bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Antitoxin at the Onset of Diphtheria in 425 Patients
Authors: Ipsen Johs.
Published: January 2023

The author has determined the antitoxin-titer of 425 patients with clinical manifest diphtheria faucium. Of these, 287 were unvaccinated, 32 vaccinated once and 106 vaccinated with more than one injection.

In the case of the vaccinated the course of the disease was distinctly milder than that of the unvaccinated, while at the same time the antitoxin titre was much higher for the former than for the latter.

When the unvaccinated are divided into groups according to the severity of the disease, there is only a slight difference in the antitoxin-titers of the groups.

When all the cases are grouped according to the antitoxin-titer there is a scarcely demonstrable difference in the course of the disease for groups with a high titer and those with a low titer, provided that the course is indicated by means of the relative occurrence of complications and deaths in the groups.

When a comparison is made between the distribution of antitoxin-titer among diphtherics and distributions among the rest of the population, there are found to be fewer cases of a titer higher than 0.1 A.U. among the diphtherics.

The material is further treated statistically, the author having found a single quantity as an indicator for the course of the disease for each patient. The average course of each group can then be computed as the mean of the course of the individual cases. This provides greater statistical certainty than an analysis of the percentage of complications.

It was then possible to show a significant dependence between antitoxin-titer and course of disease, although the slope of the regression found was rather flat.

The vaccinated patients had a better course of illness than the unvaccinated who presented the same clinical picture on hospitalization and had the same initial antitoxin-titer.
Observations Upon the Specificity of the Complement Fixation Test for Lymphogranuloma Venereum
Authors: Dulaney Anna Dean , Packer Henry , Smith Mary Margaret , Hannah Walter , Brett Roland , Moore Bliful
Published: January 2023

The Lygranum complement-fixation test affords valuable diagnostic information when sera are titrated, particularly in dilutions of 1:20 and 1:40. Titers of 1:40 and above offer good evidence of infection with the agent of lymphogranuloma venereum. Titers below 1:20 can only be interpreted following examinations of subsequent specimens of serum, employing quantitative procedures. Titers of 1:40 or above were obtained with sera from 56 per cent of patients from a clinic for anogenital lesions and from 97 per cent of patients with a clinical diagnosis of lymphogranuloma venereum. If sera are tested only in dilutions of 1:5 the Lygranum complement-fixation test has limited usefulness. Under such conditions non-specific reactions may occur in apparently healthy individuals, in upper respiratory infections, as well as in the presence of venereal diseases other than lymphogranuloma venereum. While early syphilis may occasionally produce false positive reactions with the Lygranum C. F. antigen, these reactions can usually be screened out by titration studies, in which the 1:40 dilution is considered as the critical titer for diagnosis, or by the more tedious procedure of absorption of sera with Kahn antigen. Our experience has been that when titers of 1:40 or higher are manifested in the Lygranum C. F. test, absorption with Kahn antigen does not remove the reactivity for the Lygranum C. F. antigen, thus providing undisputable evidence that multiple infection is present.
Studies on Botulinum Toxoid, Types A and B
Authors: Nigg Clara , Hottle George A. , Coriell Lewis L. , Rosenwald Arnold S. , Beveridge Gerald W.
Published: January 2023

A medium is described for the production of alum precipitated botulinum toxoids, Types A and B. The production methods are simple and the results uniformly reproducible.

The authors wish to acknowledge the helpful suggestions of Lt. Cmdr. J. A. Lichty, MC, USNR in the preparation of this manuscript. The technical assistance of the following is also acknowledged: T/4 Floyd Miller, T/4 Alfred Saks, T/5 L. Geronimus, 1st Lt. Robert Wiseman, PhM 2/C Anna Funke, and T/4 Vivian Andrews.
A Quantitative Study of the Arthus Phenomenon Induced Passively in the Rabbit
Authors: Fischel Edward E. , Kabat Elvin A.
Published: January 2023

