bluuebunny/crossref_metadata_2025 huggingface dataset:
Phagocytosis of Microorganisms by Hela Cells
Authors: Shepard Charles C.
Published: January 2023

The activity of different species of animal sera in controlling the species of microorganism taken up by HeLa cells may be divided into two types on the basis of stability to heat, absorbability by Zymosan at 17°C, comparative activity of bovine fetal serum, and the species of microorganism acted upon. Activity that is promoted by bovine fetal serum is also promoted by some lots of horse serum and concerns mycobacteria, staphylococci and group A streptococci. The activity is duplicated by a combination of purified preparations of bovine fetuin and human albumin. Activities that are not promoted by bovine fetal serum are in most cases absorbable by Zymosan or heat labile. Included in this type is the action of dog serum toward Pasteurella tularensis, and guinea pig serum toward Brucella and Histoplasma capsulatum. A mixture of fresh and inactivated chicken serum promoted uptake of all the microorganisms. Following absorption with Zymosan, the activity was limited to the species in the first group, namely, mycobacteria, staphylococci, and group A streptococci. The absorption to Zymosan of the activity of dog serum for P. tularensis had requirements for temperature, ionic strength, and Mg++ that resemble closely those described for the reaction between properdin and Zymosan. Treatment of dog serum by methods designed to destroy C′1, C′2, and C′4 caused loss of its phagocytosis-promoting activity. The chicken serum activity for P. tularensis and the guinea pig serum activity for Br. suis had similar but somewhat different properties. Absorption of the guinea pig serum with Zymosan did not remove its activity for H. capsulatum, although it did remove that for Br. suis. Rendering the HeLa cell line free of PPLO did not change its behavior in phagocytosing bacteria.
Studies of Arthritis and Other Lesions Induced in Rats by Injection of Mycobacterial Adjuvant
Authors: Waksman Byron H. , Pearson Carl M. , Sharp John T.
Published: January 2023

A disseminated inflammatory disease affecting the joints, skin, eye and mucous membranes was produced in rats following injection with killed tubercle bacilli in oil. Intradermal inoculation and footpad inoculation in particular were more effective than other routes in producing this process. Litters of rats differed markedly in susceptibility. Animals less than 5 weeks of age appeared completely insusceptible. Rats with disease showed strong skin reactivity of the delayed type to tuberculin. Injection of tuberculin parenterally produced a transient flare-up of the disease process in the joints. Injection of tubercle bacilli in oil into diseased animals produced a very intense local reaction and, if given during the subsiding phase of the disease process, an accelerated reappearance of disease (anamnestic response). Disease production was largely suppressed by whole body irradiation (600 r). Single or repeated subcutaneous injections of tubercle bacilli or tubercle bacillus fractions, begun early in life, or a single footpad injection of bacilli in oil in the first 3 weeks of life, markedly inhibited later ability to develop the disease but did not prevent later susceptibility to allergic encephalomyelitis. Passive transfer of sensitized lymph node cells to normal, irradiated, or tolerant recipients permitted the induction of inflammatory responses to tuberculin in the ankle joints and ears. Local trauma or other nonspecific inflammation (turpentine injection) induced localization of the disease process in the affected areas.

The conclusion is drawn that the disease process is a delayed hypersensitive response to a disseminated antigen probably derived from the injected tubercle bacilli.
The Influence of Antimicrobial Agents on Total Populations of Staphylococci in Animal Tissues
Authors: McCune Robert , Dineen Peter , Batten John C.
Published: January 2023

The course of experimental infection with two strains of Staphylococcus aureus during antimicrobial therapy was studied in the mouse by the microbial enumeration technique. In agreement with previous observers, it was noted that both strains of staphylococci had the capacity to induce progressive disease in the kidneys whereas they were rather rapidly reduced in census in the spleen. With one of the strains, the lungs occupied an intermediate position, and a population increase occurred in this organ whereas with the other strain, the census drop in the lungs was comparable to that in the spleen of the same animal. This distinctive pattern of behavior in the three organs was not accompanied by impressive differences in the drug susceptibilities of the population situated in the three different organs when therapy was started at the time of infection. An apparent drug antagonism was observed when penicillin was administered with other antistaphylococcal drugs in the treatment of infections induced with the penicillin-resistant Giorgio strain. When treatment was delayed until renal lesions were established, there was a decrease in the effectiveness of streptomycin and novobiocin in reducing the renal staphylocococcal populations, whereas this delay did not curb the effectiveness of penicillin, oxytetracycline or erythromycin. With all five drugs employed and with both strains of S. aureus, microbial persistence was observed throughout the 28-day period. In no instance was the infection rendered truly latent with uniformity, i.e., among all the animals in a particular experimental group. There were indications that the distinctive pattern which staphylococci displayed with respect to drug-susceptibility in vivo obtained only during the first 2 weeks of the observation period. From this point on, with the exception of the observations made in the kidneys of the delayed streptomycin- and novobiocin-treated animals, in a total 4-week experimental period, all of the microbial populations tended to fall in a similar fashion. This suggests the operation of host factors in the latter period of the experimental situation. Attempts to evoke the dormant infection, to trace the course of the persisting organisms, and to evaluate the immunogenic characteristics of the persisting organisms are in progress.
Behavior of Intravenously Administered I131 Diphtheria Toxoid in the Guinea Pig
Authors: Masouredis S. P.
Published: January 2023

