize mice to histamine and to pertussis vaccine by damaging the adrenal gland.
Bovine Erythrocyte Antigens
Authors: Lazear E. J. , Ferguson L. C.
Published: January 2023

Conclusions and Summary

The following conclusions have been reached from the data presented: The temperature to which the serum-cell mixture was exposed had little effect upon the rate of antibody absorption. However, extreme temperatures above and below room temperature usually reduced the homologous titer with little or no effect upon the heterologous titer.The optimal absorption time was approximately 30 minutes. After this time the homologous and heterologous titers tended to level off and closely parallel each other.The optimal cell volume was dependent upon the serum used. In no case was the volume greater than 50% when the optimal dilution of serum and optimal time and temperature were used in the absorption. It is advisable to keep the cell volume to a minimum.The optimal dilution for each serum was dependent upon the complexity of the serum and the respective titers for the homologous and absorbing bloods. As a general rule, dividing the titer for the absorbing blood by 8 gives a dilution of serum satisfactory for absorption.
The Effect of the Injection of Tetanus Toxin into the Central Nervous System of Rabbits
Authors: Wright Eric A.
Published: January 2023

Tetanus toxin injected into the medulla oblongata of rabbits is approximately 1000 times as effective (measured by the period of survival) as toxin injected intravenously. The effectiveness of the injected toxin is progressively less as the following sites are employed—lumbar cord; cerebrospinal fluid and cerebral hemisphere (approximately equal); blood stream and gastrocnemius muscle.
A Preliminary Report on the Purification of Foot-and-Mouth Disease Virus by Serological Methods
Authors: Heckly Robert J.
Published: January 2023

Repeated injections of a fraction from normal bovine tongue epithelium into rabbits elicited the production of precipitins. It was observed that most of the infectivity of purified virus preparations was also precipitated by the antiserum to normal bovine tissue. Quantitative precipitin tests indicated that at least 90% of the most highly purified virus preparation tested consisted of material serologically indistinguishable from normal host tissue. Virus produced in guinea pigs did not react with the antiserum. Although mixtures of normal bovine tissue antigen and guinea pig virus gave comparable serological precipitates, most of the infectivity of the guinea pig virus remained in the supernatant serum. The results suggest that foot-and-mouth disease virus may possess certain serological characteristics of the host in which it was produced.
Studies on the Specific Soluble Proteins of Pasteurella Pestis and P. Pseudotuberculosis
Authors: Seal S. C.
Published: January 2023

Summary and Conclusions

A complement fixation test has been employed in the study of the specific protein fractions of the virulent and avirulent plague and pseudotuberculosis strains in the elucidation of the antigenic structure of these organisms. The P⅓ fraction of the soluble proteins of virulent and protective plague strains grown in enriched casein hydrolysate broth specifically fixes the complement, no cross-reactions being observed with the antisera against either the protein fraction or the whole of the avirulent nonprotective plague or pseudotuberculosis organisms.

The test confirms the findings of other serological tests, viz. precipitation and agglutination, carried out with these protein fractions or their antisera. The water-extractable fraction of a virulent plague strain is the most specific antigen found, but the tests fails to distinguish between the virulent and the relatively avirulent protective strains and a comparatively larger dose is required for mouse protection.

Antigenic deterioration of plague strains can be detected by cross complement fixation tests.

Antisera against pseudotuberculosis strains have given divergent results amongst themselves and further work with their protein fractions is indicated.

Antiplague rabbit sera are preferable to anti-plague horse sera for the complement fixation test.

The immunogenic values of the protein fractions and of whole vaccines prepared from various plague and pseudotuberculosis strains, have been determined. The results confirm the serological findings. Three categories of plague strains can be distinguished, viz., (1) virulent protective, (2) avirulent protective and (3) avirulent non-protective, the pseudotuberculosis strains falling under the last group.

The protective power of the Haffkine plague vaccine lies in the protein fractions of its supernatant. The P⅓ fraction (antigen A) of the first or the second group of organisms is fully responsible for the mouse protection given by the vaccine. Its immunogenic values seem to depend on the quality of the medium used. The corresponding P½-⅓ fraction (antigen B), on the other hand, gives practically no protection, even in heavy doses, but further work is needed to confirm this observation. The results of mouse-protection tests with the anti-protein sera support the above findings.