Summary and Conclusions

The relationships between the quantities of anti-egg albumin nitrogen and of egg albumin nitrogen and the intensity of the Arthus phenomenon elicited passively in the skin of rabbits have been studied. Minimal Arthus reactions result regularly from intracutaneous injection of about 25 μg of anti-egg albumin nitrogen and are independent of the route by which antigen is administered. If the antibody is given intravenously one to two milligrams of anti-egg albumin nitrogen are required to yield a positive reaction on subsequent intracutaneous injection of egg albumin at a single site. Injection of antigen at several sites in rabbits passively sensitized by intravenous injection of anti-egg albumin gives reactions of reduced intensity.
Biophysical Studies of Blood Plasma Proteins
Authors: Deutsch H. F. , Alberty R. A. , Gosting L. J. , Williams J. W.
Published: January 2023

Marked differences in antibody-activity are found in human γ1-and γ2-globulin antibody preparations. The hemagglutinins and typhoid “O” agglutinin appear to be γ1-globulins. The β-hemagglutinin of plasma represents a small amount of the high molecular weight portion of the γ1-globulin. The antibody responses of rabbits to human γ1- and γ2-globulins, fibrinogen and albumin as studied by the antigen-dilution technic showed that these essentially electrophoretically pure proteins did not represent distinct immunological entities.
Complement-Fixation Test for Diagnosis of Human Viral Encephalitides
Authors: Casals J.
Published: January 2023

The different steps of the complement-fixation test with encephalitis viruses have been revised and certain considerations derived from the experience gained in this laboratory have been presented.
Isoallergic Encephalomyelitis and Radiculitis in Guinea Pigs After One Injection of Brain and Mycobacteria in Water-in-Oil Emulsion
Authors: Freund Jules , Stern E. R. , Pisani T. M.
Published: January 2023

Rivers, Sprunt and Berry (1) and Rivers and Schwentker (2) induced lesions in the central nervous system (CNS) of the monkey by numerous injections of suspensions and alcoholic extracts of rabbit brain. Ferraro and Jervis (3) confirmed and extended these studies. Morgan (4) produced encephalomyelitis in rhesus monkeys by a few injections of suspensions of brain and spinal cord of monkeys combined with killed tubercle bacilli, paraffin oil and an emulsifying agent. Independently, Kabat, Wolf and Bezer (5) using the same technique obtained almost identical results in monkeys but stated that similar experiments carried out in guinea pigs and white mice were negative. In their study, neurologic symptoms were produced in 2 monkeys after a single injection.

It seemed desirable to ascertain whether this type of encephalomyelitis could be produced in the guinea pig.
Neurologic Manifestations in Laboratory Animals Produced by Organ (Adjuvant) Emulsions
Authors: Kopeloff Lenore M. , Kopeloff Nicholas
Published: January 2023

Although these experimental results are limited by the small number of animals used it would appear that: Neurologic disturbances, characterized chiefly by paralysis of the hind limbs, have been induced in normal guinea pigs by single subcutaneous injections of emulsions of homologous and heterologous brain and heterologous kidney, containing Freund's adjuvants, as well as similar preparations of alcoholic extracts of brain. Testicle emulsions were without effect in normal guinea pigs, but induced hind leg paralysis in 2 guinea pigs which had previously received injections of various organ suspensions.It was also possible to produce this phenomenon in rabbits by repeated injections of adjuvant-emulsions of both rat brain and alcoholic extract of sheep brain in combination with egg-white.
Colorado Tick Fever
Authors: Koprowski Hilary , Cox Herald R.
Published: January 2023

Four strains of Colorado tick fever virus were adapted to dilute brown agouti mice by intracerebral inoculation. Three of the above strains had been adapted previously to hamsters, while one strain was adapted directly from a human blood sample. One of the strains was carried through 50 consecutive mouse brain passages. Virus could be demonstrated in the blood of mice by the first day after inoculation, reaching maximal level on the third day. The concentration of the virus in brain tissue showed gradual rise with maximal level on the fifth day post inoculation. Virus was present in all tissues tested but the greatest concentration was observed in the central nervous system and the lowest in the serum. Mice 8 days of age are fully as susceptible to infection by intraperitoneal route as are 28-day old mice to intracerebral inoculation. Resistance to intraperitoneal inoculations of virus begins to manifest itself in 14-day old mice. Neutralization tests with Colorado tick fever virus and antisera prepared against thirteen different viral and rickettsial agents indicated the immunological individuality of Colorado tick fever virus. Of the various species of animals tested for susceptibility to Colorado tick fever virus, it was shown that hamsters succumb to infection, while cotton rats and opossums circulate the virus in their blood but sheep and rabbits do not. The virus is readily filterable as indicated by the fact that the difference in titers between filtered and unfiltered suspensions of Colorado tick fever virus never exceeded 5–10 LD50, which falls within the limits of experimental error. On the basis of rough estimation the virus has a diameter of 35 to 50 millimicrons. The virus remains viable at room temperature for more than 64 days, but less than 100 days, and remains quite stable when kept in the frozen or lyophilized state.
Changes in Embryonated Eggs Inoculated with Influenza Virus
Authors: Parodi A. S. , Lajmanovich S. , Pennimpede F. , Mittelman N.
Published: January 2023