The distribution of I131 was studied in nonimmune guinea pigs following intravenous administration of trace labeled I131 diphtheria toxoid. The loss of I131 from the plasma could be attributed to three exponential components. The major fraction (85–90%) was removed at a rate of 69% per hr (T-½ = 1.0 hr) and the remaining 10–15% at two rates, one with a half-time of 5.5 hr and the other with a 37-hr half-time. The excretory loss of I131 from the guinea pigs occurred with two exponential rates, about 70% was excreted with a half-time of 9 hr and the remaining 30% with a half-time of about 100 hr. There was marked localization of I131 in the liver, spleen and kidney between 2 and 14 hr after administration of the toxoid, as determined by tissue to plasma ratios and I131 recovery calculations. Both toxin and toxoid are indistinguishable from each other when the concentration time course of I131 in the plasma and excreta are studied. The tissue distribution, however, differs significantly. I131 diphtheria toxin appears to be widely and diffusely distributed throughout all the tissues whereas I131 diphtheria toxoid appears to localize in the reticuloendothelial system (liver and spleen).
Studies on Actively Acquired Resistance to Experimental Cryptococcosis in Mice
Authors: Abrahams Irving , Gilleran Thomas G.
Published: January 2023

Effective resistance to lethal challenge (25 to 100 LD50) with Cryptococcus neoformans has been induced in mice by vaccination with suspensions of formalin-killed cells. A systematic study was made of factors influencing immunization and challenge such as the amount and route of antigen used, the degree of encapsulation of the killed cells, time of challenge and the number of organisms contained in the infecting dose. The importance of the amount of vaccine used was emphasized by the finding of a relatively narrow range between a quantity that evoked effective resistance and a larger quantity that caused a marked reduction in protection. Comparison of vaccines consisting either of small or of large encapsulated cells indicated that large capsule size was associated with decreased protective activity. This finding was observed in tests challenged either with homologous or heterologous cultures.

Confirmatory evidence of the effectiveness of immunization was obtained from cultural and histologic examinations of tissues from animals killed at intervals after challenge. Multiplication of cryptococci was largely inhibited in the livers and spleens of vaccinated mice whereas logarithmic rates of growth were observed in the corresponding organs of the controls. The brain examinations showed consistently lower counts of fungus cells in the treated group but the magnitude of the difference, in comparison with the controls, was considerably less than in the other organs that were studied.

The implications of some of these findings in relation to the altered course of the infection in vaccinated mice have been discussed.
Competition of Antigens
Authors: Abramoff Peter
Published: January 2023

The antibody responses of chickens simultaneously injected with 40 mg/kg body weight of bovine serum albumin (BSA) and human γ-globulin (HGG) in animals presensitized with either BSA or HGG are described.

Following simultaneous inoculation of BSA and HGG in animals previously sensitized with BSA, the responses to both of these antigens were significantly reduced, when statistically compared with their respective controls. Animals simultaneously injected with BSA and HGG following presensitization with HGG showed no significant reductions in antibody response to either antigen when compared with their respective controls. The significance of these results is discussed and a possible mechanism for the competition of antigens postulated.
Antibody Synthesis in Relation to Levels of Humoral and Cell-Fixed Antibodies in Rabbits
Authors: Sorkin Ernst , Rhodes Joan M. , Boyden Stephen V.
Published: January 2023

The rate of antibody synthesis was measured in vitro in fragments of spleens taken from rabbits killed at different times following an intravenous injection of human serum albumin (HSA), using the method based on the incorporation of C14-amino acids.

The values for synthesis were compared with the levels of “cell-fixed” antibodies, as expressed by uptake in vitro of I131-HSA, and also with the levels of precipitating antibodies in the sera, and with the capacity of the sera to confer on normal cells the ability to adsorb antigen (“cytophilic” antibody).

The investigation was carried out using rabbits which had received a single dose of antigen, rabbits which had received two injections, and hyperimmunized rabbits which had received a booster injection of antigen.

Antibody synthesis occurred in spleens taken 7–10 days after the first injection of antigen, or 3–5 days after a second or booster injection. The quantitative determination of “cell-fixed” antibody gave significant values only in the case of hyperimmune animals which had received a booster injection of antigen. Maximum adsorption of I131-HSA occurred in cells of spleens taken 3–6 days after the booster injection. Low precipitin titers were found in sera taken from animals 10 days or later, after a single injection of antigen, whereas sera of animals killed 3 days or later after a booster injection showed high precipitin titers. Significant levels of “cytophilic” antibody were found only in sera of rabbits killed 3 days or later after a booster injection.
Lysozyme Content of Alveolar and Peritoneal Macrophages from the Rabbit
Authors: Myrvik Quentin N. , Leake Eva Soto , Fariss Bruce
Published: January 2023

Normal rabbit alveolar macrophages have been analyzed for lysozyme content and they have been found to contain between 2000 and 4000 μg/ml of packed cells. A comparative study of the lysozyme content of oil induced peritoneal macrophages has revealed that peritoneal macrophages possess low levels of lysozyme. The possible role of alveolar macrophages as scavenger cells in the lung is discussed. It is postulated that macrophages may differ in their physiological and functional ability depending on their origin.
Isologous and Homologous Lymphoid Transplants
Authors: Bauer Joseph A. , Stone Sanford H. , McCleskey Robert I. , Goode Julius H.
Published: January 2023