Certain future lines of studies on plague have been indicated, including the possibility of replacing with advantage the whole vaccine by the P½ fraction for human immunization.
Performance of Mumps Neutralization Tests in Suckling Mice
Authors: Kilham Lawrence , Murphy Helen W. , Overman John R.
Published: January 2023

The virulence of a mouse-adapted strain of mumps virus has been increased so that it will kill nearly 100% of suckling mice 1 day of age. This virus has been successfully used in intracerebral neutralization tests. The titers of neutralizing antibodies obtained for human and animal mumps immune sera were considerably higher than those obtained in egg neutralization tests. Differences between egg and mouse neutralizations are discussed.
Sulfur Mustard-Inactivated Influenza Virus as Interfering Agent
Authors: Fong Jacob
Published: January 2023

Discussion and Summary

One of the more favorable systems in studies of the interference phenomenon involves utilization of inactivated influenza viruses as interfering agent followed by a challenge dose of active homologous or heterologous virus. A common method for preparing interfering suspensions requires heating of virus (either as infected allantoic fluid or after dilution of virus in citrate-borate buffer of pH 8.5) at 56 C for one hour. The simplicity of this procedure is highly desirable, but not all strains of influenza viruses are of equal susceptibility in this respect. As reported herein, temperatures causing complete destruction of the infective component(s) of the two relatively heat-resistant strains of viruses under consideration also resulted in a striking reduction of the interfering quality. Apparently variations in heat resistance of influenza viruses are not necessarily accompanied by a corresponding variability in their interfering capacities.

The use of sulfur mustard in preparing inactivated but interfering suspensions of virus was suggested by previous studies of the action of mustards upon influenza virus (9, 10). Virus treated in this manner retained much of its interfering capacity. Prior injections of 128 agglutinating doses of inactivated virus resulted in more or less complete interference with the development of 100 ID50 of homologous challenge virus. With 256 agglutinating doses, injection of challenge virus before interfering virus produced only a minor change in the interfering potential of mustard-inactivated virus. A prior injection of 512 agglutinating doses of inactivated virus proved ineffectual against 107 ID50 of challenge virus, but partial interference was manifested against 103 to 105 ID50 of virus.

Studies of the effects of minor variations in concentration of sulfur mustard have demonstrated that it is better to err in the direction of a slight excess of mustard since lower concentrations of chemical (4 × 10-3 M) may result in incomplete destruction of virus. Despite the somewhat greater destruction of the interfering components of virus by 6 × 10-3 M mustard, a satisfactory interfering preparation was attainable.

While comparative tests with ultraviolet irradiated virus were not made, the simplicity and ease of control inherent in mustard inactivation of virus is lacking in the former. The relative stability of refrigerated samples of interfering virus prepared with sulfur mustard is of advantage. Preliminary tests on the infective and interfering capacities of the preparation may be made, and experimentation with a single batch of interfering virus is rendered possible. A specific though probably minor limitation of mustard-inactivated virus is related to the retention of viral enzymatic activity (10). This limitation, however, has not impaired its usefulness in our studies of the interference phenomenon which are reported in another paper.
The Effect of Antigen Administration on the Behavior of I131 Labelled Rabbit Anti-Ovalbumin in Mice
Authors: Masouredis S. P. , Melcher L. R. , Shimkin M. B. , Miller Patricia
Published: January 2023

A considerable literature has developed on the use of I131 trace-iodinated rabbit antibodies as indicators for the in vivo detection of antigenic proteins (1–6). The criterion employed in these studies has been the demonstration of selective localization of radioactivity in tissues as determined by radioautography and tissue radioactivity. Quantitative evaluation of results obtained with these methods are limited (7, 8), and the techniques in common use are capable of providing only a semiquantitative estimation of the antigen-antibody reaction. Interpretation of such data is also complicated by the inability to ascertain the contribution of labelled protein within the vascular space of a tissue to the total radioactivity determined in that tissue.

