bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of Rabbit Antibody Frangments
Authors: Stelos Peter , Radzimski Gerald , Pressman David
Published: January 2023

The reaction of radioiodine with fragments obtained by papain digestion of rabbit γ-globulin or rabbit antibody has been studied. The γ-globulin digests were examined in the ultracentrifuge and consisted of a single peak with a sedimentation coefficient of 3.5 S. The γ-globulin digests were separated into three major fractions by chromatography on carboxymethyl cellulose columns and were analyzed for radioiodine and protein. In preparations containing whole γ-globulin, Fractions I and II iodinated to about the same extent, whereas Fraction III iodinated to about half the value of I and II. These values were found whether iodination preceded digestion or the reverse.

Results with specifically purified antibody (against the p-azophenylarsonate group) differed from the results obtained with whole γ-globulin in three respects: a) The amount of protein in Fraction II was about twice that of Fraction I. b) Fraction II was iodinated at a level 25 to 30% greater than Fraction I. These two findings are interpreted as indicating that Fractions I and II are derived from different antibody molecules rather than representing the two parts of the same antibody molecule. c) Differences were also observed in the relative iodine contents of the three fractions of specifically purified antibody, depending on whether iodination preceded or followed digestion, indicating differences in orientation of the components of the original antibody molecules.
Immunological Studies on Rat Parabiosis
Authors: Milgrom Felix , Müller-Ruchholtz Wolfgang , Witebsky Ernest
Published: January 2023

Parabiosis was established between unrelated female albino rats weighing 140 to 200 g, according to the technique of Bunster and Meyer. All serological tests performed in vitro for the detection of antibodies against antigens present in rat erythrocytes, leukocytes, serum, and various organs were negative, or at least not conclusive.

In contrast, sera of 37 out of 91 parabiotic rats induced skin reactions when injected intradermally into normal test rats. The skin reactions became visible after intravenous administration of Evans blue.

The skin reaction producing factor (SRPF) was to be found in the serum as early as 5 to 15 days after parabiotic union. The individuality of the skin-tested animal was of primary importance in obtaining positive reactions, necessitating the examination of more than one test animal for each serum under investigation.

The parabiotic animals sometimes, but not always, exchanged their SRPF. The passively transferred SRPF originating from the partner's serum disappeared within 2 to 3 weeks after the separation of the animals, whereas the actively produced SRPF persisted up to 8 weeks.

On the basis of the experimental data presented, the SRPF was considered an isoantibody directed against group-specific tissue antigens of the parabiotic partner.
Fate of H3-Thymidine-Labeled Spleen Cells in in Vivo Cultures during Secondary Antibody Response
Authors: Capalbo Elmo E. , Makinodan T. , Gude W. D.
Published: January 2023

Labeled donor spleen cells colonized preferentially in the hematopoietic tissues of heavily irradiated, isologous recipient mice. More labeled cells were detected in the spleen and bone marrow than in the lymph node and thymus, and more were seen in the latter tissues than in the liver, lung, and small intestine. These results suggest that spleen cells have a “homing instinct” in irradiated recipients.

Studies on the proliferative capacity of donor-labeled lymphoidal cells in the recipient spleen (H3T-Index and mean grain count/cell) indicate that the maximum mean generation time of these cells can be shortened 2-fold when stimulated by an antigen from ∼24 to ∼12 hr. This accelerated rate of proliferation occurs 2 days before the appearance of antibody in the circulation. The results, furthermore, suggest that mature plasma cells, following an antigenic stimulation, are derived from three to four cellular divisions.
Heterogeneity of the Major Fractions of Papain Digests of Rabbit Antibody
Authors: Stelos Peter , Roholt Oliver , Pressman David
Published: January 2023

Papain digests of specifically purified rabbit antibodies against the p-azobenzenearsonate and the p-azobenzoate groups were chromatographed using a gradient which differed from that described by Porter. A preparation of γ-globulin from nonimmunized rabbits was similarly digested and chromatographed.

The results indicate the presence of more types of antibody and γ-globulin fragments than the three originally found by Porter.
Studies with Tissue Culture-Modified Rinderpest Virus as an Immunizing Agent
Authors: De Boer Carl J.
Published: January 2023

Serial passaging of the Kabete O strain of rinderpest virus in calf kidney tissue cultures resulted in modification of its virulence for cattle. Although inoculation of cattle with nonmodified virus resulted in development of the disease and death, inoculation with the modified virus was accompanied by development of antibodies. The only clinical sign was a mild rise in temperature. Inoculation of groups of cattle with the modified Kabete O virus afforded protection against challenging dosages of 105 and 106 LD100 of the Kabete O, the Pak Chong, and the Pendik strains, respectively. Such cross-immunity indicated that all three strains share a broad common antigenic factor. The modified virus was not spread from inoculated cattle to normal ones by contact.
The Mechanism of Particulate Carrier Reactions
Authors: Singer Jacques M. , Oreskes Irwin , Altmann Gideon
Published: January 2023

Examination of 16 commercial preparations of HGG revealed great variability in their capacity to sensitize tanned sheep erythrocytes for agglutination with RAS. Sodium sulfate fractionation of one whole γ-globulin revealed that sensitizing capacity was largely in the aggregated fraction and that the 7 S fraction was a very poor sensitizer.

