bluuebunny/crossref_metadata_2025 huggingface dataset:
The Fate in Rabbits of Intravenously Injected I131-Iodoovalbumin
Authors: Haurowitz Felix , Crampton Charles F.
Published: January 2023

The fate of the trichloracetic acid-precipitable radioactivity of I131-iodoovalbumin in intravenously injected rabbits was investigated on both the gross organ level and the subcellular level. The determinant groups of the iodoproteins appear to be stored in the tissues for an indefinite length of time. After their injection they are concentrated briefly in the microsomal fraction of the liver and spleen. This is followed by a long term concentration in the mitochondrial fraction.

The administered dosage did not seem to influence the pattern of intracellular distribution of radioactivity up to 24 hours following an injection. Previous intravenous injections of non-radioactive iodoovalbumin did not greatly alter the organ deposition or distribution among the liver fractions of a final labeled injection.

The experimental results are consistent with the concept that antibody formation is a cytoplasmic phenomenon occurring in the presence of the antigen. The antigen involved in antibody formation is most likely concentrated in the mitochondria.
Studies in Specific Hypersensitiveness
Authors: Spain W. C.
Published: January 2023

The typical vesicular lesion of Dermatitis venenata can be produced by means of an alcoholic or chloroform extract of the fresh leaves of Toxicodendron radicans, applied to the skin surface. In our hands, the typical vesicular lesion of Dermatitis venenata could not be produced by the intradermal injection of an active alcoholic extract. The lesion thus produced was not different from that caused by the intradermal injection of the solvent. With the patch test, differences can be demonstrated in the susceptibility of different individuals to poison ivy, and in the incubation period of the lesion. With the technic used, infants could not be shown to be susceptible.
Studies in Specific Hypersensitiveness
Authors: Coca Arthur F. , Deibert Olin , Menger Edward F.
Published: January 2023

Through inquiry it has been found that the American Indian is apparently much less frequently affected by the allergies than is the white race. An experimental study of the occurrence of serum disease in twenty-six volunteer full-blood American Indians indicates that the Indian race is much less susceptible to that condition than is the white race.

This similarity in the relative susceptibility of the two races to these two conditions suggests a similarity in the underlying mechanism of both of the conditions which, however, need not amount to a complete identity.
The Hemagglutination Test for Rheumatoid Arthritis
Authors: Heller George , Kolodny Maxwell H. , Lepow Irwin H. , Jacobson Abraham S. , Rivera Maria E. , Marks Grace H.
Published: January 2023

Modifications of 2 hemagglutination procedures—the SEA and FII tests—for the identification of the rheumatoid agglutinating factors are described. Fractions II, III, IV-1, IV-4 and V were prepared by existing ethanol fractionation procedures from sera of patients with rheumatoid and non-rheumatoid diseases. Only Fraction III prepared from sera of patients with active peripheral rheumatoid arthritis and psoriatic arthritis produced positive reactions with the SEA and FII tests. The rheumatoid factors were not demonstrated in the serum or its fractions from patients with other types of rheumatoid and non-rheumatoid diseases. The electrophoretic characteristics of Fraction III were not indicative of the presence of the rheumatoid agglutinating factors. The iso-antibodies and the rheumatoid factors present in Fraction III were shown by absorption procedures to be qualitatively distinct immunological reactants. By absorption and cross reaction procedures, we established that the reactants in the SEA and FII tests were heterogenetically related. Variations in the reactivity of rheumatoid sera as well as their derived Fraction III for the SEA and FII reagents were observed. Several aspects of the hemagglutination reactions are discussed.
Studies with Influenza Virus B of Recent Human Origin
Authors: Ledinko Nada , Perry Beverley
Published: January 2023

The biphasic course of adaptation to the mouse lung of a type B influenza virus of recent human origin is described. Inoculation of the virus resulted in the production of extensive pulmonary consolidation and multiplication of virus as determined by hemagglutinin and egg infectivity titrations of bronchial washings. Continued passage resulted in a gradual decrease in consolidation and a depression of multiplication resulting in no demonstrable hemagglutinin and a decrease in egg infectivity titer. A subsequent gradual rise in consolidation and an increase of hemagglutinin and egg infectious particles were found. During the early phases of adaptation, a “functionally deficient” form of virus was produced. A study of the character of the lesion-producing capacity of the unadapted virus revealed that (a) the extent of lung lesions obtained paralleled the dosage of virus inoculated, and (b) the extent of consolidation produced was found to correlate with the production of hemagglutinin units. Continued passage in the chick embryo resulted in a diminished ability of unadapted virus, upon introduction into the mouse lung, to multiply and to produce consolidation.
Fall in Rectal Temperature as an Indication of Anaphylactic Shock in the Mouse
Authors: Kind Leon S.
Published: January 2023

A fall in rectal temperature regularly accompanies anaphylactic shock produced by the intraperitoneal injection of horse serum into horse serum-sensitized mice. The dose of horse serum which lowered the temperature of sensitized mice did not cause a drop in the temperature of non-sensitized control animals. Much larger doses of horse serum also had little effect on the rectal temperature of non-sensitized mice. The advantages to be derived from the use of thermal measurements in anaphylaxis are discussed.
Differentiation and Purification of Influenza Viruses by Adsorption on Aluminum Phosphate
Authors: Miller Herbert K. , Schlesinger R. Walter
Published: January 2023

A study of the adsorption of five strains of influenza virus on aluminum phosphate has been presented. Each strain shows a characteristic adsorption pattern which can be used for rapid and efficient differentiation. This information has been applied to the separation of an artificial mixture of the PR8 and Lee strains.