In experimental work with viruses special attention has been given to their immunological and physicochemical properties. Relatively little study has been made of the interaction between the virus and the host, and this has been limited to pathological changes in the infected tissue. The metabolic changes in the host produced by the presence and reproduction of a virus have not been systematically investigated, and we believe that a knowledge of these changes may be helpful to a better understanding of the virus-host interactions.

Burnet (1, 2) studied the pathological changes produced in the chorioallantoic membrane and embryo of the chick by influenza A virus. We were impressed, however, by the fact that the pH values of the allantoic fluid of chick embryos infected with influenza A virus were always higher than normal. This was so striking that in our routine work we used it as a primary test of infection and discarded all fluids that gave a yellow or light green color with brom-thymol blue.
Nutrition and Resistance to Infection
Authors: Guggenheim K. , Buechler E.
Published: January 2023

The influence of diets, quantitatively or qualitatively deficient in protein, on the bactericidal and phagocytic properties of the peritoneal fluid of rats was studied. The effects of various degrees of quantitative protein deficiency were tested on rats which were kept for 4 weeks on diets containing 18, 9, 6 and 3 per cent casein, respectively. In states of moderate protein deficiency (9 per cent and 6 per cent casein) a marked diminution of the bactericidal power of the peritoneal fluid was demonstrated. In states of severe protein deficiency (3 per cent casein) a significant decrease of phagocytic activity was observed as well. For testing the quality of protein from different sources, diets containing 9 per cent of protein, derived from egg, meat, processed soybean, peanut and maize, were employed. Diets containing 9 per cent egg and meat proteins elicited bactericidal and phagocytic activity roughly equal to that elicited by a diet containing 18 per cent casein; 9 per cent soybean protein had an effect similar to that of 9 per cent casein, and 9 per cent maize protein similar to 3 per cent casein. The results obtained, however, from a diet containing peanut protein were different. Rats, which were fed a diet containing 9 per cent of this protein showed an almost complete breakdown of phagocytic activity, whereas their bactericidal power was similar to that of rats fed a 6 per cent casein diet. It is concluded: It is concluded: a) the humoral defense mechanism appears to be more sensitive to protein deficiency than the cellular defense mechanism; b) different food proteins elicit different bactericidic and phagocytic powers. This quality of promoting antibacterial defense corresponds roughly to the growth promoting quality of the respective proteins.
Production of Anti-Haemophilus Influenzae Type b Rabbit Serum
Authors: Eaton F. D. , Gerwe E. G. , Leonard G. F.
Published: January 2023

Data from a study of six groups, containing two hundred rabbits each, hyperimmunized for the production of anti-Haemophilus influenzae type b rabbit serum, when analyzed, were sufficient to determine the optimum bleeding periods. The rate of rise in potency of individual rabbit bleedings different from pooled large scale production bleedings, and such difference probably was due to individual variation in rabbit response and possibly poor response of animals in the production colony due to necessary production methods. From a practical point of view, it appears advisable to begin production bleedings at the eleventh or twelfth week of immunization.
The Antigen-Antibody Reaction with Type A Botulinal Toxin
Authors: Lamanna Carl , Doak Beatrice W.
Published: January 2023

Crystalline botulinal type A toxin has been found to behave as a complete antigen. It is capable of inducing antibody-formation and a state of supersensitivity. Combination with antibody in the flocculative reaction is in harmony with its large molecular size.