The immunologic function of lymph node cell transplants between guinea pigs of a highly inbred, histocompatible strain (isologous transfer between Strain 13 guinea pigs) was compared to the function of transplants to incompatible recipients of another strain (homologous transfer: Strain 13 to Hartley guinea pigs). Lymph node cell suspensions were prepared during the second week after immunization of donors with complete Freund's adjuvant. The functional persistence of intraperitoneally injected donor cells was assessed by the degree of delayed cutaneous hypersensitivity of cell recipients to purified protein derivative (PPD). The transfer of immune cells in quantities inadequate to confer significant cutaneous hypersensitivity during the first posttransfer week, resulted in a high degree of tuberculin sensitivity in isologous recipients during the second and third weeks. In contrast, homologous recipients manifested no significant cutaneous reactivity during the 4-week period following identical cell transfers. The data are compatible with the interpretation that isologous recipients manifest adoptive immunity (passive immunity) which depends on the continued function and proliferation of surviving immune cells from compatible donors. The observation that the cells of one donor can confer a degree of cutaneous hypersensitivity as high as that seen in actively immunized (Strain 13) guinea pigs, may be related to graft-host compatibility as well as to the use of donors during the phase of rapidly ascending immunization and hyperplastic proliferation of lymph node cells. In isologous recipients, the degree of cutaneous reactivity in terms of the surface area (r2) of skin reactions was proportional to the number of viable cells transferred. This relationship was not observed in homologous recipients. Freeze-killed and sonically disrupted lymph node cells were either ineffective or minimally effective in conferring cutaneous tuberculin sensitivity. Spleen cells were found similarly ineffective in transferring tuberculin sensitivity. Repeated skin testing with PPD induced a detectable level of cutaneous sensitivity in normal guinea pigs. This sensitization appears enhanced in lymph node cell recipients.
Some Observations on the Immunochemistry of Dextrans
Authors: Coulson E. J. , Stevens Henry
Published: January 2023

Purified native dextrans, crude native dextran and clinical dextrans did not sensitize guinea pigs actively. Dextran sensitivity could be induced in guinea pigs by inoculation with Leuconostoc mesenteroides NRRL strains B-1374, B-1377, B-1424 and Leuconostoc dextranicum, strain B-1375. However, no sensitivity could be induced with Leuconostoc mesenteroides B-512(F). The sensitivity induced in guinea pigs by Leuconostoc mesenteroides could be inhibited by prior administration of dextran. Antidextran rabbit serum was produced by immunizing rabbits with Leuconostoc dextranicum B-1375 and Leuconostoc mesenteroides B-1424. Rabbits immunized with Leuconostoc mesenteroides B-512(F), without adjuvants, produced antiserum to a minor component of dextran, probably a somatic antigen. Rabbits immunized with B-512(F) with adjuvants produced antibodies both to dextran and to the minor component. The precipitating capacity of dextran with antiserum diminished with deceased molecular size. The lowest fraction with a molecular weight of 10,700 precipitated about one-half of the antibody content of the serum. Hydrolysis increased the shocking capacity of native dextran in passively sensitized guinea pigs. The most effective molecular size was between 41,600 and 35,400.
Enhanced Immunological Sensitization of Mice by the Simultaneous Injection of Antigen and Specific Antiserum
Authors: Terres Geronimo , Wolins William
Published: January 2023

Mice injected intravenously with BSA and rabbit anti-BSA serum in antigen excess show an accelerated immune response to the antigen. This immune response is related to the ratio of BSA to anti-BSA used in the initial injection. The optimal combination of BSA and anti-BSA is in slight antigen excess. Anaphylactic sensitization parallels the accelerated immune response in time of onset. This response to BSA is not related to bacterial contamination.
Immunological Studies on African Swine Fever Virus
Authors: Cowan Keith M.
Published: January 2023

The ProC′ activity of swine serum was abolished by treatment with dilute formalin. Sera treated in this manner fixed guinea pig C′ in the presence of antigen, but serum titers were somewhat depressed. Because of the prozoning activity of untreated swine sera, little or no indication of fixation occurred with some sera of low antibody content. However, removal of the ProC′ activity of these sera with formalin either abolished or markedly reduced the prozone effect so that a C′F reaction could be obtained.
Preparation and Properties of Partially Purified Erythrogenic Toxin B of Group A Streptococci
Authors: Stock Aaron H. , Lynn Raymond J.
Published: January 2023

Crude concentrates containing erythrogenic toxin B were prepared from filtrates or supernatants of cultures of three group A streptococci and the partially purified toxins were studied. Toxin B, like toxin A, appeared to be a protein and was not precipitable by protamine. Toxin B, unlike toxin A, was largely destroyed in the presence of trypsin. Toxin B, in contrast to toxin A, did not flocculate with anti-A antitoxin. In agar gel diffusion tests, a specific precipitin reaction of toxin B-anti-B antitoxin was not identified.
Permeability Changes Produced in Mice by Bordetella pertussis
Authors: Munoz J.
Published: January 2023