In the present report a metabolic balance study of radioactivity introduced as an I131 trace-labelled antibody was applied to the problem of in vivo antigen-antibody reactions using I131 rabbit antibodies in mice.
The Persistence of Complement in Aged Sera
Authors: Maurer Paul H. , Weigle William
Published: January 2023

Summary and Conclusions

It has been demonstrated that nitrogen which can fix to specific precipitates persists in rabbit, human, and guinea pig sera for long periods of time. The reasons for regarding this as complement nitrogen are discussed. The persistence of complement nitrogen is greatest in rabbit serum. Only rabbit complement affected the precipitation of soluble rabbit antigen-antibody complexes. It has been postulated that the effect of an anticomplementary substance present in sera decreases with age, dilution, and increase in temperature. The effect of versene on the contribution of complement nitrogen to specific precipitates by guinea pig and some human sera has been confirmed. However, versene in the concentrations used had no effect on the complement of rabbit serum.
The Requirement for Magnesium Ions in the Inactivation of the Third Component of Human Complement (C′3) by Insoluble Residues of Yeast Cells (Zymosan)
Authors: Pillemer Louis , Blum Livia , Pensky Jack , Lepow I. H.
Published: January 2023

Mg++ is required for the inactivation of C′3 by insoluble residues of yeast cells (zymosan). The concentration of Mg++ in normal serum is more than adequate for the reaction to proceed optimally. The requirement for Mg++ is also demonstrated by the greater uptake of serum nitrogen by zymosan in the presence of Mg++ than in its absence.

The inactivation of human C′3 by zymosan appears to be a stoichiometric reaction sharply dependent on temperature, ionic strength and pH. The optimum conditions are at 37 C, ionic strength 0.15 or less, and pH 6.8–8.6.

The complex formed upon the addition of zymosan to serum is highly undissociable or results in the destruction of C′3 activity. Attempts to elute C′3 from the zymosan complex were unsuccessful.
Studies on the Role of Ca++ and Mg++ in Complement Fixation and Immune Hemolysis
Authors: Levine Lawrence , Cowan Keith M. , Osler Abraham G. , Mayer Manfred M.
Published: January 2023

By means of quantitative precipitin analyses, it has been shown that EDTA inhibits the capacity of specific precipitates to take up the combining component or components of C′ from fresh guinea pig and human sera. In accord with this finding based on weight determination, the hemolytic activity of C′ is not removed by specific precipitates in the presence of EDTA. Ca++ and Mg++, as well as Co++, reverse the inhibition of C′ fixation by EDTA. These results suggest the Ca++ and/or Mg++ are essential for C′ fixation.
Studies on Herpes Simplex Virus
Authors: Geller P. , Coleman V. R. , Jawetz E.
Published: January 2023

A viable egg-adapted strain of herpes simplex virus was injected intravenously in large amounts in 11 human volunteers and attempts were made at various intervals thereafter to recover the virus from the blood by inoculation into fertile eggs. No significant amount of virus could be recovered by any method employed.

The small amount of virus which was recovered after inoculation onto the chorioallantoic membrane could not be transmitted by serial passage in ovo.

A complement-like heat labile substance was demonstrated in the plasma of one patient which inhibited the propagation of herpes virus in ovo.

Neutralization tests performed on sera obtained from the individuals prior to the virus injection demonstrated marked differences in titer of neutralizing antibodies to herpes virus. In contrast to the previous findings that the antibody titer did not change after injection of inactivated herpes virus, the intravenous injection of viable virus resulted in significant rises in neutralizing antibody levels in 4 out of 9 persons. The role of antibody, the heat labile plasma factor and viral removal mechanisms is discussed.

Egg-adapted strains of herpes virus failed to exhibit hemagglutination activity when tested in vitro against a wide variety of animal red blood cells, in contrast to the claims of Moolton et al.
Phosphatase-Antiphosphatase Reaction
Authors: Sevag M. G. , Newcomb Melva Derrick , Miller Ruth E.
Published: January 2023

Inhibition of the α-glycerophosphatase activity of intact dried yeast by specific antiserum produced in the rabbit indicates that the enzyme is located on the surface of the cells. Although easily extracted with water, its activity was manifested as an integral cellular component. Live yeast was phosphatase-inactive until air-dried but capable of inciting the production of antiphosphatase antibody in the rabbit.