The method was applied to the purification of large batches of Melbourne strain by the use of supported columns. Eleven purified samples of virus harvested 14 hours after inoculation of 10-3 diluted seed virus gave an average log (ID50/g.N) of 15.2 with a range of 15.0 to 15.3. Criteria for the degree of purity of these samples have been presented.

Within the limits of experimental error, the yield was quantitative. No significant inactivation of virus was encountered.
Quantitative Studies on the Bactericidal Actions of Serum and Complement
Authors: Muschel Louis H. , Treffers Henry P.
Published: January 2023

A rapid photometric assay method is presented for the titration of the bactericidal activity of antisera or of complement. Like the conventional plate count assay method it requires an initial reaction period, during which the organisms, antibody, and complement interact. In our method, the relative numbers of organisms surviving are then determined by their growth rate properties on subculture, the quantitation of the relative total growth being made with a photoelectric colorimeter. Linear plots are obtained (on normal-deviate or probit graph paper) between the percentage kill and the dosage (in logarithmic units). From this the 50% end point and the response slope may be determined. If the culture density is standardized, the standard deviation of the absolute titer is about 10%; without such control, only the titers relative to a reference serum may be determined with this precision. Several factors which influence the test are discussed.
Studies of the Retention and Properties of S35 Labeled Antigen in Livers of Immunized Rabbits
Authors: Garvey Justine S. , Campbell Dan H.
Published: January 2023

The rate of loss of S35 from livers of rabbits, which had received nine injections of tagged antigen, diminished with time and became fairly constant at four weeks after the last injection. The percentage of antigen retained at six weeks in the liver, as based upon total amount injected, was less for rabbits which received repeated injections than for those which received only a single injection. Antigen in the soluble fraction of liver was present in two forms as shown by electrophoresis, salt-precipitation and serological activity. Three days after the last of nine injections, both precipitating antigen and non-precipitating antigen (by specific inhibition) were present. Five to six weeks later only non-precipitating antigen was present.
Virus Yield Per Cell in Monkey Kidney Cultures Inoculated with Different Strains of Poliomyelitis Virus
Authors: Youngner J. S.
Published: January 2023

A technique has been devised to estimate virus yield per cell in cultures of trypsin-dispersed monkey kidney cells infected with different strains of the three immunologic types of poliomyelitis virus. Under the conditions employed, the range of variation in plaque-forming units produced per cell by 7 type 1 strains was from 132–612 (mean 256); for 6 type 2 strains from 68–270 (mean 151) and for 5 type 3 strains from 36–127 (mean 87).
The Incidence of Antigen J in Cattle and the Production of Anti-J by Isoimmunization
Authors: Elliott Robert A. , Ferguson L. C.
Published: January 2023

The study of the incidence of the J antigen in cattle demonstrated that 55.3% of the cattle tested possessed the antigen in the soluble form. In hemolytic tests for the cellular antigen, 34.5% of the animals reacted with one serum and 23.9% reacted with the other serum. Thirty-seven % of the J-positive animals were not detectable by the hemolytic test.

The naturally occurring antibody was detectable in the serum of 23.5% of the animals at the time they were tested. It was impossible to demonstrate either antigen or antibody in the serum of 21.2% of the animals. These animals are thought to be capable of producing antibody for J antigen.

Isoimmunization, with the J antigen in the form of whole blood, plasma-free red blood cells, and cell-free plasma, stimulated the production of antibodies specific for the J antigen.
The Effect of Cortisone on Isohemagglutinin Production in Mice
Authors: Kaliss Nathan , Hoecker Gustavo , Bryant Bradley F.
Published: January 2023

Isohemagglutinins were produced in C57 Black mice, in response to the injections of extracts of three different transplantable mouse tumors, each indigenous to a different inbred strain (other than the C57 Black). These hemagglutinins will cross-react with the red cells of mice of each of the three inbred strains to which the tumors are indigenous. It was found that: (a) cortisone inhibits antibody production when injected simultaneously with any of the three tumor extracts during primary immunization. The inhibition persists for up to three and one-half months when mice are reimmunized with one of the tumor extracts, or when a second one of the tumors is used for the succeeding immunization, though no cortisone is administered after the primary immunization. However, antibody is produced to the third tumor, no matter which tumor had been used for primary immunization; (b) mice, in which antibody production has been established by primary immunization (no cortisone administered), exhibit a marked secondary response though cortisone is administered during reimmunization.
A Soluble Antigen of Phase 1 Hemophilus Pertussis
Authors: Kuwajima Yoshio , Masui Masamiki , Asano Asao , Matsui Toshitaka
Published: January 2023

A formula for a fluid medium containing neither starch nor carbon was described and was used for the cultivation of phase 1 Hemophilus pertussis.
In Vivo Studies on Precipitin Production by the Rabbit Spleen
Authors: Stevens Kingsley M. , Riley Philip A.
Published: January 2023

Three-kilogram rabbits were injected intravenously, intrasplenically and intraportally with 4 or 40 mg of alum-precipitated bovine γ globulin (BGG). At both dosage levels the peak precipitin responses were as follows: intravenous >; intrasplenic = intraportal. Antibody responses of small groups given soluble BGG were intravenous = intraportal > intrasplenic.