Tanned sheep cells were found to adsorb HGG in amounts proportional to the concentration of the added protein. Logarithmic plots of amounts adsorbed against amounts added were linear and corresponded to a Freundlich type of adsorption isotherm. Under the conditions of the FII coated tanned sheep cell procedure and with a sensitizing amount of 1000 µg N, one tanned sheep red cell adsorbed about 5 × 105 HGG molecules.

Both 7 S HGG and aggregated HGG were adsorbed to tanned sheep cells, and the corresponding isotherms were very similar even though only aggregated HGG could sensitize tanned sheep cells for agglutination with RAS. Maximum titers were observed at a sensitizing level of 5 × 104 aggregated HGG molecules adsorbed/red cell.

RAS agglutination titers increased to a limiting value, with increasing adsorption of HGG to tanned sheep cells. Beyond this limiting titer, adsorption of further HGG by the tanned sheep cells occurred without effect on the titer.
Influence of Vaccination on Respiratory Coccidioidal Disease in Cynomolgous Monkeys
Authors: Levine H. B. , Miller R. L. , Smith C. E.
Published: January 2023

Five of ten Cynomolgous monkeys (Macaca irus) died and two were moribund within 9 months after respiratory infection with 200 coccidioidal arthrospores. None of seven animals previously vaccinated with formalinized spheruleendospore elements of the fungus succumbed to the above dose but one vaccinated animal challenged with approximately 400 arthrospores died within a 7-week period. It was demonstrated that both early and late roentgenographic changes in the lungs were less extensive in the vaccinated group than in the control group and these observations were in accord with pathologic findings at necopsy. The etiologic agent was recovered from the lungs of all surviving animals but histopathologic studies suggested that the parasite was contained more effectively within lesions in the vaccinated monkeys.
The Inhibition of Hemagglutinin Formation in Mice by Thioguanine
Authors: Frisch Arthur W. , Davies Gordon H. , Milstein Victor
Published: January 2023

Thioguanine at a dose of 2.5 mg/kg was shown to be an effective inhibitor of the primary hemagglutinin response in both mice and rabbits. Similarly, 6-MP at a level of 15 mg/kg, prevented the formation of sheep cell hemagglutinins in rabbits. In mice, evidence of suppression was obtained with doses of 2.5 mg/kg begun on the first and second day following antigenic stimulation; a single subcutaneous injection of 75 mg/kg of TG was also effective if administered during the same intervals. Prolongation of the induction phase and depression of established hemagglutinin titers were evident in mice receiving 75 mg/kg of TG 2, 4 and 8 days after primary immunization. Pretreatment with TG for 2 and 5 days prior to antigen injection was ineffective. The secondary hemagglutinin response in mice was also suppressed by TG, provided the drug was given during the first 2 days following antigenic stimulation.
The Effects of Alloxan Diabetes on Phagocytosis and Susceptibility to Infection
Authors: Wertman Kenneth F. , Henney Mary R.
Published: January 2023

Male albino rats of the Sprague-Dawley strain were injected with varying amounts of alloxan and the following studies were made: a) blood sugar determinations, b) susceptibility to Staphylococcus aureus, c) the phagocytic activity of the leukocytes, and d) differential cell counts of the peripheral blood. Adequate numbers of control animals were included.

The following observations were made from these studies: Rats that received 20 mg or less of alloxan/kg of body weight failed to develop significant amounts of blood sugar. Approximately 50% of the rats injected with 30 mg of alloxan/kg of body weight failed to develop significant blood sugar levels but the remainder of this group and the animals that received 40 mg of alloxan/kg of body weight developed significantly higher blood sugar levels.The rats with high concentrations of blood sugar were more susceptible to the challenge injection of Staphylococcus aureus than those with low concentrations.The percentage of neutrophils actively engaged in phagocytosis was considerably less in the diabetic rats and the average number of organisms phagocytized by these cells was considerably less than by the cells of the normal control animals.The differential cell counts of the peripheral blood of the alloxan diabetic rats and the controls were within normal range.
Q Fever Antibody Response in Experimentally Infected Wild Rodents and Laboratory Animals
Authors: Sidwell Robert W. , Gebhardt Louis P.
Published: January 2023

Capillary tube agglutination antibody and Phase I and Phase II complement fixation antibody to Coxiella burnetii was studied in five species of experimentally infected wild rodents, and in guinea pigs and white mice. Phase II CF antibody was produced 1 to 2 weeks following i.p. infection of the California AD strain of C. burnetii in all species of animal tested. Peak titers were reached 3 to 5 weeks after infection. Phase I CF and CT agglutination antibody was first demonstrated at 3 to 5 weeks, increasing to peak titers at periods of time varying from 6 to 36 weeks after infection, depending upon the animal species. Phase II CF titers were higher in all animals than Phase I CF or CT agglutinating antibody titers. Persistence of titers was followed for 36 or 52 weeks, depending upon animal type. Ord kangaroo rats produced little demonstrable Phase I CF or CT agglutination antibody.

All species of wild rodents injected with formalin-inactivated AD strain of C. burnetii produced low titers of Phase II CF antibody in studies through 16 weeks after inoculation. Phase I CF antibody was barely demonstrable in desert wood rats, Ord kangaroo rats, and pinyon mice. No detectable CT agglutination antibody was formed.