Various methods of demonstrating permeability changes produced in mice by B. pertussis were described. By measuring the amount of Evans blue that disappears from the circulation it was found that the increased permeability of capillaries can be demonstrated 1 day after the injection of B. pertussis and persists for at least 8 days. By the end of 16 days after the injection of B. pertussis, the permeability to Evans blue had returned to normal. A good correlation was found between permeability changes and the increased histamine sensitivity in B. pertussis-treated mice, although S. enteritidis endotoxin or B. pertussis endotoxin, which produce permeability changes as marked as B. pertussis cells, failed to increase the sensitivity to histamine. Adrenalectomy also increased the permeability of capillaries to Evans blue. The increase in permeability produced by B. pertussis could be prevented by pretreatment of mice with hydrocortisone. S. enteritidis endotoxin did not increase the susceptibility of mice to passively induced anaphylaxis, although it seems to have some enhancing effect on actively induced anaphylactic sensitization. The significance of these results is discussed.
A Sensitive and Accurate Plate Assay for Poliovirus Neutralizing Antibody
Authors: Burt Avril M. , Cooper P. D.
Published: January 2023

A sensitive gel diffusion method is described for the detection and assay of poliovirus antisera, based on extended diffusion of antibody from agar cups or fish-spine beads in an agar base layer before addition of an agar suspension of virus infected cells. The advantages, sensitivity, and accuracy of this method are compared with others in current use; it should be useful for rapid screening of sera from recently vaccinated individuals.
Complement Fixation and Ionic Strength
Authors: Levine Lawrence , Wasserman Eleanor , Mills Stanley
Published: January 2023

Experiments are described which measure the effect of ionic strength on C′ fixation. It has been demonstrated that C′ fixation by both protein and polysaccharide immune systems is enhanced by NaCl concentrations less than and inhibited by NaCl concentrations greater than 0.15 M. This enhancement or inhibition of C′ fixation by changes in NaCl concentrations appears to affect a reaction step subsequent to antigen-antibody aggregation and prior to C′3 participation.
Effect of Antibiotics on Intracellular Salmonella Typhosa
Authors: Hopps Hope E. , Smadel Joseph E. , Bernheim Barbara C. , Danauskas Joseph X. , Jackson Elizabeth B.
Published: January 2023

Cultures of L929 mouse fibroblast cells infected with the Ty 2 strain of Salmonella typhosa were regularly freed of infection by treatment for prolonged periods of time with synnematin and occasionally by treatment with other antibiotics. Failure to eradicate S. typhosa from the tissue cultures resulted when the experiment was terminated prematurely because of nonspecific death of the host cells or overgrowth of the cultures by antibiotic resistant organisms.

Several hypotheses are discussed concerning the capacity of S. typhosa to persist for long periods of time in antibiotic-treated cultures. Previously, emphasis has been placed on the unique properties of the living cell in protecting the invading organism in the presence of antibiotic. The metabolic state of the organism in the treated infected culture may also be an important factor in its survival in the presence of drug.
The Effect of Route of Inoculation upon Development of Antibody in Rabbits
Authors: Parks James J. , Leibowitz Howard M. I. , Maumenee A. E.
Published: January 2023

The results of the experiments described indicate that comparable titers of specific circulating antibodies are induced following inoculation of identical quantities of soluble antigen either intracorneally or intravitreously. These titers, in turn, are comparable with those induced when the same quantity of antigen is incorporated in adjuvant and injected intramuscularly. These three methods of antibody induction have in common two basic mechanisms: a) slow diffusion of antigen from the site of inoculation and, b) the infiltration of the inoculation site with cells involved in the production of antibody. The use of avascular ocular routes in experimental immunization schedules in animals is suggested if antigen is scarce or if the use of an adjuvant is not desired.
Staining of Vaccinia-Infected L Cells with Brilliant Cresyl Blue
Authors: Zebrowski Leon , Smith K. O. , Sharp D. G.
Published: January 2023

Although over 95% of normal L cells in cultures 3 to 5 days old are stained by brilliant cresyl blue, cells infected with vaccinia virus tend to remain unstained. This tendency may develop 2 hr after infection and increase to involve most of the cells.
Studies on the Complement-Fixing Antigens of Poliomyelitis
Authors: Hinuma Yorio , Hummeler Klaus
Published: January 2023

Comparison of three methods of fluorescent antibody staining revealed the complement staining procedure to be the best method available for the virus-antibody system under investigation. The procedure showed good correlation to results obtained in the in vitro complement fixation test and could be applied quantitatively for maximum specificity and sensitivity.

Drying of infected cover slip cell cultures, prior to fixation, resulted in total conversion of existing N to H antigen, which is, nevertheless, typespecific.