In an attempt to determine any correlation between antigen concentration in an organ and serum antibody levels, the distribution of soluble and alum-precipitated I131 human serum albumin (HSA) was studied in certain organs of normal rabbits at 15 minutes and 24 hours after intravenous, intrasplenic and intraportal injections. No good correlation was found. An unexpected finding was that, when injected intravenously, eight times as much antigen was found in the lungs 15 minutes after alum-precipitated antigen as after soluble antigen.

Splenectomized rabbits produced about 40% as much antibody as controls following intravenous injection of alum-precipitated BGG.
The Influence of Immunization and Total Body X-Irradiation on Intracellular Digestion by Peritoneal Phagocytes
Authors: Donaldson David M. , Marcus Stanley , Gyi Ko Ko , Perkins Eugene H.
Published: January 2023

Total body x-irradiation suppresses intracellular digestion of chicken erythrocytes by the peritoneal phagocytes of mice and rabbits. Such digestive function was normal on the second and eighteenth postirradiation days but was depressed on the sixth through the fourteenth day following 350-r total body irradiation of mice. When the irradiation dose was increased to 450 r, digestion of chicken erythrocytes by mouse phagocytes did not return to normal until the twenty-sixth day. The inhibition of phagocyte digestion of Candida guilliermondi followed the same pattern as observed with chicken red blood cells. Immunization with chicken erythrocytes caused an increase in the digestion of these cells by the phagocytes from mice and rabbits. The immunization-induced increase in digestive capacity was reversed by irradiation procedures that did not appreciably alter serum antibody titers. In vitro tests carried out in the presence of serum from immunized and immunized-irradiated rabbits revealed that the beneficial effect of immunization and the detrimental effect of irradiation on phagocyte digestion were due to alterations in the phagocytic cell and not due to the humoral changes that follow irradiation or immunization.
The Development of the Phage-Inactivating Properties of Serum During the Course of Specific Immunization of an Animal: Reversible and Irreversible Inactivation
Authors: Jerne Niels K. , Avegno Perla
Published: January 2023

Sera obtained from early and late bleedings of the same animal during the course of immunization against bacteriophage T4 are different in character. Among the T4 particles inactivated by such sera two fractions can be distinguished, one of which can be reactivated on dilution, the other not. In late serum the former fraction is minute; inactivation is practically irreversible. In early serum a large fraction of the inactivated particles can be reactivated on dilution.

Reactivation is approximately a first order process. The rate of reactivation is decreased by lowering the temperature or the ionic strength of the medium.
The Presence in Normal Serum of Specific Antibody Against Bacteriophage T4 and Its Increase During the Earliest Stages of Immunization
Authors: Jerne Niels K.
Published: January 2023

The sera of normal animals contain minute amounts of a specific antibody A which can act on T4 bacteriophage. The relative concentrations of antibody A in different sera can be precisely measured. The concentration of antibody A in the blood of an animal may be increased by a factor 100 within 4 days after stimulating the animals with a single injection of T4 antigen. It is not increased on immunization with unrelated antigens. On immunization with T4 phage the production of antibody A precedes the production of T4-inactivating antibodies in time, and thus provides a means of investigating the early stages of the response of an animal to an antigen stimulus. Antibody A reveals its presence by permanently activating T4 particles of certain strains which are reversibly activated by tryptophane and other cofactors. The kinetics of activation suggest the following points concerning the activation mechanism. Structures at each of about five sites on a T4 particle oscillate independently between two states. A particle can become active when all sites are simultaneously in the positive state. Antibody A, tryptophane, and indole act only on individual positive sites, retarding or precipitating their relapse into the negative state.
The Antitoxin Response of Schick-Negative Rheumatic and Non-Rheumatic Subjects to Diphtheria Toxoid
Authors: Quinn Robert W. , Bridgforth Edwin B.
Published: January 2023

Nineteen Schick-negative children with rheumatic fever and 18 Schick-negative non-rheumatic children were given a booster dose of diphtheria toxoid subcutaneously. There were marked individual differences in antibody response but no significant differences between the group of rheumatics and the group of non-rheumatics. Diphtheria antitoxin precipitated in the toxin-antitoxin complex was much less than the amount actually present as measured in vivo in the rabbit. There appeared to be no definite evidence for the production of non-precipitating, skin-sensitizing antibodies by either rheumatics or non-rheumatics. The findings of this experiment furnish further evidence that Schick-negative individuals with rheumatic fever in either the active or inactive phase do not respond differently to diphtheria toxoid than do non-rheumatic individuals.
Effects of Trypsin and Certain Surface-Active Agents on Meningo-Pneumonitis Virus and on Normal Chorio-Allantoic Membrane Particulates
Authors: Crocker T. Timothy
Published: January 2023