No antibody could be demonstrated in five species of wild rodents 28 days after injection with normal egg yolk sac material.
Immediate Hypersensitivity Reactions in the Cornea of the Guinea Pig
Authors: Parks James J. , Leibowitz Howard M. I. , Maumenee A. Edward
Published: January 2023

Guinea pigs sensitized to a stage of Arthus skin response developed corneal opacification following careful intracorneal injection of small doses of the inciting protein antigen.

The “Wessely ring,” representing precipitated antigen-antibody complexes and inflammatory cells in the avascular cornea, is rarely seen as a primary manifestation of immediate corneal sensitivity in the guinea pig. More commonly, a diffuse interstitial clouding accompanied by a limbal inflammatory response is seen. This must not be interpreted as a manifestation of delayed sensitivity since it can be reproduced passively with humoral antibody.

An identical quantity of Evans blue dye is more rapidly removed from the cornea of the guinea pig than from the cornea of the rabbit. The anatomic make-up of the normal guinea pig's cornea is believed to account for this discrepancy.
Characteristics of Endotoxin Altering Fractions Derived from Normal Human Serum
Authors: Yoshioka Morimasa , Johnson Arthur G.
Published: January 2023

Alcoholic fractionation of normal human defibrinated plasma by Cohn's method 10 resulted in two fractions capable of altering bacterial endotoxins. Incubation of endotoxin in the first, Fraction IV1, resulted in a marked reduction of the ability of specific antiserum to precipitate endotoxin. In addition, the capacity of the lipopolysaccharide to elicit a pyrogenic response in rabbits was abolished. A second fraction, III0, as isolated, was generally incapable of such effects unless it was activated by several procedures. All other fractions did not affect these properties of endotoxin. Alteration of the lethal activity of endotoxin was not evident after incubation in Fraction IV1, but was reduced after exposure to activated Fraction III0. The characteristics of these reactions are recorded.
Studies on the Chemotherapy of Viral Infections
Authors: Engle Claire G. , Liu Oscar C.
Published: January 2023

Three compounds containing the ketoaldehyde moiety were studied for activity against the PR8 strain of influenza A virus in vitro and in various embryonated egg systems. These compounds were p - (p - phenylphenacylideneamino)benzoic acid (8949); 4,4′-biphenyldiglyoxylaldehyde, dihydrate (8234); and p-(α-ethoxy-p-phenylphenacylamino)benzoic acid (8318). All were found to be virucidal against the virus in vitro. When these compounds were suspended in 25% heat-inactivated calf serum, the virucidal effect was diminished by approximately 30- to 100-fold. Also, the virucidal effect was reduced by mixing compound with allantoic fluids in vitro or directly in ovo. All compounds were shown to be effective against the PR8 virus in ovo when the compounds and the challenge virus were given by the allantoic route. However, suspending 8234 in 25% calf serum did not impair its activity in intact eggs. Both 8234 and 8318 were studied in de-embryonated eggs using the one-step growth curve technique. A suppression of the hemagglutinins present in the fluids as well as that contained in the allantoic membrane was observed in the treated as compared with the untreated controls when initial treatment with these compounds was begun as early as 0 to 6 hr or as late as 11 to 12 hr postinfection. Thus, these compounds were shown to have both a virucidal and virustatic effect.
A Comparative Study of the Incidence of Anergy in Patients with Carcinoma, Leukemia, Hodgkin's Disease and Other Lymphomas
Authors: Lamb Donald , Pilney Frank , Kelly William D. , Good Robert A.
Published: January 2023

Delayed hypersensitivity to a battery of six microbial antigens and one control solution was tested in 400 patients, including 208 controls and 192 with Hodgkin's disease, carcinoma, leukemia and non-Hodgkin's lymphoma. Fifty-three per cent of the Hodgkin's disease group were anergic early in the course of the disease, in contrast to the low incidence among the other patient groups judged to be in good condition on clinical grounds. Anergy was more frequent in all groups when the disease was advanced and the general physical condition of the patients was regarded as poor. Possible mechanisms and significance of this anergy are discussed.
Studies on Japanese B Encephalitis Virus Vaccines from Tissue Culture
Authors: Rohitayodhin Skon , Hammon W. McD.
Published: January 2023

The Nakayama mouse adapted strain of JBE virus was carried 50 passages at 37°C in HKC culture in “rapid passage” of a large inoculum and 32 passages including several series of terminal dilution passages. No marked differences were noted in the ratio of the tissue culture titers to the mouse titer through either of these series, although some slight change probably occurred in the rapid passage lines. Some reduction in suckling mouse pathogenicity via the subcutaneous route occurred in this same rapid passage line. Several passages of each of these lines at lower temperatures failed to give any indication of any further substantial reduction in mouse virulence.