Investigation of intracellular synthesis of specific antigen, by the complement staining method, and simultaneous assay of production of mature virus, led to the conclusion that both begin at the same time, from 2 to 3 hr after infection depending on the multiplicity of infection employed. Near or at the completion of the infectious cycle, about 300 plaque forming units of virus were produced per fluorescent cell
Destruction of Lymphocytes in Vitro by Normal Serum from Common Laboratory Animals
Authors: Terasaki Paul I. , Esail Marian L. , Cannon Jack A. , Longmire William P.
Published: January 2023

Normal serum from various animals has been shown to be toxic to lymphocytes and peritoneal exudate cells of various other animals. This toxicity could best be shown with fresh serum or in some cases only with fresh serum. Serum heated at 56°C for 30 min lost its activity in most instances. The activity lost upon storage or heating could not be completely restored by the addition of fresh homologous or autologous serum. Some particularly toxic combinations of serum-lymphocytes were: human-rabbit; human-mouse; rabbit-chicken; rabbit-rat; rat-chicken; chicken-rabbit; and chicken-guinea pig.
Studies on the Virus of Venezuelan Equine Encephalomyelitis
Authors: Gleiser Chester A. , Gochenour William S. , Berge Trygve O. , Tigertt William D.
Published: January 2023

In Macaca mulatta, infection with the Trinidad strain of VEE virus produced a benign, febrile illness with no clinical evidence of CNS involvement. Histologic alterations in the brains of these animals were limited to lymphocytic perivascular cuffing and to focal infiltration with glial cells. Morphologic evidence of neuronal injury was rare and, when seen, was limited to cells within the glial nodules. Both of these inflammatory responses were markedly suppressed by the administration of cortisone acctate, but only when the drug was given for the first time during the period of secondary fever. When cortisone was begun prior to inoculation and continued during the febrile period suppression of the inflammatory responses did not occur. In neither instance was drug administration found to modify the clinical disease nor to modify materially the eventual antibody response.
A Comparison of the Yields of Infectious Ribonucleic Acid from Heated and Ultraviolet Irradiated Mouse Encephalomyelitis Virus (GDVII Strain)
Authors: Nakamura Masahiro
Published: January 2023

An infectious RNA was extracted from mouse brains infected with Theiler's mouse encephalomyelitis virus (GDVII strain). The yield of infectious RNA from heated virus was compared to that from u.v. irradiated virus material and at the same time, the stability of the hemagglutinating activity of the virus with respect to heat and u.v. irradiation was investigated. The results obtained suggest that inactivation of virus by heat is due, in large part, to denaturation of virus protein whereas inactivation by u.v. irradiation is due to destruction of viral RNA without denaturation of protein.
Suppression of Transferred Lymph Node Cells by Rabbit-Antirabbit Leukocyte Serum
Authors: Harris T. N. , Harris Susanna , Farber Miriam B.
Published: January 2023

It was shown earlier that if rabbits given rabbit lymph node cells incubated in vitro with Shigella antigen were injected with pooled rabbit-anti-rabbit leukocyte serum, the production of anti-Shigella agglutinins in these recipients was reduced in comparison with recipients given the cells alone. In the present study a number of further observations have been made on the production of such antileukocyte sera, and their effects when incubated with lymph node cells prior to the transfer of these cells.

When antirabbit leukocyte sera obtained after a single intradermal injection of leukocytes were incubated with rabbit lymph node cells prior to transfer of the cells, reduction of the level of agglutinin titers of these recipients was found. For each such serum pool there was a range of amounts within which the degree of suppression of the transferred lymph node cells was a function of the amount of such serum with which the lymph node cells had been incubated prior to transfer. In the case of sera obtained after a second injection of rabbits with rabbit leukocytes, such a relation could also be observed, the sera being approximately 10 times as effective as sera obtained after a single injection of pooled leukocytes. Sera obtained after intradermal injection of rabbits with rabbit leukocytes were more effective in suppressing the transferred lymph node cells than those obtained by intravenous injection of such leukocytes. Removal of excess antileukocyte serum by centrifugation and washing of the lymph node cells did not affect the degree of suppression of these cells. When the lymph node cells were obtained from donor animals injected with Shigella the suppressive effect of the antileukocyte serum on the transferred cells was clearly observed, even when the cell transfer was performed within a day of the expected time of appearance of antibody in the recipient animals. The injection of rabbit-antirabbit leukocyte serum into recipients after the transfer of antigenincubated lymph node cells caused a decrease in the titer of agglutinins to Shigella. This was demonstrable even when the serum was injected 3 days after cell transfer, or within a day of the time of appearance of the antibody in the recipients' sera.
Molecular Bases of Passive Sensitization
Authors: Ishizaka Kimishige , Ishizaka Teruko , Sugahara Takao
Published: January 2023

The effect of chemical procedures designed to break the disulfide linkages of γ-globulins on passively sensitize guinea pig skin was studied with a human γ-globulin-rabbit anti-HGG system. Human (antigen) and rabbit (antibody) γ-globulins lost sensitizing activity after treatment with mercaptoethanol followed by sulfhydryl blocking agents such as iodoacetate or iodoacetamide, as determined by passive cutaneous anaphylaxis tests in guinea pigs. Treatment with either mercaptoethanol or iodoacetate alone did not affect their sensitizing activity. Mercaptoethanol-iodoacetate treated proteins, either as antigen or antibody elicited cutaneous anaphylactic reactions in guinea pigs previously sensitized with unmodified γ-globulins as antigen or antibody and also showed precipitin reactions with the complementary reagents comparable to reactions using unmodified proteins. The complement-fixing properties of the HGG-anti-HGG systems were unaffected by the treatment of either antigen or antibody by mercaptoethanol and iodoacetate. The results suggested that irreversible cleavage of disulfide linkages in human and rabbit γ-globulin molecules was correlated with a decrease in their affinity for guinea pig tissues.
The Effects of Pretreatment with X-Rays on the Pathogenesis of Lymphocytic Choriomeningitis in Mice
Authors: Collins Doris N. , Weigand Heribert , Hotchin John
Published: January 2023