Summary and Conclusions

Crude suspensions of meningo-pneumonitis virus from infective allantoic fluid (IAF) and particle suspensions from homogenates of normal chorio-allantoic membranes (NCAM) of chicken embryos were prepared by identical centrifugation and were adjusted to comparable turbidity. The NCAM suspension was considered to be a reasonable control for the IAF suspension because both reacted similarly on incubation with trypsin and morphologically similar particles appeared in both suspensions. Essentially all particles in NCAM and 30 to 50% of particles in IAF suspensions were destroyed by desoxycholate and digitonin under conditions which did not reduce viral infectivity. Two particle classes remained in IAF suspensions after detergent treatment: typical elementary bodies and large forms of 0.5 to 2.0 μ diameter. The large forms were altered tinctorially by detergent exposure which did not alter viral infectivity and some were reduced to empty membranous “ghosts.” Exposure to surface-active agents under conditions which lowered viral infectivity caused nearly the same tinctorial changes in elementary bodies as lesser exposure had produced in large forms, and “ghosts” of elementary bodies appeared. The similarity between elementary bodies and large forms, and the resistance of these structures to treatment which destroyed normal tissue particles, strengthens the morphologic identity of the large forms as viral components of the P-LV group and provides a means of purification of the virus.
Immunologic Studies on Persons Residing in a Plague Endemic Area
Authors: Payne Francis E. , Smadel Joseph E. , Courdurier Jean
Published: January 2023

Conclusion and Summary

The current work adds information on the character of the serologic response in persons recovered from pneumonic or bubonic plague and establishes that this response is modified by vaccination. Unvaccinated persons recovered from either form of the disease usually possess appreciable levels of antibody against capsular protein for months or years but rarely maintain significant amounts of antitoxin. In contrast, those who had been vaccinated prior to infection usually have appreciable amounts of both types of antibodies for months or years after recovery.

It was concluded on the basis of the limited experience of others and ourselves that a single inoculation of living attenuated P. pestis, strain EV, elicits demonstrable antibody and antitoxin in relatively few persons. The present study clearly demonstrates that after basic immunization with strain EV, subsequent injections of the vaccine over a period of years progressively enhance the production and maintenance of the antibodies by the individual and by the group.

The detection of antibodies against the capsular protein and toxin of P. pestis in sera of a few Malgache with no known history of plague or vaccination once again raises the possibility that unrecognized and possibly clinically inapparent infections with P. pestis do occur in persons residing in an area endemic for plague.

Purified murine toxin of P. pestis produces erythema and edema in the skin of normal persons but intradermally injected capsular protein is relatively non-toxic. In general, fewer vaccinated and unvaccinated Malgache reacted positively to toxin than did normal American volunteers. As little as 11 μg of intradermally injected capsular protein, unlike a similar amount of toxin, elicited an appreciable specific antibody response in the majority of previously vaccinated, but not unvaccinated, persons. Comparison was made between dermal reactivity to these 2 antigens and the concurrent level of circulating specific antibody; however, no clear-cut relationship between skin reactivity and circulating antibody was forthcoming.
The Tuberculin Reaction
Authors: May Karl J. , Weiser Russell S.
Published: January 2023

Observations on a large number of explants of corneal epithelium from tuberculin-sensitive guinea pigs grown in the presence of OT and PPD indicate that tuberculoprotein does not exert a cytotoxic action on such cells.
A Comparative Study of Type 2 Poliomyelitis Viruses
Authors: Wenner Herbert A. , Kamitsuka Paul , Lenahan Margaret , Melnick Joseph L. , Melnick Joseph L.
Published: January 2023

An antigenic analysis of 18 type 2 polio viruses has been made by means of cross-neutralization tests in tissue culture. Differing antigenic components entered into the constitution of the various strains making it possible to classify them into three major categories, namely, strains identical or closely related to the prototype Lansing virus, strains distinctly different from the Lansing virus, and intermediate strains.

Differences in antigenic constitution of the type 2 polio viruses studied were observed in reciprocal CF tests using 1) the strains as viral antigens and studying their reaction with reference heterotypic sera, and 2) type 2 antisera and reference viral antigens of the three polio virus types and studying their reaction with antisera prepared against each of the type 2 strains under study. On the basis of these tests at least four of 15 type 2 polio viruses studied contained type 1 components in the composite antigenic structure.
Studies of the Immunochemistry of Leptospires
Authors: Rothstein Nathaniel , Hiatt C. W.
Published: January 2023

Extraction of leptospiral cells with 70% ethanol yielded a product which could be subdivided into two portions on the basis of solubility in distilled water. The soluble portion contained two antigenic components as evidenced by its ability to invoke both genus-specific precipitins and type-specific agglutinins in the rabbit. The agglutinins could be removed from antiserum by absorption with homologous organisms.

On the basis of these observations, it was postulated that leptospires contain two major antigenic components: a P antigen, which is a peripheral, type-specific principle, and an S antigen, which is a somatic, genus-specific principle. The S antigen appears to be a lipopolysaccharide; the chemical nature of the P antigen remains undefined.
Characteristics of the New Respiratory Viruses (Adenoviruses)
Authors: Ginsberg Harold S.
Published: January 2023

Neutralization titrations carried out with types 1–4 APC-RI viruses and type-specific rabbit sera, as well as human convalescent sera, indicated that preliminary incubation of virus-serum mixtures at 22° or 37°C was necessary to obtain maximum titers. Prolongation of the incubation period beyond 30 min did not increase the neutralization titer appreciably; with human convalescent sera, neutralization titers were similar whether a mixture of serum and either type 3 or 4 virus was incubated 30 min at 4°C or 120 min at 37°C.