A virus strain, OCT-541, isolated directly in HKC cultures from wild caught mosquitoes was carried from 15 to 60 passages in nine different HKC rapid passage lines, most of which included reduction of incubation temperature. Comparisons of mouse titers and HKC titers at 37°C and sometimes at 24°C were made at intervals of five passages. These revealed a somewhat greater ratio of titer between the mouse and tissue culture than that observed for the Nakayama strain. The line (35–24) carried five passages at each reduction step in temperature, i.e., 35°, 33°, 30°, 27° and 24°, then continued at 24°, gave greatest promise. A very significant change occurred in the average survival time of mice. This line lost its ability to infect or be transmitted by Culex tritaeniorhynchus by the 20th passage, but retained its ability to produce viremia in chicks. It failed to infect or to produce disease in suckling mice by the subcutaneous route by the 60th passage but retained its ability to grow in high titer in HKC and in chick embryo cell culture. The titer of this 35–24 line was usually 1 to 1.5 logs higher in cell culture at 24° than at 37°. This line was considered encouraging in respect to qualities essential for a live virus vaccine and manipulations to attempt further attenuation are being carried out.
Delayed Sensitization to Purified Blood Group Substances in the Guinea Pig
Authors: Janković Branislav D. , Waksman Byron H.
Published: January 2023

Guinea pigs sensitized by intradermal or footpad injection of purified blood group substances, in complete adjuvant or in saline, developed typical delayed hypersensitivity to both homologous and heterlogous antigens, as well as humoral antibody more or less specific for the homologous antigen in each case. Some degree of cross-reactivity was observed between the blood group substances and A(H) prepared from hog mucin and pneumococcal S XIV polysaccharide. The delayed reactions observed, on the basis of control studies, appeared to involve the blood group substances themselves rather than contaminant small molecules. Reasons are presented for concluding that specificity was determined by the backbone structure of these molecules rather than their surface configuration.
Studies on Hemolysin Production in Trypan Blue-Treated Rats
Authors: Brown David V. , Norlind Lorna M.
Published: January 2023

It has been shown that the effectiveness of trypan blue in suppressing hemolysin response is related to the size of the dye dose and is dependent on the appropriate sequential administration of dye and antigen. In vivo or in vitro inactivation of antiserum by the dye could not be demonstrated. There was evidence that trypan blue acted primarily on splenic sources of antibody, but that other sites were also affected. Trypan blue treatment regularly produced splenomegaly and the amount of splenic antigen uptake and antibody production were found to be inversely related to the degree of splenic enlargement. The impairment of antibody production was attributed at least in part to the reduction of uptake of particulate antigen in the enlarged spleen. The histologic changes found in the enlarged spleens resembled those described after injection of macromolecular compounds such as polyvinylpyrrolidone and methylcellulose, which also suppress hemolysin response. These observations suggested that the activity of trypan blue might be attributed to its capacity to form macromolecular complexes with serum proteins.
Studies of a Complement-Fixing Antigen from Group A Streptococcal L-Forms
Authors: Crawford York E.
Published: January 2023

In the complement fixation test a streptococcal L-form antigen was shown to react against patient sera in association with streptococcal infection. The per cent of men with L-form reactive sera increased concomitantly with increasing isolations of group A streptococci in the streptococcal epidemics of 2 successive years. The L-form antibody is associated with streptococcal infection, but is not group A specific. It is present in a very high proportion of patients with acute rheumatic fever, but tends to decline in titer during treatment and convalescence. A high degree of qualitative and quantitative correlation exists between the L-from CF antibody titer and the antistreptolysin O titer of naval recruits.
Effect of Antibody Concentration and Temperature upon Physical Adsorption and Histamine Release
Authors: Feigen George A. , Nielsen Christen B. , Terres Geronimo
Published: January 2023

An investigation was made into the nature of passive in vitro sensitization of guinea pig ileum by parallel studies of the effect of temperature on the physical adsorption of antiovalbumin and the magnitude of histamine release following challenge with antigen.

The uptake of radioiodinated rabbit γ-globulin by strips of guinea pig ileum was studied for several concentrations of protein at temperatures ranging from 20° to 37°C. There was no essential difference in the rates of physical adsorption among the several categories tested, the average first order velocity constants being 0.020 and 0.024 min-1 for 20° and 37°C, respectively. Tissues immersed for 60 min in concentrations of antiovalbumin ranging from 0.046 to 0.273 mg/ml at 20°C and 27°C, and from 0.009 to 0.228 mg/ml at 37°C, took up labeled antibody according to a simple function of the bulk phase concentration. The relationship between the bulk phase concentration and the amount physically adsorbed was not affected by temperature. Antibody that had been adsorbed to tissue during the first incubation phase could be eluted by washing with Tyrode's solutions, but the amount eluted was not influenced by temperature. When these tissues were subsequently challenged in the presence of 0.1 mg/ml ovalbumin a constant proportion of label was removed but, as control experiments showed, this was no greater than that which could be achieved by washing with Tyrode's. The release of histamine from tissues of actively immunized animals was increased by elevating the temperature during the challenge step. Variations of temperature during the adsorption step that preceded challenge had no effect upon histamine release if the subsequent challenge temperature was constant. Although the amount of antibody physically adsorbed was influenced only by bulk phase concentration and not by temperature, the quantity of histamine released for a given degree of physical adsorption was greatly increased as the temperature of the adsorption step was elevated, the activation energy of this process being 18 kcal.