LCM virus inoculated i.c. in mice produced lethal meningoencephalitis and hepatitis. However, x-irradiation of mice with 500 r 24 hr before inoculation with LCM i.c. prevented the development of characteristic lesions and fatal disease. The host response to irradiation in the presence of the virus was similar to that of controls which had received irradiation only. The effect of x-radiation of this dosage was depression and destruction of existing blood cells of the hematopoietic system without damage to the mechanism for regeneration; at the same time, it caused the elimination of the pathological changes normally associated with LCM infection. It is concluded that the irradiation eliminates a host cellular immune response, which is responsible for disease due to this virus.
Protection of Chick Embryos Against Newcastle Disease Virus by Trypan Blue and Other Compounds
Authors: Finkelstein Richard A.
Published: January 2023

Of a number of related compounds tested, Trypan blue, Evans blue, Pontamine sky blue, Trypan red, Congo red and Erie garnet B protect chick embryos against Newcastle disease virus. Although the first four dyes block hemagglutination of NDV, the latter two do not, but they apparently interfere with elution of adsorbed virus. All the active compounds tested are acid, bis-azo dyes with diphenyl and naphthalene residues with two or more sulfonic acid groups. The latter two compounds have the simplest molecular structures.

Trypan blue was also demonstrated to inhibit NDV in cultured mammalian cells. However, it could not be shown to have an effect on influenza virus.
A Method of Purifying Coxiella Burnetii and Other Pathogenic Rickettsiae
Authors: Ormsbee Richard A.
Published: January 2023

A method of readily purifying large amounts of rickettsiae by means of differential, continuous flow centrifugation from molar salt solutions followed by ether treatment has been described.

This technique has been applied to Coxiella burnetii, Rickettsia rickettsii, Rickettsia prowazekii, and Rickettsia mooserii.

Purified preparations of C. burnetii and R. rickettsii prepared in this manner have been shown to possess, when tested as vaccines, protective qualities fully equal to those of conventional rickettsial vaccines.
A Study of the Antibodies in Guinea Pigs Infected with Foot-and-Mouth Disease Virus
Authors: Cartwright B.
Published: January 2023

Antiserum to the virus of foot-and-mouth disease appears to contain at least two antibodies. The purified 25-mµ infective component of the virus has sites capable of combining with each antibody, whereas the noninfective 7-mµ component combines with one antibody only. The complement-fixing activity of an antiserum is the sum of two separate antibody activities to the 7-mµ and 25-mµ viral components and is not related in a simple way to the virus-neutralizing activity of the serum. The ratio of the complement-fixing activities of the antibodies to the 7 mµ and 25 mµ component of the virus is greater when adjuvant is used with the hyperimmunizing dose.
Hemagglutination and Hemagglutination-Inhibition Studies with Echo Viruses
Authors: Bussell Robert H. , Karzon David T. , Hall Frances T.
Published: January 2023

A study of several factors which may affect hemagglutinin (HA) production revealed that a dilute inoculum combined with a relatively late harvest time favored maximum HA titers of ECHO 6 viruses grown in monkey kidney tissue culture. Infectivity to HA ratios of 6 to 7 logs were obtained with viruses which attain high infectivity titers (B phase), while the ratios obtained with the low titer viruses (S phase) were approximately 4 to 5 logs. A survey of ECHO 6 strains revealed that 9 of 24 tested produced HA. HA production could not be correlated with infectivity titers, phase, or number of passages in tissue culture. Cross hemagglutination-inhibition (HI) tests with hyperimmune rabbit antisera revealed a high degree of specificity among the serotypes tested. Differences were noted among several ECHO 6 HA antigens in their ability to detect HI antibody. Nonspecific inhibition of ECHO virus hemagglutination was demonstrated. Adsorption of sera with 0.1% bentonite resulted in almost complete removal of nonspecific inhibitors, whereas this procedure had no apparent effect on specific HI antibody.
Hemagglutination-Inhibiting, Complement-Fixing and Neutralizing Antibody Responses in Echo 6 Infection, including Studies on Heterotypic Responses
Authors: Bussell Robert H. , Karzon David T. , Barron Almen L. , Hall Frances T.
Published: January 2023

The development and persistence of ECHO 6 neutralizing, complement-fixing (CF) and hemagglutination-inhibiting (HI) antibodies was studied in 24 aseptic meningitis patients from whom an ECHO 6 virus was isolated. The neutralization test yielded the greatest number of significant antibody rises (96%), the HI or CF tests yielded significant rises in 67% of the patients. The three types of antibody reached peak levels by the 2nd week after onset of illness. Neutralizing antibody persisted with little or no decline for 3 years, HI antibody declined rapidly and then persisted at significant levels for 3 years, and CF antibody was undetectable or at low levels 3 years after onset. Cross serologic tests among small groups of ECHO 4, 6 and 9 patients revealed the neutralization and HI tests to be fairly specific, while a significantly greater number of heterotypic reactions were obtained with the CF test. Evidence was presented which indicates a relationship between the heterotypic CF responses and a prior infection with the heterotype.
Endotoxin and Its Relationship to Anaphylaxis in the Mouse
Authors: Einbinder Julia M. , Nelson Carl T. , Fox Charles L.
Published: January 2023

Endotoxins isolated from Gram-negative organisms have been shown to modify the response of experimental animals to various forms of injury such as thermal burns (1), hemorrhage (2), tourniquet (3), whole body irradiation (4), anaphylaxis (5), or massive bacterial (6) or viral infections (7). Depending on circumstances, the endotoxins may enhance the mortality or offer protection from the fatal outcome of the injury. This report describes some effects of an endotoxin on anaphylaxis in mice.