Investigation of the quantitative aspects of the neutralization reaction with the new respiratory viruses and type-specific immune sera indicates that the reaction between the two components, expressed as logarithms to the base 10, describes a linear relationship. The ratio between the two variables, the logarithm of the quantity of virus neutralized and the logarithm of the serum dilution end point, was 1.0 for types 3 and 4 viruses and 2.0 for types 1 and 2 viruses. The species of animal from which serum was obtained for the neutralization titrations did not influence the slope of the neutralization line.
Precipitin Production in Chickens
Authors: Gengozian Nazareth , Wolfe Harold R.
Published: January 2023

Aging of chicken antisera at 4°C or at -20°C resulted in: (a) an increase in interfacial titers with tests performed in 1.8% NaCl. (b) a decrease in nitrogen precipitation when the quantitative tests were performed in 8% NaCl. (c) an increase in nitrogen precipitation with most antisera when the quantitative tests were performed in 1% NaCl. Inactivation of chicken complement by versene is to be preferred to heat (56°C, ½ hour) since the latter may contribute to the co-precipitation of nonspecific nitrogen when the quantitative test is performed in 8% NaCl. Treatment with versene decreased the nitrogen precipitation in the antigen excess region of the precipitin curve. This was quite evident in 1% NaCl. Some explanations for the points noted above were given.
Cross Reactions of Polyglucoses in Antipneumococcal Sera
Authors: Heidelberger Michael , Jahrmärker Hans , Björklund Bertll , Adams John
Published: January 2023

A synthetic polyglucose fraction is shown to precipitate more antibody nitrogen from Types II, IX, XII, XX, and XXII antipneumococcal horse sera than do various glycogens, amylopectins, and other natural polyglucoses. Quantitative data are given. Various features of these cross reactions and the compositions of certain of the precipitates are discussed. Use is made of the action of amylase on glycogen-antibody precipitates for the partial purification and concentration of cross-reactive antibody. Preliminary results are given with an analytical method which appears to provide a new criterion of homogeneity for carbohydrates composed of a single sugar or polysaccharides not fractionated by a single precipitation with an antiserum.
The Purification of Poliomyelitis Virus as Studied by Complement Fixation
Authors: Mayer Manfred M. , Rapp Herbert J. , Roizman Bernard , Klein S. Wayne , Cowan Keith M. , Lukens David , Schwerdt Carlton E. , Schaffer Frederick L. , Charney Jesse
Published: January 2023

Summary and Conclusions

Complement fixation (CF) assays for poliomyelitis virus and for monkey kidney antigens have been found useful in guiding and controlling the processes of concentration and fractionation required for the purification of poliomyelitis virus. In conjunction with infectivity measurements, as well as nitrogen analyses, CF titers furnish information on yield and purity. Three variations of the basic purification procedure have been studied with respect to yield and purity gain. Usually, the yield of purified virus was equal to or better than 50%, with purity gains up to about 1000-fold relative to the starting material. The infected tissue culture fluids (ITCF) used as starting material were found to contain about 0.01 to 0.2 μg of virus nitrogen/ml. ITCF from minced tissue cultures contained about 20 μg of total non-dialyzable N per ml, while ITCF from cultures of the trypsinized type contained only about 3–5 μg of total non-dialyzable N. Concomitantly, the former type of ITCF showed monkey kidney antigen titers by CF about 40 times greater than those of the latter type. Tentative estimates indicate that the most highly purified fractions were composed primarily of viral substance. Those which were derived from ITCF of the minced tissue type still contained appreciable amounts of monkey kidney substance, perhaps 25%. On the other hand, purified products from ITCF of the trypsinized type were free of detectable monkey kidney antigens, but the presence of non-antigenic contaminants could not be excluded. However, only a small proportion, somewhat less than 0.1%, of the actual mass was infectious virus, as detected on monkey kidney cultures. The remainder, presumably represents non-infectious virus, or viral products, which are immunologically reactive but which do not form plaques on tissue cultures. Fractionation of purified products by ultracentrifugation in a sucrose density gradient (SDG) led to a separation of fast sedimenting infectious units from slower non-infectious components. Both were reactive in CF tests with polio antisera. It is shown that infectivity titers should not be used as a measure of viral substance, but, instead, CF titers should be employed.
Reactivity of Influenza A and B Viruses Propagated in Cultures of Human Embryo Tissues and in the Chick Embryo
Authors: Simpson Georgie I. , Mogabgab William J. , Wilson L. D.
Published: January 2023

Influenza A (1953) and B (1954) isolated and propagated in human embryo tissue cultures differed from the same viruses passaged only in the chick embryo in regards to certain hemagglutination characteristics and other reactions with receptors. Thus, fowl erythrocytes were agglutinated at 4°C but not at 25°C by the TC line of influenza A and at either temperature by the E line. The former even when inactivated did not agglutinate sheep red blood cells, while the latter agglutinated these cells at 4°C but not at 25°C. Temperature dependence of the reaction with sheep erythrocytes was also demonstrated with the TC line of influenza B, and titers were lower than those with red blood cells from other species. The E line of this virus, in contrast, agglutinated sheep cells at either temperature and at relatively higher titers.