Since both physical adsorption and histamine release depend upon the concentration of antibody in the bulk phase, the relationship between these two processes is not a specious one. It is our view that the effect of temperature observed in these studies is to activate receptor sites in such a way as to increase the proportion of histamine-bearing cells which are in a critical state preceding challenge with antigen.
Immunoelectrophoretic Identification of Guinea Pig Anti-Insulin Antibodies
Authors: Yagi Yasuo , Maier Patricia , Pressman David
Published: January 2023

Two anti-insulin antibodies from guinea pig antisera were isolated by chromatography on diethylaminoethyl cellulose (2) and examined by immunoelectrophoresis and by radioautography with the aid of I131-insulin and the rabbit antiserum against guinea pig serum components. Peak I or Peak II antibody fraction showed a single radioactive are in the γ-globulin (I) or in the β2-globulin (II) region, respectively, indicating their difference in the electrophoretic mobility. When the original antisera were used, the resultant radioactive are represented a composite of the two arcs obtained with two isolated antibody fractions. The anode end of the Peak I antibody are coalesced with the middle portion of the Peak II antibody are, thus producing a single long line covering the β2- and γ-globulin regions with a distint spur between these two areas. This line and the spur corresponded exactly with the long strong are (so-called γ-globulin arc) and with the very faint spur observed on the stained slide. The relative intensity of radioactive line in γ- and β2-globulin portions roughly reflected the relative antibody activity in Peak I and Peak II antibody fractions. The method is extremely sensitive for detecting anti-insulin antibodies. Positive results were obtained with antibody concentrations as low as 0.033 to 0.16 µg/ml. In addition, it requires only a few microliters of the sample and the two different antibodies are clearly distinguishable. Two antibodies are different in their reaction with rabbit antiserum against guinea pig serum. Both antibodies have some antigenic determinants in common, but Peak II antibody has some determinants which are not present in Peak I antibody. The complexes prepared by incubating I131-insulin with the antisera migrate significantly faster than the free antibodies.
Photometric Methods for the Measurement of Hemagglutinating Viruses and Antibody
Authors: Drescher Joachim , Hennessy Albert V. , Davenport Fred M.
Published: January 2023

A photometric method for titration of virus using equipment available in this country has been described. The standard deviation of mean titer values found in a series of replicate titrations carried out in one laboratory was 3.5%. The average difference in titer values found in three different laboratories using several strains of virus was 7.87%. Such reproducibility has not previously been achieved and the use of the method may permit development of an international standard for measurement of hemagglutinin.
Photometric Methods for the Measurement of Hemagglutinating Viruses and Antibody
Authors: Drescher Joachim , Davenport Fred M. , Hennessy Albert V.
Published: January 2023

A photometric method for the precise measurement of specific hemagglutinating inhibiting antibodies is described. The average difference of titers obtained in two different laboratories by different technical teams using different instruments was 9.6%. Procedures for the quantitative analysis of mixtures of antisera and of viruses were described and a high degree of accuracy was found when they were employed. The findings suggest many applications, including the possibility of establishing useful international standards of reference.
The Qualitative Receptor Analysis in its Application to Typhoid Fever
Authors: Felix A.
Published: January 2023

One of the unsolved problems of immunology is the question as to what relation the antibacterial immune bodies—agglutinins,precipitins, complement-binding bodies, bacteriolysins and opsonins—bear to each other. Although they have all been known for many years and play a most prominent part in bacteriological practice in daily recurring experiments, in vivo or in vitro, their relation to each other is not yet cleared up. While some scientists regard them as isolated substances, which carry on their activities independently of each other, others refer agglutination, complement fixation, bacteriolysis, etc., to one undivided immune body, which imparts the capacity to the immune serum, to act upon the bacterial antigen in the various forms to which specific names have been given according to their separate reactions. There are weighty arguments, pro and con, for both opinions.

There are now available entirely new points of view in reference to the working out of these problems, since it has been proved by Weil and Felix that in large groups of pathogenic and saprophytic bacteria the antigen is not homogeneous, but consists of two separate parts which differ from each other in principle.
The Protection of Dogs Against Rabies by Umeno's Method of Preventive Inoculation
Authors: Hata S.
Published: January 2023

The results are presented of 104,629 preventive inoculations of dogs against rabies in Tokio and Yokohama and their environs during the period since the adoption of Umeno's prophylactic method. It is shown that only 41 of the inoculated dogs developed rabies, while 1699 of the uninoculated group contracted the disease, notwithstanding the latter group represented only one-third of the total number of dogs in the two prefectures.
Immunological Studies in Tubercolosis
Authors: Petroff S. A.
Published: January 2023

Within the last few years the problem of skin hypersensitiveness has again assumed a prominent part in the field of experimental tuberculosis. There has been no great departure as far as the theory and the method employed in these investigations from that held and employed a decade or so ago; however, teh whole tendency has been to follow the older methods of investigations, only attacking it from a little different angle.

A very careful search of literature reveals only a few papers which deal strictly with the production of skin hypersensitiveness with dead tubercle bacilli. The lack of interest in carrying on such inverstigations was probably due to the authorithative statements appearing from time to time that true tubercullin skin hypersensitiveness could not be set up in a normal animal with anything else but living tubercle bacili.
Observations on the Cross Protective Power of Anti-Pneumococcus Monovalent Sera, Types I, II, and III
Authors: Kolchin Betty S. , Gross Louis
Published: January 2023

In 1922 Cecil and Larsen (1) published a paper dealing with their observations on the results of treating pneumococcus pneumonia with Huntoon's (2) Types I, II and III polyvalent antibody solution2 where they brought out among other things the suggestion that the statistical results indicated that the mortality rate from group IV pneumococcus pneumonia was lowered by such treatment. Similar observations were reported by Conner (3) in the same year.