Antiserum against the partially purified yeast α-glycerophosphatase inhibits the hydrolysis of α-glycerophosphate by the enzyme. The degree of inhibition is dependent upon the concentration of substrate and antiserum, respectively. The data show that the specific substrate, α-glycerophosphate, competes with antiphosphatase antibody for the specific active combining sites in the enzymes. The theoretical implications of these findings are discussed.
The Genetic Control of Response to Antigenic Stimuli
Authors: Sang J. H. , Sobey W. R.
Published: January 2023

The level of secondary antibody response to Tobacco Mosaic Virus (T.M.V.) is shown to be a highly heritable characteristic (h2 = 0.876, σ = 0.09) in a cross-bred population of rabbits. The secondary response to Bovine Plasma Albumin (B.P.A.) does not show any such heritability; variation as measured under our experimental conditions could all be assigned to environmental differences. However, diffusion tests demonstrate that this antigen has at least 7 reactive components, 2 of which are due to a globulin contaminant. In these circumstances, it is suggested that the “experimental error” deriving from the complexity of the antigen make any estimation of heritability impossible. A proportion of the rabbit population showed no response to B.P.A., even when given in massive doses. This failure to produce antibodies is probably due to a recessive gene (or genes) segregating in the population. Animals of this genotype retain the antigen in their circulation for an abnormally long time. Response in normal animals follows immediately on the disappearance of circulating antigen, but this reaction apparently does not occur in the abnormal group. Response to the other antigens tested, except possibly to globulins, was not affected by this “genetic block”. Correlations were found between response to T.M.V. and Diphtheria toxoid (D.t.) (r = 0.5, σ = 0.15) and to T.M.V. and Bovine Red Cells (r = 0.54, σ = 0.24). No correlations could be demonstrated for responses to Shigella Shiga, Bushy Stunt Virus, Human Red Cells, or Tetanus toxoid (T.t.) But the complex nature of these antigens makes this negative evidence inconclusive. Rabbits tested with all these antigens showed a significant tendency to produce related responses to different antigens, suggesting that they have a general predisposition to respond at some inherent level to all antigenic stimuli. Primary and secondary responses to D.t. are shown to be correlated, as are primary responses to D.t. and to T.t. Pregnant or lactating rabbits show a significantly lowered response to D.t. and to T.t. The importance of genetic constitution in determining ability to produce antibodies is discussed, and some of the necessary conditions for further work on this subject are defined.
The Hemagglutination Test for Rheumatoid Arthritis
Authors: Heller George , Jacobson Abraham S. , Kolodny Maxwell H. , Kammerer William H.
Published: January 2023

Two serological reactions have been described. The first reaction involves the inhibition of the hemagglutination test for rheumatoid arthritis by including human plasma Fraction II as a reagent. In the second reaction, the serum from individuals with active peripheral rheumatoid arthritis specifically agglutinated tannic acid-treated sheep erythrocytes sensitized with Fraction II. The heterogenic relationship of the reactants involved as well as the antigen-antibody-like character of these reactions are discussed.
Studies on the Complement Function
Authors: Silverstein Arthur M.
Published: January 2023

The fixability of guinea pig complement was found to be quite different from that of human C. The observed antibody titer of an immune serum may be raised or lowered by employing for the fixation test one of the several modified C reagents in admixture with normal C. Alterations of normal C component ratios produce C solutions which are quantitatively identical in hemolytic potency but qualitatively different in fixation to an immune complex. A non-additivity of C hemolytic potency units exists under the conditions of partial fixation to a immune complex, and is a function of the extent of that fixation. The unit of hemolytic activity measured before fixation seems to be different from that measured afterward, indicating the necessity to examine more deeply the exact functions of C components in fixation and hemolysis. The addition of increasing amounts of three C components for the estimation of the “titer” of the remaining component results in a continual increase in titer, never quite reaching the limiting asymptotic value. Hemolytic activity would appear to be a function of the active concentrations of all of the components, not only of that component present in “limiting amounts” as postulated previously.
Serological Aspects of the Suppression of Normal Bactericidal Action of Rabbit Serum Following Whole Body X-Irradiation
Authors: Donaldson David M. , Marcus Stanley
Published: January 2023