Disagglutination of the virus-erythrocyte patterns occurred at a more rapid rate with the TC lines of influenza A and B than with the E line. This was observed at 5°, 25° and 37°C, with human, fowl, sheep and monkey erythrocytes, and with adsorbed-eluted virus as well as that contained in tissue culture or allantoic fluids. Patterns with human and fowl erythrocytes were maintained when inactivated virus was used except for the TC line of influenza A with fowl red blood cells.

Elution rates of both TC viruses from human and fowl erythrocytes were more rapid than those of the E lines at 25 or 37°C. The TC line of influenza A was adsorbed poorly by fowl erythrocytes and not at all by sheep red blood cells. Both lines of influenza B were adsorbed more rapidly by fowl than human erythrocytes Degree of adsorption was correlated with hemagglutination behavior. The virus-erythrocyte combinations that agglutinated at 25°C showed more virus adsorption at 15–24°C, while those that required 4°C were adsorbed more rapidly at the same temperature. Amount of inactivated virus adsorbed increased progressively with temperatures between 5 and 37°C.

More human urinary mucoprotein was required to inhibit hemagglutination by the TC lines of both viruses. Also, higher dilutions of normal rabbit serum inhibited the TC line of influenza A than the E line; slight differences in the opposite direction were found with influenza B. Differences between the virus lines in enzymatic activity as determined by receptor destruction were not demonstrable with human urinary mucoprotein, intact erythrocytes or their extracts.

Both lines of influenza A behaved similarly in adapting to the mouse lung after serial passages. The E line, however, lost its adaptation to the allantoic sac and ability to agglutinate fowl cells at 25°C after mouse passages. The E line of influenza B adapted to the mouse lung after approximately the same number of passages as influenza A. The TC line, on the other hand, did not adapt even with 23 passages.
Demonstration of Antigenic Relationship between Mumps Virus and Hemagglutinating Virus of Japan
Authors: DeMeio Joseph L. , Walker Duard L.
Published: January 2023

In sera from 22 of 24 cases of clinical mumps infection in young adults a heat stable factor reactive with the Hemagglutinating Virus of Japan (HVJ) increased in titer during the course of the illness. This factor was not affected by RDE and was measurable by the hemagglutination inhibition, complement fixation, and neutralization techniques. A similar response was not detectable in rabbits or mice following injection of mumps virus.

Sera from 60 individuals were tested for activity against both HVJ and mumps virus. Twenty-eight were found to inhibit HVJ and detectable antibody against mumps virus was found in 22 of these, suggesting that much of the antibody against HVJ found in sera of persons in the United States may be the result of mumps infection rather than actual infection with HVJ.
A Study of Experimental Encephalomyelitis Employing Mammalian and Nonmammalian Nervous Tissues
Authors: Paterson Philip Y.
Published: January 2023

Three species of nonmammalian nervous tissue (frog, snake and turtle) failed to elicit experimental encephalomyelitis in the Hartley guinea pig, in contrast to the known and demonstrable paralytogenic activity of rabbit brain for this host.

Both mammalian (rabbit) and nonmammalian (frog, snake and turtle) nervous tissues stimulated the production of CF antibrain antibodies in rabbits. Such antibodies cross reacted with and could be absorbed by either mammalian or nonmammalian brain. Thus, it is concluded that the CF antibrain antibodies are stimulated by at least one antigenic component common to both mammalian and nonmammalian nervous tissue.

Both mammalian and nonmammalian brain tissues elicited CF antibodies; only mammalian brain produced paralysis. Thus, these CF antibrain antibodies appear to be directed against an antigen(s) of a nonparalytic character and would appear to play no direct role in initiating encephalopathy.
Effective Passive Immunization of Mice Twelve Days after Intracerebral Inoculation of Type 2 Poliovirus
Authors: Evans C. A. , Chambers Velma C. , Hotta Susumu , Wood E. M.
Published: January 2023

Summary and Conclusions

In 3 experiments more than 900 mice were inoculated intracranially with approximately 1 to 8 LD50 of type 2 poliovirus of the Y-SK strain. Treatment on the 12th day with type specific antiviral antiserum prepared in monkeys caused a clear reduction in subsequent mortality. This was most strikingly shown in the experiment in which serum was derived from monkeys immunized with virus grown in monkey kidney tissue culture.