This result was due either to an accidental fluctuation in the mortality rates of the treated and control cases or to genuine antibody protection against Type IV organisms by an antipneumococcus serum made from the three fixed pneumococcus Types I, II and III. This question of possible cross protection was considered by the Influenza Commission of the Metropolitan Life Insurance Society of great interest and practical importance. This investigation was undertaken by the writers at the suggestion of the Commission.
The Production of Precipitins for Ragweed Pollen
Authors: Parker Julia T.
Published: January 2023

It has been proved beyond question that guinea-pigs can be made hypersensitive to pollen (ragweed or rye) (1, 2, 3, 4). However, because of the failure of all workers to demonstrate precipitins to pollens, certain observers (1, 3, 5, 6) still hold that the specific hypersensitive condition brought about by the injection of pollen into guinea-pigs may not be a true anaphylactic sensitization. Although Alexander (12), in one instance, was able to transfer the hypersensitive condition to rye pollen, passively, he was unable to demonstrate precipitins in the serum of the 4 guinea-pigs tested.

In this paper, we are reporting on the results of the successful production of precipitins for ragweed pollen.

Experimental Method of immunization. We were entirely unsuccessful in demonstrating precipitins in the serum of 2 rabbits injected weekly for a period of over two months with a suspension or a weak alkali extract of giant ragweed pollen.
Studies on the Antibacterial Action of Human Saliva
Authors: Zeldow Bernard J.
Published: January 2023

The cofactor necessary for the activation of a salivary bactericidin active against Lactobacillus acidophilus ATCC 4357 was identified both in vitro and in vivo as thiocyanate. Although iodide in sufficient concentration would also substitute for the cofactor, the amount required was incompatible with the concentration found in saliva.
Interaction of Rickettsiae and Phagocytic Host Cells
Authors: Wisseman Charles L. , Gauld John R. , Wood Jane G.
Published: January 2023

Infection of human subjects with virulent or attenuated (Strain E) Rickettsia prowazekii was followed within 2 weeks by the appearance of antibodies which would enhance phagocytosis of homologous rickettsiae by mouse peritoneal leukocytes. Although an injection of conventional killed epidemic typhus vaccine appeared to cause more rapid appearance of antibodies (by the end of 1 week), the titers attained at this time were low and, on the average, did not increase significantly in later specimens. Serum from all groups also enhanced phagocytosis of R. mooseri but for the most part these antibodies occurred in lower titers than the antibodies involved in the opsonization of R. prowazekii. The cross-reactions observed with the murine typhus antigen tended to be lower relative to the homologous reaction in the group which received the living attenuated (E strain) vaccine than in the other groups studied.
The Neutralization of Animal Viruses
Authors: de St. Groth S. Fazekas , Webster R. G.
Published: January 2023

The quantal assay system of influenza virus multiplying in surviving bits of the allantois is shown to be suited to the quantitative study of neutralization. Complications, such as bias due to the continued presence of serum or to shielding of infectible cells from the action of antibody, are not evident in standard tests.

It is demonstrated that a) the final equilibrium is the same whether approached from the side of virus or antibody excess; b) changes in test volume lead to predictable shifts of equilibrium; c) the effect of noninfective virus particles is compatible only with random reversible combination of antibody molecules with antigenic sites. On this evidence a model of neutralization based on the law of mass action is accepted as working hypothesis.

The assay is not sensitive to minor inhomogeneity of the reagents, and thus not suited to the study of heterogenity either of the virus or of the antibody population.
Stress and Susceptibility to Viral Infections
Authors: Jensen Marcus M. , Rasmussen A. F.
Published: January 2023

The susceptibility of mice to intranasally inoculated vesicular stomatitis virus was significantly altered by daily exposure to 3-hr periods of high intensity sound (123 db). Animals inoculated before and after the first period of stress showed an increase in susceptibility. Adrenalectomized mice inoculated on the 2nd day of stress responded in a like manner. Susceptibility of intact mice inoculated on days subsequent to the first was biphasic. Animals inoculated before stress were more susceptible, whereas those inoculated after were more resistant to the virus than the controls. Daily stress subsequent to the day of inoculation further influenced susceptibility.

The increase in susceptibility was independent of adrenal functions. The refractory phase appeared to be related to adrenal activity.
Spontaneous Canine Hypersensitivity to Ragweed. Characterization of the Serum Factor Transferring Skin, Bronchial and Anaphylactic Sensitivity
Authors: Patterson Roy , Pruzansky Jacob J. , Chang Walter W. Y.
Published: January 2023

Canine antiserum against ragweed pollen antigen occurring spontaneously in dogs is capable of transferring skin, respiratory and anaphylactic sensitivity to normal animals. The active fraction in the serum has been characterized by ammonium sulfate fractionation and zone electrophoresis and probably exists as a β-2A globulin. Canine sensitizing antibody may be compared with similar human antibody. Blood histamine determinations in sensitized, challenged dogs showed correlations with anaphylactic symptoms and with pathologic changes at postmortem examinations. The demonstration that the antibodies of the canine antisera which transfer skin sensitivity, respiratory symptoms and anaphylaxis exist in the same fraction obtained by the physical and chemical methods used for separation of serum components in these experiments provides evidence that the same antibodies mediate all three hypersensitivity reactions, although it has not been proved that the same antibody which results in one reaction mediates all three.
Measles and Poliovirus Antibodies in Commercial Preparations of Human γ-Globulin
Authors: Cabasso V. J. , Kiser K. H. , Clarke F. H. , Stebbins M. R.
Published: January 2023

Twenty-three lots of commercial preparations of human γ-globulin (GG) derived from placental extracts were titrated in HeLa cell cultures for antibodies neutralizing measles virus, with cytopathology serving as an end point indicator. Titers of the various lots ranged between 10-2.70 and 10-3.30/0.1 ml of GG, giving a 4-fold difference between the lowest and highest titer. Repeated titrations of two “low” and two “high” titered lots indicated this difference to be highly significant.