Toxin and toxoid appear capable of forming insoluble complexes with normal sera. Some of the characteristics of the complexes are outlined. The particular importance of the temperature-variable made it necessary to study the precipitin-reaction with a given antiserum at several different temperatures. In the quantitative precipitin-studies the phenomenon was notable in the zone of antigen-excess and at lower temperatures.

In the quantitative precipitin-reaction there exists, in the zones of equivalence and antitoxin-excess, a curvilinear relation between the ratio of antibody to antigen in the precipitates and the quantity of antigen added. (The relation is expressed by the exponential equation x = aby where x = antigen added, y = the ratio, and a and b are constants.) If the ratio is plotted against the log of the quantity of antigen added, a linear relation results. Results with the quantitative precipitin-reaction vary for sera from different animals. With horseserum, inhibition in the antibody-excess zone may be complete, and may even extend to the equivalence-zone.

With both horse- and rabbit-sera inhibition of precipitation was not noticed in the zone of antigen-excess. This finding is discussed.

Flocculation of toxoid (prepared by treatment with formaldehyde at pH 7) with antitoxin was studied. Though quantitative differences existed, in general the qualitative findings were like those with toxin.

In titrations by optimal-proportions, a Lederle ‘modified-globulin’ horse-serum gave an “H” type reaction with toxin and an “R” type reaction with toxoid, an individual rabbit-serum gave “H” type reaction with toxin and a pool of rabbit-sera gave an “R” type reaction with both toxin and toxoid.
Neutralization Tests with Eastern Equine Encephalomyelitis Virus in the Chick Embryo: A Statistical Treatment of the Results by the Probit Method
Authors: Crawley John F.
Published: January 2023

The chick embryo has been successfully employed for the quantitative assay of residual equine encephalomyelitis virus in tests with immune serum. Under the conditions of these experiments maximum neutralization of equine encephalomyelitis virus by antiserum was attained within a few seconds of mixing the virus and the serum. Less neutralization was apparent if the virus-serum mixtures were kept at 4 C prior to inoculation. The amount of neutralization which was apparent was related directly to the susceptibility of the embryo or inversely to the number of virus particles necessary to initiate a lethal infection. The greatest neutralization was shown when 15 day eggs were inoculated by the yolk sac route and the least neutralization when 15 day eggs were inoculated by the chorio-allantoic route. Eleven day eggs inoculated by either route showed intermediate degrees of neutralization.
Studies on Lymphogranuloma Venereum Complement-Fixing Antigens
Authors: Hilleman Maurice R. , Nigg Clara
Published: January 2023

An active complement-fixing fraction was extracted with anesthetic ether from suspensions of yolk-sacs infected with the viruses of lymphogranuloma venereum, meningopneumonitis and mouse pneumonitis. The acetone and alcohol insolubility of the active substance was utilized in the preparation of a highly purified fraction. The purified fraction, inactive in itself, was activated by the addition of optimal amounts of lecithin of either yolk-sac or vegetable origin. The ether soluble antigen in the form of a saline suspension showed no loss of activity when stored at refrigerator temperature for more than 18 months. Chloroform extracts of infected yolk-sac suspensions were similar to the ether extracts in that most of the activity was in the extract. Benzene extracts showed slight activity and petroleum ether extracts were inactive, whereas the suspensions after such extractions showed markedly enhanced activity. Purified antigens and ether-extracted suspensions were group-reactive in complement-fixation with serums of patients infected with viruses of the psittacosis-lymphogranuloma venereum group. The purified ether-extract antigen to which lecithin was added was a highly satisfactory antigen for use in complement-fixation tests for infection with the viruses of this group.
Antibody Studies
Authors: Huntoon F. M.
Published: January 2023

Introduction. Since it was first recognized that certain substances, such as bacteria or their products or certain other poisonous substances of animal and vegetable origin, on their introduction into the animal body, stimulated the formation of neutralizing bodies, which were termed antibodies, there has been constant investigation of the laws governing such neutralizations. Nevertheless, in spite of the enormous amount of work that has been accomplished in this field, the true nature of neither antigen nor antibody has been definitely established.

The present series of papers is concerned with attempts to secure purified solutions of antibody, which would allow direct methods of examination as to their nature and which could be used therapeutically without the introduction of extraneous material, having a dangerous or disagreeable effect.