It is concluded that in many animals specific antiserum to type 2 poliovirus terminated infection that had existed 12 days in the central nervous system. It is suggested that antibody was effective in the quiescent phase of the infection which has been shown to occupy most of the incubation period in mice undergoing prolonged incubation periods.
Repository Immunization in Pollen Allergy
Authors: Loveless Mary Hewitt
Published: January 2023

In a longitudinal study extending over 17 years and associated with statistical analysis, 117 ragweed-allergic individuals have been given 749 annual courses which alternated between conventional, multi-visit injections and single-visit repositories of the Freund type. In comparing the effectiveness of these two methods of immunization, three criteria were applied: the customary clinical estimate obtained from the patient at the end of each pollinating season, his daily diary of hay fever hours, and a controlled variety of conjunctival test which gaged the acquisition of blocking antibody by the tissues. Whereas these served as yardsticks of clinical and immunologic effectiveness, the incidence of untoward reactions afforded the clue to the relative safety of the new and old procedures. The two procedures were found to be comparable in effect by all the criteria except that based on the conjunctival test. Here, the older method proved to be more effective by an amount that carried statistical—but not, however, practical—significance. The repository technique offers, therefore, a great saving in time without decreasing the practical advantages of therapy or increasing the risk of overdose reactions. It is possible that our schedules of dosage, which have depended on conjunctival classification of each patient, can be utilized by allergists who employ only the endermal or scratch methods of classification. A sizable minority of our ragweed-allergic group appeared to respond as well to placebo repositories as to active emulsions, according to their clinical reports and recorded hay fever hours. At the same time, no acquisition of blocking antibody was indicated by eye-test. Obviously, such placebo-responsive subjects should be excluded from experiments which compare the clinical efficacy of two therapeutic procedures. These patients stood in contrast with other individuals whose clinical reports promptly reflected any change from specific to placebo management. Such subjects should be responsible for the ultimate clinical opinion on repository therapy. No abscesses, cysts, or malignant growths have resulted from 1200 repositories used during the past 9 years. When either isopropyl myristate or corn oil was substituted for petrolatum in the repository, the number of overdose reactions was increased owing to a more rapid release of antigen. Clinical results were somewhat inferior with the substitutes. However, fewer nodules persisted beyond the season of pollination. This minor cosmetic problem surrounding the standard emulsion can probably be met by reducing the volume of mineral oil in repositories.
Studies on Mumps Virus
Authors: Tokuda Masao
Published: January 2023

Recovery of mumps virus and the appearance of antibodies were studied in guinea pigs after intracerebral, intratesticular or intracutaneous inoculation of diluted amniotic fluid infected with the Fujimura strain. Observations also were made after inoculation of the virus into the anterior chamber of the eyes. Mumps virus was recovered from the testicles for 3 days after intratesticular inoculation, from the brains for 4 days after intracerebral inoculation and from the fluid of anterior chamber of eyes for 7 days. In no case was virus recovered from the blood of the guinea pigs. With one exception, virus was not isolated from guinea pigs organs on the 2nd or later passages.

Complement-fixing, neutralizing and hemagglutination-inhibiting antibodies were demonstrable after inoculation by all routes. The highest titers were obtained after two intracerebral inoculations at 1-wk intervals. The intracerebral immunization of guinea pigs, therefore, appears to be the best and simplest method for the preparation of hyperimmune serum for complement-fixation tests. With complement-fixation test not only V-antibodies but also S-antibodies were detected in the sera of the guinea pigs after intracerebral inoculation with mumps virus.
Biologic and Serologic Characteristics of Echo Viruses from West Virginia
Authors: Ormsbee Richard A. , Melnick Joseph L.
Published: January 2023

The biologic and serologic characteristics of 30 echo viruses from Charleston, West Virginia, have been described. This group has been characterized as human enteric viruses which are not related to poliovirus, Coxsackie, herpes or adenovirus groups, which are not pathogenic for monkeys or newborn mice, but which produce cytopathic effects in tissue cultures of rhesus monkey kidney cells.

Twenty of the 30 were typable as echo types 3, 6, 7, 8, 9, 11, 14, or a new type no. 15. A number of the remaining untypable viruses show cross neutralization reactions in one direction only, indicating the possibility of mixtures of viruses, antigenic deficiencies, or variations within a single type as already known to exist in the echo-6 virus group.

The growth characteristics in monkey kidney, HeLa, and Maben cell tissue cultures have been described, and some strains have been shown to differ markedly in their ability to grow in these 3 cell types.

Neutralization of these echo viruses by donor sera has been correlated with some of their growth characteristics in tissue culture. Those echo viruses which produced cytopathic effects rapidly and produced high virus titers in monkey kidney cell cultures were strongly neutralized. Those which produced cytopathic changes slowly and yielded only low virus titers were only weakly neutralized by sera from their human donors, as measured in tube cultures by the inhibition of the cytopathic response.
Phagocytosis of Influenza Virus
Authors: Boand Arthur V. , Kempf J. E. , Hanson Robert J.
Published: January 2023

From data obtained using the fluorescent antibody technique of Coons and Kaplan it appeared that the influenza virus could be phagocytosed by human and rabbit leucocytes in vitro. It is believed that the virus was first adsorbed to the leucocyte following which penetration into the cell occurred. The reaction of phagocytosis was markedly enhanced by the presence of immune serum and by leucocytes from immune animals.
Heterogeneity and Average Combining Constants of Antibodies from Individual Rabbits
Authors: Nisonoff Alfred , Pressman David
Published: January 2023

Specifically purified anti-p-azobenzoate antibody from individual rabbits exhibits a large degree of heterogeneity with respect to free energy of combination with p-iodobenzoate, as measured by equilibrium dialysis. Antibody prepared from a pool of 5 sera was intermediate in heterogeneity among preparations from the individual sera comprising the pool. Quantitative indexes of heterogeneity and average equilibrium constants were obtained by application of the equations of Sips to the experimental data.