Materials and Methods. The endotoxin used was the lipopolysaccharide of Escherichia coli purchased from the Difco Company. White, Swiss, female mice weighing 18 to 20 g were sensitized by intraperitoneal (i.p.) injections of normal horse serum every other day for a series of four injections, and were challenged intravenously 21 days after the first sensitizing injection, as described previously (8). Tolerance to endotoxin was produced by a series of five daily injections starting with 25 mµ of endotoxin and then increasing each injection by 25 mµ.
The Production of Anti-Human Leukemic Serum in Rabbits
Authors: Garb Solomon , Stein Arthur A. , Sims George
Published: January 2023

Injection of normal human blood constituents into neonatal rabbits resulted in immunologic tolerance to those constituents. Subsequently, the rabbits were immunized with a series of injections of buffy coat from patients with granulocytic leukemia. Tests of these rabbits' serum were done in Ouchterlony plates, and in most cases, showed a response to buffy coat from patients with acute myelogenous leukemia, without a comparable response to normal human buffy coat. Skin tests generally confirmed the Ouchterlony plate findings. It appears that buffy coat from patients with acute myelogenous leukemia is adequate both for inducing heterologous antibody formation, and for combining with such antibodies in the test situations used. On the other hand, buffy coat from patients with chronic myelogenous leukemia appears to be adequate only for inducing heterologous antibody formation, but not for combining with such antibodies in the test situations used. Some of the implications of these observations are discussed.
A Study on Toxic Effect of Vaccinia Virus in Mice with Special Reference to Hematological Changes
Authors: Zakay-Roness Z. , Rosin A. , Bernkopf H.
Published: January 2023

High concentrations of vaccinia virus caused death of i.v. inoculated mice within 15 to 24 hr. No multiplication of virus could be demonstrated in the organs of the inoculated animals.

Characteristic findings were: a drop of 50% or more in the normal erythrocytes counts within 10 to 12 hr, leukocytosis and lymphocytopenia. Histological examination of the organs revealed a number of changes, most prominent among them were severe hemorrhages in the liver. A toxic effect of the virus seemed to be responsible for the reported findings.
The Conversion of Precipitating to Nonprecipitating Antibody in Immune Sera of the Guinea Pig
Authors: Pruzansky Jacob J. , Feinberg Samuel M.
Published: January 2023

Several guinea pig precipitating immune sera, heated at 56°C for 30 min, no longer precipitated with homologous antigen. Heated sera were capable, however, of coprecipitation with homologous unheated serum and antigen, sensitizing guinea pigs to anaphylaxis, precipitation in liquid medium at pH 5, precipitation in agar gel at pH 5, 7 or 8.5, and hemagglutination. The presence of albumin globulin complexes in heated guinea pig immune serum could not be demonstrated. Guinea pig albumin was not detected immunologically after dissolving in excess antigen the precipitate formed by coprecipitation of heated antiserum with unheated antibody and homologous antigen.
The Inhibition of Hemagglutinin Formation in Mice by Purine and Pyrimidine Analogues
Authors: Frisch Arthur W. , Davies Gordon H.
Published: January 2023

Screening experiments with 30 selected purine and pyrimidine analogues have revealed five compounds which inhibited hemagglutinin production in mice. Of these, 6-mercaptopurine, 6-mercaptopurine riboside, 2-amino-6-benzylmercaptopurine and 2-amino-6-(1′-methyl-4′-nitroso-5′-imidazoyl) mercaptopurine were classed as slightly active. One of the compounds, thioguanine, was found to be highly active in toxic doses. 6-mercaptopurine did not inhibit hemagglutinin formation in rabbits given a dose of 6 mg/kg for 13 days when either human or sheep red blood cells were used as antigen. In groups of mice also, 6-MP, at a dose level of 25 mg/kg, failed to prevent hemagglutinin formation. Thioguanine, however, in doses of 5 and 2.5 mg/kg, but not 1 mg/kg, blocked primary hemagglutinin production. With single animals, the inhibiting effect of thioguanine was uniformly evident; with 6-MP, variations were observed among individual mice. The data are discussed in relation to previously published studies on 6-MP.
Virus Particle Aggregation and the Plaque-Forming Unit
Authors: Galasso G. J. , Sharp D. G.
Published: January 2023

Dilute suspensions of vaccinia virus, prepared in various ways, have been sedimented upon a smooth surface and examined by electron microscopy. The observed aggregation, probably similar to that which exists in plaque titration experiments, is found to involve usually over 60% and often over 90% of the particles. Sonic waves are found to be more effective than repeated freezing and thawing, enzymes or pipetting for dispersal of aggregation among the virus particles. This comparison is done by counting and expressing as a percentage of the total count, the number of groups or potentially active units seen in the pictures. The rate of reaggregation of dispersed suspensions was similarly measured.