Fifteen of the 23 lots were also titrated for the three types of poliomyelitis antibodies by the metabolism-inhibition test in the presence of monkey kidney cells. Titers ranged between 10-3.91 and 10-4.39/0.25 ml of GG for type I, between 10-4.09 and 10-4.70 for type II, and 10-3.79 and 10-4.39 for type III, which parallels the seroepidemiological pattern of the types of poliomyelitis in the U.S.A. The variation between the highest and lowest poliomyelitis titers obtained was similar to that for measles, being 3-fold for type I and 4-fold for types II and III.

The application of these findings to the eventual establishment of minimum requirements for the release of commercial lots of GG is discussed.
Measurements of Complement by Agglutination of Human Erythrocytes Reacting in Immune-Adherence
Authors: Nishioka Kusuya
Published: January 2023

The number of molecules or particles of antigen and the amount of rabbit antibody giving maximal reactivity of HuC′ or GPC′ in 1.0 ml of reaction mixture containing 2 × 107 human erythrocytes were determined by measurements of IAHA in seven antigen-antibody systems; hen egg albumin, bovine serum albumin, bacteriophage T2, Brucella abortus, Salmonella typhosa, Salmonella enteritidis and sheep erythrocytes. With 5 × 107 Brucella organisms sensitized with 0.314 µg Ab N, fresh human or guinea pig serum showed reactivity in IAHA at a dilution of about 1:4000. The sensitivity of this method exceeds that of assays in immune hemolysis in which the same HuC′ reacted at dilutions of 1:33 to 1:41 and GPC′ at dilutions of 1:181 to 1:235.

Complement in high dilutions of human serum combined with sheep E sensitized with rabbit Ab to induce IAHA, but the C′ in the same reaction mixture was unable to induce immune hemolysis of the cells unless 100 to 200 times more concentrated serum was used. On the other hand, the inhibition of IAHA with EDTA, sodium citrate, formaldehyde or Saldox, supports the view that at least four components of the C′ required for immune hemolysis, are similarly necessary to cause IAHA. After the sequence of reaction of IAHA which is analogous to that of immune hemolysis, intermediate complexes, Brucella-Ab-C′1,4,2 were prepared from both GPC′ and HuC′. The reactivity of fresh guinea pig serum or human serum with these complexes in the presence of EDTA is interpreted to represent the reactivity of one or more components of C′3 of the guinea pig serum or the human serum.
Immunoelectrophoretic Study of Mouse Serum and Urinary Esterases
Authors: Talal N. , Hermann G. , de Vaux St. Cyr C. , Grabar P.
Published: January 2023

Normal mouse serum is separated electrophoretically into seven protein bands and four esterase zones designated ρ, albumin, fast α2 and α2-β1. All but albumin are associated with lipoproteins. These zones correspond on immunoelectrophoretic analysis with six precipitin lines that retain esterase activity after antigen-antibody precipitation: the ρ- and slow lipoproteins, albumin and three α2-globulins. The serum cholinesterase is associated with the α2-β1-lipoprotein and is completely removed by chloroform extraction.

Mouse serum albumin is separated by CM-and DEAE-cellulose column chromatography into two immunologically identical fractions one of which lacks the ability to hydrolyze carboxylic esters. This phenomenon represents and example of the molecular heterogeneity of mouse serum albumin.

Normal mouse urine contains two esterases of α1 and β2 mobility, the latter probably of renal origin. Normal mouse urinary albumin, unlike serum albumin, has no esterase activity.
Antigenic Analysis of Polioviruses Employing the Disk Neutralization Test
Authors: Diwan Arwin R. , Ozaki Yoshikatsu , Fulton Forrest , Benyesh-Melnick Matilda
Published: January 2023

A disk neutralization test is described for measuring intratypic antigenic differences that exist among the polioviruses. Varying dilutions of strain specific antisera are incorporated into the agar overlaid on cell culture monolayers. Paper disks containing uniform amounts of homologous or heterologous virus are then placed on the serum-agar surface. If the test virus is not neutralized, a zone of degeneration develops below the disk. Five strains may be tested against one serum dilution on the monolayer of a single 60-mm Petri dish.

Serum titers were reproducible from test to test within a 2-fold range. Thus, test strains which yielded serum titers within 50% of that yielded with the homologous strain can be regarded as antigenically the same. The smaller the titer relative to the titer with the homologous strain, the greater the antigenic differences between the strains.

Early immune sera obtained in monkeys, rabbits, or guinea pigs were more discriminating in being able to detect differences than late immune sera even though the late sera yielded higher neutralization titers.