The purification of antibody, as it has been attempted, may be accomplished by the direct and indirect methods.
A Note on the Claim That Agglutinins Are Lipoidal in Nature
Authors: Krumwiede Charles , Noble W. Carey
Published: January 2023

The claim that agglutinins could be extracted from sera by the use of lipoidal solvents, was called to our attention by the address of Jobling (1) on the relation of lipoids to immunity. This claim was made by Stuber (2), (3) who believed he had demonstrated that he could extract the agglutinins from an immune serum with petroleum ether and that the addition of the extracted substances to normal serum would result in an agglutinating value practically equal to that of the unextracted immune serum. He claimed, also, that the serum of normal animals became strongly agglutinative after the animals had received intravenous injections of such extracted substances.

We have attempted to duplicate the results of Stuber without success. However, we hesitated about presenting our findings, first, because of their negative character and secondly, because of a later article by Stuber (3) on the same subject.
The Relation Between the Absorption of Antibodies and the Isolated Protein Bodies
Authors: Umemura Rokuro
Published: January 2023

Summary and Conclusions

The absorption of antibodies obtained together with the isolated proteins, in harmony with the results of investigations by Th. Madsen, J. Henderson-Smith, and Walbum, depends upon the quantity of proteins associated with them. Thus Kraus, in his experiments on absorption of antibodies in normal serum, showed that the maximum degree was attained in fifty-three hours after subcutaneous injection, while it was reached after intraperitoneal injection in thirty hours. But Walbum differs from Kraus in claiming that it took forty hours after intraperitoneal injection to attain the maximum of absorption. This diversity of results is largely due to the difference in the quantity of proteins contained in the serums which they used; but, when the quantity of proteins contained in the material is the same, the absorption of the normal whole serum is faster than that of the isolated proteins. Thus in the practical application of antibodies, it is useless to try to increase the antibody values by means of sheer concentration, without taking into account the quantity of proteins contained in the preparation, if one is to work for the maximum speed of absorption. Hence, we insist on the use of antibodies completely isolated by means of ammonium sulphate, which are associated with comparatively small quantities of proteins. We may draw the following conclusions: The rate of absorption of antibody depends upon the quantity of proteins associated with it.The quantity of proteins contained being the same, the rate of absorption of antibody associated with isolated protein bodies is slower than that of the whole normal serum.There is no difference in the rate of absorption of the antibodies of each isolated protein.Hence there is an advantage in preferring isolated protein bodies, containing a minimum of protein, in the use of antibodies.
Studies on Acute Respiratory Infections
Authors: Mishulow Lucy
Published: January 2023

Differences in the hemolytic activity of streptococci when grown on blood agar were noted by Schottmuller (1) in 1903. The blood-agar plate was generally employed to determine the hemolytic ability of streptococci until Lyall (2) (1914) advised the use of the tube method as a means of differentiation. Later Smith and Brown (3), using the blood agar plate method, introduced a new nomenclature to indicate the reactions obtained. Brown (4) elaborated these findings and gave detailed descriptions of the characteristics to be observed and advocated a classification based upon such observations. He gave a very complete review of the whole subject.

The superiority of either the plate method or the tube method depends upon the answers to the following questions: (a) Does the plate method bring out all the differential characteristics not shown by the latter method, or is the reverse true? (b) Does each method bring out certain characteristics?
Hereditary Blood Qualities
Authors: Ottenberg Reuben
Published: January 2023

Although the inheritance, according to certain perfectly definite mendelian principles, of group-specific substances in human blood has been known for ten years, the application of this information to medico-legal questions has not yet been made. It is the object of the present paper to present the possibilities of this practical application and to define the instances in which it can be used.