Plaque titration shows the effects of dispersive agents which increase the percentage of active units (AU) and of plaques as well, whereas the total virus particle count remains unchanged. The observed increase in plaques (84% in one experiment) is less, however, than the corresponding increase in AU. This is attributed to the fact that only a small fraction of the virus particles are capable of producing plaques.
Studies on the Kinetics of Histamine Release from Normal and Sensitized Tissues
Authors: Nielsen Christen B. , Feigen George A.
Published: January 2023

The present views concerning the manner in which antigens release histamine from sensitized tissues fall into two principal categories embodied either by the enzymatic hypothesis or the displacement hypothesis. The relative merits of these views have been discussed at length in a recent article by Üvnas (1).

In order to clarify some of the problems concerning the mechanism of histamine release from tissues by immunological reactants, it is necessary to know what proportion of the total tissue histamine is released immunologically, the kinetics governing release by specific and non-specific agents, the rate of restoration of histamine in the tissue, and whether other substances are concomitantly liberated. The solution of these problems could be significantly facilitated if the antibody concentration on the tissue could be brought under experimental control, and if the site and method of attachment of antibodies to vulnerable cells were known.
The Effect of Total Body X-Irradiation of the Rabbit on the Rejection of Homologous Skin Grafts and on the Immune Response
Authors: Brooke Marcus S.
Published: January 2023

The effect of sublethal (400 r), midlethal (600 r), and near-lethal (1100 r) total body irradiation on the ability of rabbits to reject homologous skin grafts, to develop delayed hypersensitivity, and to form circulating antibodies to bovine γ-globulin and sheep erythrocytes was studied. Different intervals were allowed to elapse between x-irradiation and the presentation of antigens.

Maximum prolongation of skin graft rejection time occurred with 400 r when grafting was done on the same day as irradiation. A 2-fold increase in the median rejection time was observed, and the occasional animal retained its graft for as long as 7 to 10 times the normal. No great advantage appears to be gained by increasing the radiation dose from 400 to 600 r and it is possible that prolongation of skin graft rejection time by irradiation can be as well obtained with a sublethal as with a midlethal dose of irradiation. The time between irradiation and grafting appears to be as critical as the dose of irradiation.

The temporal results with the other antigens were similar to those with skin grafts.
An Inhibitor of Adenoviruses in OX Serum
Authors: Gold Eli , Ginsberg Harold S.
Published: January 2023

The presence of pooled, heated on serum in media inhibited the propagation of several types of adenovirus in HeLa cell tissue cultures. The greatest decrease in infectivity titer occurred with types 4, 5 and 7 adenoviruses. The inhibitor in normal ox serum was a heat-stable globulin which formed a nondissociable complex with the infectious virus particle and was not destroyed by RDE or trypsin. Although this inhibitor has many characteristics of neutralizing antibody, the observation that absorption of ox serum with type 3 adenovirus removed the inhibitor against both types 3 and 4 adenoviruses to a similar extent indicates that the inhibitor is not a mixture of several types of neutralizing antibody.
Phagocytosis of Particulate Complexes of γ-Globulin and Rheumatoid Factor
Authors: Parker Robert L. , Schmid Frank R.
Published: January 2023

Precipitates formed by the interaction of rheumatoid sera and fluorescent γ-globulin were ingested by viable leukocytes. This reaction required preliminary heating of the γ-globulin. The results suggest that the reactive portion of the γ-globulin is in the form of aggregates. The phenomenon of phagocytosis demonstrates a new biologic property of rheumatoid factor-γ-globulin precipitates and illustrates another resemblence of these precipitates to antigen-antibody complexes.
Quantitative Analyses by Diffusion Column Reactions
Authors: Glenn William G.
Published: January 2023

An automatic cathetometric instrumentation that objectively interpolates and prints diffusion measurements to 0.001 mm has been implemented for reading agar column reactions. Based on 672 separate readings on duplicate SD columns for serum albumin, a cathetometric sighting error (σe) was estimated as 0.036 mm for one investigator; the column to column component of variation (σc) was 0.185 mm. When duplicate SD columns were measured once each several times during the reaction period, another component of variation, was detected. This, pooled with σe and σc, was estimated as 0.143 mm for 1154 measurements on fractions (II, V)-antifraction reactions. As a general guide—under specific conditions for measurement, time, and temperature—for the mean of one measurement on each of two SD columns to achieve statistical significance over a similar statistic for another reaction, the diffusion difference should equal or exceed 1.96 (0.143 mm) = 0.280 mm (5% probability level) in absolute value. (The normal deviate value, 1.96, pertains only to studies involving, as in this instance, a large number of measurements.)
Specific Cation Effects with Antibody to a Hapten with a Positive Charge
Authors: Grossberg Allan L. , Chen Chun-Chuen , Rendina Leonard , Pressman David
Published: January 2023

The binding of homologous hapten by antibody to the positively charged p-azophenyltrimethylammonium ion was found to be decreased by inorganic cations but not by anions. This appears due to the competition of the cations with the hapten for the negative charge in the specific site of the antibody molecule.

The order of effect for singly charged cations is Cs+ > Rb+ > NH+4 ≥ K+ > Na+ ≥ Li+, which is in the order of the ionic radii and the inverse order of the radius of the hydrated ions. For doubly charged cations the order is Ba++ > Ca++ > Mg++.