The disk antigenic test, like the neutralization kinetic test, is dependent directly on the antigen-antibody reaction and is not affected by the growth rate of the virus and other variables. Comparative tests were carried out on the same strains and both methods yielded essentially the same results.

The disk method was applied epidemiologically to follow Sabin's type 3 and Lederle's type 1 vaccines after multiplication in vaccinated persons. Even though the vaccinated persons or contacts may excrete strains with the properties different from those of the vaccine virus, the disk antigenic tests showed that the new virus particles with the altered properties were progeny of the vaccine viruses.
The Temporal Synthesis and Some Chromatographic and Ultracentrifugal Characteristics of Chicken Antibodies
Authors: Benedict Albert A. , Brown Ronald J. , Hersh R. T.
Published: January 2023

Chicken anti-bovine serum albumin antibodies formed following primary, secondary and tertiary antigenic stimulations were fractionated by diethylaminoethyl cellulose chromatography by elution with phosphate buffers of 0.1 M (A), 0.2 M (B), 0.3 M (C), 0.4 M (D), and 0.4 M + 2 M NaCl (E). As assayed by the passive hemagglutination method, early sera had three chromatographically-distinct macroglobulin antibodies (Fractions C, D and E). Fractions C, D and E each lost agglutinating activity following treatment with mercaptoethanol, and in zone ultracentrifugation each sedimented as macroglobulins. Secondary sera had HA antibody in all five chromatographic fractions, with greatly increased activity in fractions eluted with the lower salt concentrations (Fractions A and B), and lower activities in C, D and E. Fraction A was resistant to mercaptoethanol and sedimented as a 7 S antibody. Fraction B had a mixture of high and low molecular weight antibodies. The chromatographic heterogeneity of the macroglobulins was confirmed by ultracentrifugal analyses. The major faster-sedimenting components were in the 15 S, 19 S and 26 S classes.

The relative concentrations of high and low molecular weight antibodies were followed during primary, secondary and tertiary responses, and the significance of these results is discussed.

Soluble antigen-antibody complexes prepared from primary sera had sedimentation coefficients of 9.5 S and 21.5 S. The 19 S globulin contributed about 60% of protein to antigenprecipitated antibody.
Leukocyte Agglutination in Mice
Authors: Mishell Robert I. , Herzenberg Leonard A. , Herzenberg Leonore A.
Published: January 2023

Development of a method for the detection of H-2 and non-H-2 isoantigens with the leukocyte agglutination reaction is described. Non-H-2 leukocyte agglutinins were induced by sensitization with injections of living spleen and thymus cells, by pregnancy and by skin homografts. Cross reaction of non-H-2 antisera with leukocytes of many inbred mouse strains was observed, indicating that these strains share some of the non-H-2 isoantigens. Selective in vivo absorption was done with one non-H-2 antiserum and a minimum of two separate agglutinating factors was found.
Nonpathogenic Rickettsias Related to the Spotted Fever Group Isolated from Ticks, Dermacentor Variabilis and Dermacentor Andersoni from Eastern Montana
Authors: Bell E. John , Kohls Glen M. , Stoenner Herbert G. , Lackman David B.
Published: January 2023

Forty strains of a rickettsia, referred to as the EM rickettsia, which was avirulent for guinea pigs and which retained this property after serial passage in chick embryos were isolated from Dermacentor variabilis collected in two counties of eastern Montana. The EM rickettsia possessed properties common to agents of the spotted fever group. However, although it appeared to be a variant of Rickettsia rickettsii, it could not be identified with any of the four previously distinguished type strains of this species. The EM rickettsia was also isolated from Dermacentor andersoni collected in one of these localities. EM isolates were compared with an avirulent U strain of R. rickettsii which had been recovered from D. andersoni from the Bitterroot Valley, Montana. They differed primarily in their respective capacities to produce cross-reacting antitoxin against the virulent R strain of R. rickettsii. Guinea pigs injected with 104 doses of EM rickettsias developed high titers of CF antibody but little, if any, antitoxin, against the R strain. In contrast, the U strain produced high titers of both antitoxin and CF antibody for the R strain. Guinea pig hyperimmune serum against the EM rickettsia neutralized toxins of three strains of R. rickettsii representing the R, S, and T types, respectively, but did not neutralize toxins of Rickettsia conori, Rickettsia siberica, or the rickettsia from the tick Amblyomma maculatum. A high rate of infection with EM strains was found in the tick populations examined. This rickettsia was recovered from about 6 to 8% of D. variabilis from each of five localities studied. With one exception all strains isolated in eastern Montana were of the EM type. One isolate which possessed the characteristics of strains carried by the tick Haemaphysalis leporis palustris was isolated from a lot of ten D. variabilis from the eastern Montana area. The T strain commonly isolated from D. variabilis from eastern United States was not encountered in the study area.
Variation in Reactivity of Antigenic Factors of the B Blood Group System of Cattle
Authors: Datta S. P. , Stone W. H.
Published: January 2023

The antigenic factors G and Y2 of cattle erythrocytes show dosage reactions in that homozygous cells gave higher titration or absorption scores than heterozygous cells. Data from absorption experiments suggest that there are quantitative variations of the D′ factor. Some of the differences in reactivity (cross-reactions) may be the result of interaction of the genes controlling red cell antigens.