In 1908 while working on the relation of the isoagglutination to blood transfusion, I noticed that the groupings were hereditary and followed Mendel's law and made a brief statement to that effect in an article on the technic of the transfusion tests, read with Epstein before the New York Pathological Society (1). At that time I had examined only five families and was uncertain as to a part of the mechanism of the inheritance. For this reason and because of extraneous interruptions to my work, I postponed further publication.
Hemophilus Pertussis Soluble Antigen and Complement Fixing Antibodies
Authors: Parfentjev I. A. , Virion M. E.
Published: January 2023

We succeeded in performing complement-fixation tests, using sterile filtrate of H. pertussis culture as the antigen. We demonstrated that mild peptic digestion easily destroyed the complement-fixing antibodies in immune rabbit and horse sera without impairing the titer of the antitoxic antibodies. The antigen present in filtrates of H. pertussis culture and responsible for the complement-fixation test was highly resistant to digestion with pepsin in acid medium.
Studies in Cellular Growth
Authors: Maltz Maxwell , Spain David M. , Molomut Norman
Published: January 2023

Acceleration of wound healing by multiple graduated doses (“stimulating”) of antisplenic-tissue-serum (ASTS) is reported for large wounds in guinea pigs. These findings confirm our previous observations of the effect of ASTS in accelerating the healing of wounds of traumatically induced non-infected wounds.
Quantitative Studies in Anaphylaxis
Authors: Coulson E. J. , Stevens Henry , Shimp James H.
Published: January 2023

The anaphylactic sensitivity of guinea pigs sensitized with different doses of ovalbumin was determined by gross anaphylaxis.

The dose required to elicit fatal anaphylactic shock increased with increase of the sensitizing dose when the incubational period was held constant at 21 days.

Under certain conditions the minimal fatal shock-doses may be smaller than the lowest dose that is sufficient to sensitize.
Precipitin-Tests in Plasmodium Lophurae Malaria
Authors: Torrey John C. , Kahn Morton C.
Published: January 2023

Summary and Conclusions

Specific precipitin- and collodion-particle-agglutination tests are described with antigens and sera from ducks infected with Plasmodium lophurae. A method for production of a relatively stable antigen from the plasma of ducks heavily infected with P. lophurae is outlined. Antigen is present in two fractions of the plasma from ducks heavily infected with P. lophurae, but the fraction obtained from the second acid-precipitation (pH 3.2) is more potent and stable than that obtained from the first (pH 5.6 ±). In general, precipitin-formation follows the appearance of parasites in the peripheral blood and thereafter may follow, coincide with, or vary inversely as the parasitemia. In ducks that recover, it appears that precipitins persist in the blood for 1 to 2 weeks and then are no longer measurable. Recovery from infection was always associated with precipitin-formation, but precipitin-formation was not always followed by recovery.
Influence of Mode of Immunization on the Relationship between the Development of Tissue Titers and the Release of Hemolysins in Vitro
Authors: Roberts Sidney , Adams Elijah , White Abraham
Published: January 2023

The capacity of surviving tissues to release hemolysins in vitro has been investigated, using tissues from rats immunized by intravenous or intraperitoneal injection of sheep erythrocytes. In addition, an attempt has been made to correlate the results obtained with the development of hemolysin titers in serum and tissue.

In rats immunized by the administration of a single intravenous dose of antigen, the peak in antibody titer of serum and saline extracts of most tissues occurred within 5 days. At this time, minced splenic tissue from these rats showed a rapid release of hemolysins in vitro. This in vitro phenomenon was inhibited by substitution of a nitrogen atmosphere for the oxygen-carbon dioxide mixture otherwise used. The results obtained by extension of the usual 3-hour incubation period to 12 hours suggested an actual production of antibody in vitro. Lymphoid tissue (mesenteric lymph nodes or thymus) obtained from similar animals appeared inactive under these conditions.

Tissue extracts prepared from rats immunized by periodic intraperitoneal injection of antigen attained maximal hemolysin levels which were in general similar to those observed in tissues from the intravenous group. These titers were apparently maintained throughout the period of antigen injection. Surviving splenic tissue from these animals showed no evidence of antibody production in vitro, whereas lymphoid tissue exhibited a high capacity for the selective release of hemolysins.