The loss or suppression of the normal bactericidal activity of rabbit serum following 650 to 725 r of whole body x-irradiation was not demonstrated to be due to a substance in the sera of irradiated rabbits which inhibits normal bactericidal activity. No decrease in the bactericidal action of normal serum was observed following the addition of serum from x-irradiated rabbits to normal serum. Titrations were carried out with sera from nonimmunized x-irradiated and control rabbits to determine natural agglutinin levels. Suspensions of sheep red blood cells and Bacillus subtilis were employed as antigens. The amount of circulating natural agglutinin was not significantly altered in the sera of x-irradiated rabbits with suppressed bactericidal activity. Complement concentrations determined at a time when the sera from irradiated rabbits showed suppressed bactericidal activity were of the same magnitude in x-irradiated and control rabbits. Addition of either E or M fractions of guinea pig complement failed to restore the bactericidal activity of sera from x-irradiated rabbits.
The Use of RDE to Improve the Sensitivity of the Hemagglutination-Inhibition Test for the Serologic Diagnosis of Influenza
Authors: Jordan William S. , Oseasohn Robert O.
Published: January 2023

To aid in the selection of a serologic procedure best suited for the measurement of changes in the levels of influenza antibodies in serum specimens collected from individuals at six month intervals, paired sera from 58 patients with influenza and other acute respiratory illnesses were tested by the complement-fixation and hemagglutination-inhibition techniques employing PR8, FM1, Lee and 1233 influenza virus antigens.

By using the complement-fixation test for reference, it was shown that destruction of heat stable (62°C) non-specific inhibitor by RDE increased the sensitivity and reliability of the hemagglutination-inhibition test in 22% of the cases. RDE did not alter serum inhibitor levels against 1233 virus. RDE affected a greater reduction of inhibitor active against Lee antigen than of inhibitor against PR8 or FM1 antigens.

With proper antigens, the hemagglutination-inhibition test on RDE treated sera is as sensitive as the complement-fixation test with virus antigen. It has been shown by others that use of soluble antigen increases the sensitivity of the complement-fixation test, but the antibody elevation measured is transient. It is believed that the hemagglutination-inhibition test using RDE is the method of choice for measuring changes in the level of influenza antibodies in serum specimens collected at wide intervals.
Cytopathogenic Agents Isolated from Patients during an Unusual Epidemic Exanthem
Authors: Neva Franklin A. , Enders John F. , Chang Yinette
Published: January 2023

A group of agents cytopathogenic for tissues of human origin was isolated from the feces of seven patients during an epidemic exanthem in the late summer of 1951. Isolation of the agents was effected in suspended cell cultures of kidney tissue and subsequent propagation in roller tube cultures of human embryonic skin-muscle, postnatal foreskin or myometrium. Evidence for the development of neutralizing antibodies against the agents was obtained in almost all of the patients whose blood specimens were tested. Cross neutralization tests indicated that the new agents are immunologically closely related. Further study is needed to establish with certainty the etiologic relationship suggested by the data now available between this group of agents and the disease with which they were associated.
Studies on the Interaction of the Large and Small Hemagglutinating Components of Newcastle Disease Virus with Red Cells
Authors: Granoff Allan , Henle Werner
Published: January 2023

Partially purified preparations of the L and S components of Newcastle disease virus were obtained from infected allantoic fluid and membrane suspensions, respectively, by differential centrifugation. The L component could be separated also from the infected tissues but S could be detected in allantoic fluid only in relatively low concentrations. The S component was found to be partially sedimentable by centrifugal forces far in excess of those needed for removal of L. Suspension of the L component revealed ID50/HA ratios of the order of 106. In contrast, S preparations gave ratios as low as 100.6 and generally below 102.

Whereas L was readily absorbed onto red cells in the cold, only relatively small amounts of S appeared to combine with these cells under the same conditions. No inhibitor of adsorption could be detected in S preparations. The data presented suggest that the S component either possesses greater eluting activity than L or that an elution-promoting factor is present in such preparations.

The L component readily causes hemolysis whereas S according to all indications lacks this property. When red cells were exposed to S and subsequently washed they resisted hemolysis by the L component. Heated S or control material had no such effect.

Only the L component showed the phenomenon of extension of titers in hemagglutinin assays upon repeated resuspension and settling of the red cells at 37°C. Only red cells previously exposed to L at 37°C until stabilized could be agglutinated by dilute NDV-immune serum or were capable of agglutinating normal red cells. These properties, according to Burnet, are closely linked with the hemolytic activity. The facts that S failed to reveal these reactions and was found to be non-hemolytic appear to be in agreement with this suggestion.

Under carefully graded conditions S precedes the L component in the receptor gradient.

Various problems concerning the mechanisms of interaction of these components with red cells have been discussed.