Average free energies of combination with hapten of purified antibody from the individual sera, a pool of these sera, and 3 other serum pools varied over a narrow range, indicating only small differences in the effectiveness of precipitating antibodies produced in the different rabbits. The results are discussed in terms of the mechanism of antibody formation.

A method for specifically purifying antihapten antibody in good yield is described. The procedure was shown to have no appreciable effect on the average combining constant or index of heterogeneity.
Preparation of Serologically Homogeneous Plague Murine Toxin and Its Reactions with Physical, Chemical and Enzymatic Agents
Authors: Ajl Samuel J. , Rust James , Hunter Donald , Woebke Jeanette , Bent Donald F.
Published: January 2023

By the use of the continuous-flow hangingcurtain electrophoresis apparatus developed by Karler, it has been possible to purify the murine toxin of Pasteurella pestis to such an extent that the final preparation exhibited only 1 band in the very sensitive gel precipitation techniques of Oudin and Ouchterlony. The final product had an intraperitoneal LD50 of 0.7μg for 16 to 20-g mice, and an intravenous LD50 of 0.2μg. Experiments are described which suggest that even this relatively pure toxin molecule may still contain portions which are not necessary for toxicity.
Purification of the Toxin of Pasteurella Pestis by Continuous-Flow Paper Electrophoresis
Authors: Spivack Martin L. , Karler Arthur
Published: January 2023

Continuous flow electrochromatography was an effective method for seperating the toxin of Pasteurella pestis from crude extracts. Large amounts of material were processed and a fine degree of fractionation achieved with no evidence of toxin loss. The number of antigens was reduced from 8 to 10 in the crude extract to 3 in the final product. The intravenous LD50 of the purified toxin in the mouse was 0.1 to 0.3 μg as compared to an LD50 of 5 to 15 μg for the crude extract. Toxin from the attenuated strain E.V. 76 behaved similarly in every way tested to the toxin isolated from the highly virulent strain 195/P.

The immunogenic properties of purified toxin from virulent and attenuated strains of P. pestis are under investigation.
An Intracellular Mortality-Enhancing Material from Malleomyces Pseudomallei
Authors: Lusby Monica , Levine H. B.
Published: January 2023

The injection of intracellular material obtained from either a virulent or a relatively avirulent culture of Malleomyces pseudomallei into mice caused marked enhancement of the lethal outcome of concurrent infection with this species. Mortality enhancement was demonstrated employing a number of strains of varying virulence for the mouse but not with 2 avirulent cultures. While enhancement of lethality was similarly demonstrated in infection with Pasteurella pestis, comparably derived material from the latter genus was without significant effect in melioidotic or plague infections. Administration of the intracellular material at 4 to 12 days prior to infection, rather than concurrently with the infecting dose, rendered the mice more resistant to the lethal effects of infection with M. pseudomallei.

The active enhancing component was purifed 19-fold and was shown to be a nondialyzable, heat stable, chloroform-resistant, ammonium sulfate-precipitable material free of detectable nucleic acids. Less than 60 μg/mouse of partially purified material elicited an enhanced mortality response. This and higher concentrations were nontoxic.
Elimination of Nonspecific Components from Viral Antigens by Fluorocarbon
Authors: Hamparian Vincent V. , Muller Ferdinand , Hummeler Klaus
Published: January 2023

Several viral complement fixing antigens derived from various host systems were treated with fluorocarbon. It was possible to remove undesirable reactivities such as anticomplementary activity and host component antigens from these preparations.

The specific complement fixing antigens demonstrated differences in their susceptibilities to the fluorocarbon treatment. Those of the Coxsackie and poliomyelitis groups tolerated successive treatments without loss in titers. Others, i.e., mumps and influenza virus (V) and soluble (S) antigens, were precipitated after 2 treatments.
In Vivo Purification of Isp131 Labeled Localizing Antirat Lymphosarcoma Antibody
Authors: Bale William F. , Spar Irving L. , Goodland Ruth L.
Published: January 2023

Summary and Conclusions

Antibody preparations were separated from the sera of rabbits immunized with a homogenate of rat Murphy lymphosarcoma plus Freund adjuvant. When labeled with I131 and injected intravenously into rats bearing this tumor, they showed substantial tumor localization. One day after intravenous injection the portion of the injected I131 found in the tumors of 20 rats averaged 6.8% of the injected dose in an amount of tumor equal to 1% of the animals' weight. This I131 concentration in tumor was more than twice the blood concentration at time of sacrifice and several times the concentration found in any other perfused organ or tissue. The tumor localizing substance behaved like γ-globulin with starch electrophoresis. Control studies with labeled normal γ-globulins indicated that most of the accumulation of I131 in tumor was specific and due to antibody to the Murphy tumor.

The antibody purification procedure involved a step in which a labeled crude antibody preparation was injected into tumor bearing animals, the animals sacrificed a day later, and the I131 labeled antibody attached to the washed homogenate of these tumors eluted into solution with 32% urea in pH 8 borate buffer.

Preparations made by completely in vitro methods gave less specific tumor localization.