The data suggest that lymphoid tissue and spleen may vary in relative importance in the production and release of antibody in vivo, depending on the mode of immunization employed.
The Immunochemistry of Allergens
Authors: Coulson E. J. , Spies Joseph R. , Stevens Henry
Published: January 2023

Evidence is presented to show that the carbohydrate, which is associated with protein in the allergenic fractions, separated from cottonseed, enhances the anaphylactogenic sensitizing capacity of the allergenic protein but does not determine antigenic specificity and does not influence the shocking capacity of the protein.
The Reversal in Vivo by Bal of HgCl2-Inactivated Influenza A Virus in the Chick Embryo
Authors: Pérez J. Enrique , Baralt-Pérez Josefina , Klein Morton
Published: January 2023

A study was made of conditions under which reactivation of HgCl2-inactivated influenza A virus (PR8 strain) would ocur in the chick embryo by the use of aqueous BAL. The following results were obtained: A 10−4 dilution of allantoic fluid virus in broth was completely inactivated by 1:20,000 aqueous HgCl2 after contact for 30 minutes at room temperature (28 C).The virus-Hg complex did not dissociate upon dilution in the allantoic fluid as shown by lack of infectiousness of the fluid for mice and chick embryos after injection of inactivated virus.Aqueous BAL injected via the allantoic route in 1:400 dilution could reactivate the virus when given from 3 to 5 hours before and from 0.25 to 2 hours after the injection of inactivated virus.Following the inoculation of inactivated virus into the allantoic cavity some free unadsorbed virus was demonstrated in the fluid in some experiments. It was therefore not possible to determine whether reactivation resulted from the action of BAL on the adsorbed virus.
The Immunologic Reactivity of Bovine Serum Albumin Labelled with Trace-Amounts of Radioactive Iodine(I131)
Authors: Eisen Herman N. , Keston Albert S.
Published: January 2023

In vitro studies have been carried out with bovine serum albumin which was tagged with radioactive iodine (I131) by direct iodination or by coupling with radioactive p-iodophenyldiazonium chloride. The tagged proteins proved capable of determining relative antibody concentrations in antisera for the native protein. Antisera directed against native bovine serum albumin did not here distinguish a tagged bovine serum albumin preparation from native bovine serum albumin in quantitative precipitin studies.
Studies on Pathogenesis and Immunity in Tularemia
Authors: Downs Cora M. , Woodward John M.
Published: January 2023

Living organisms of certain strains of Bacterium tularense were found to elicit a high degree of immunity in white mice when inoculated in sublethal concentrations. Killed vaccines gave markedly less protection in proportion to the amount of antigen injected than was obtained with living vaccines. Strains of low virulence multiplied following their inoculation into white mice, but decreased progressively after the fourth or fifth day until none could be demonstrated in spleen, liver and heart blood on or about the 15th day. Mice immunized with a number of strains of lowered virulence were highly resistant to infection with virulent strains and disposed of the organisms very rapidly. As few as 20 living cells of the Jap strain produced a good immunity when inoculated into white mice. Vaccination of white mice with living Jap cells produced a high degree of immunity within three days following inoculation. The Jap strain of Bact. tularense provided white mice with an immunity against more than one virulent strain.
Production of Specific Antisera for Enzymes that Decompose the Carbohydrates of Pneumococcus Types III and VIII
Authors: Sickles Grace M. , Shaw Myrtle
Published: January 2023

Antisera were produced in rabbits for the enzymes that decompose pneumococcus Type-III carbohydrate and also those that split pneumococcus Type-VIII polysaccharide. The antisera are as sharply specific as the enzymes; each neutralizes enzymes of homologous type only.

The neutralizing action of the antisera was demonstrated by in vivo as well as in vitro methods.
Production of Specific Pneumococcus Carbohydratesplitting Enzymes in Media to Which the Specific Substrate was not Added
Authors: Shaw Myrtle , Sickles Grace M.
Published: January 2023

Strains of the soil microörganism, Bacillus palustris that produce enzymes active against pneumococcus Type-VIII polysaccharide when grown in a medium containing Type-VIII carbohydrate, produced similar enzymes when grown on beef-extract broth to which no pneumococcus carbohydrate had been added. The enzymes prepared in both media decompose pneumococcus Type-VIII polysaccharide in vitro and protect mice against infection by pneumococcus Type VIII.

Three serologically different enzymes were distinguished.

Strains of Bacillus palustris that in mineral media containing Type-III carbohydrate produce enzymes which decompose pneumococcus Type-III polysaccharide also produce in broth enzymes active on Type-III carbohydrate, but they are of low titer.
Relationships of Proshigella to Other Members of the Enterobacteriaceae
Authors: Carpenter Philip L. , Stuart C. A.
Published: January 2023

Summary and Conclusions

Five strains of Proshigella dispar, one Proshigella sonnei, two Shigella paradysenteriae, and four anaerogenic coliform strains, moderately heterogeneous in their biochemical reactions, could be arranged in an antigenic sequence showing numerous interrelationships. The anaerogenic coliform strains appeared to be intermediate links in the series. It is suggested that these organisms be considered members of the genus Proshigella. Cultures of Paracolobactrum coliforme are described which bear a close serological relationship to Prosh. dispar I. Variation induced in one strain of Para. coliforme and in two strains of Prosh. dispar I yielded forms which had acquired motility and varying ability to produce acid and gas from carbohydrates. Accompanying these changes, the antigenic structure of the organisms was altered by acquisition of common flagellar antigens and by loss and gain of somatic antigens. These changes in one case converted a Prosh. dispar I into a Para. coliforme. The types and subtypes of Prosh. dispar and the anaerogenic coliforms studied do not at present seem sufficiently distinct to warrant species designation. They appear to be steps in an evolutionary series.
The Zone of Localization of Antibodies VIII.
Authors: Eisen Herman N. , Pressman David
Published: January 2023

Absorption of the kidney-localizing antibody from an anti-rat-kidney serum with several fractions of kidney homogenate demonstrated that the kidney-tissue antigen which combines with this antibody in vitro is contained only in the readily sedimentable fraction of the kidney homogenate. This antigen, furthermore, is not extractable from such sediment by saline solutions of even high concentration, or by acetone and ether, and it is remarkably heat stable.

Liver homogenate, likewise, can absorb the kidney-localizing antibody, although to a lesser extent than can kidney homogenate.

Elution of I131 from homogenates of kidney containing in vivo localized radio-iodinated anti-kidney antibody is accomplished with weakly alkaline solutions (about pH 11), but is not achieved with saline solutions or with weakly acidic solutions. The inability of iodide ion, (non-radioactive) to elute I131 shows that the iodine label does not exchange with iodide ion.

The parallel behavior of the kidney-localizing antibody and the nephrotoxic principle of anti-kidney sera indicates the probable identity of these substances. The results obtained, therefore, support the hypothesis that the nephritis produced by anti-kidney sera is associated with the specific interaction of an anti-kidney antibody with an antigen in kidney tissue.
The Effect of Terramycin on the PR8 Strain of Influenza a Virus in Chick Embryos and Mice
Authors: Vinson J. W. , Walsh F. Tracey
Published: January 2023

Terramycin, inoculated in high concentrations into either the yolk sac or the allantoic cavity, was found to inhibit the PR8 infection of the chick embryo when administered 1–3 hours before, or up to 1 hour after, the inoculation of 10 to 100 ID50 of the virus. Partial protection could be obtained against 500, but not against 1000, ID50 of the virus or by delaying therapy for 3, but not for 24, hours. When tested in concentrations comparable to those found in ovo, the antibiotic did not inactivate the virus in vitro. Concentrations of terramycin comparable to those found in ovo neither prevented the living virus from agglutinating RBC nor prevented the RBC from being agglutinated by the virus. Its presence in the hemagglutination system did not alter the titre of the virus. Oral, intravenous, or intranasal administration of terramycin did not influence the course of infection in mice induced by 25–50 LD50 of the PR8 strain.
The Separation of a Protective Antigen from a Toxin-Producing Strain of Hemophilus Pertussis
Authors: Robbins Kenneth C. , Pillemer Louis
Published: January 2023

The serological characteristics of a toxin producing strain of H. pertussis, # 29, are compared with a typical phase I strain, # 18-323. A water extract of strain # 29 organisms, heated at 56 C for 45 minutes, contains a protective antigen against a typical phase I strain, # 18-323, the challenge organism in the mouse protection test. The protective antigen can be partially separated from the heated, non-toxic, water extract by fractionation with methanol-water mixtures under controlled conditions of pH, ionic strength and temperature.
Effects of Purine Derivatives and Analogues on Multiplication of the Vaccinia Virus
Authors: Thompson Randall L. , Price Marian L. , Minton Sherman A. , Elion Gertrude B. , Hitchings George H.
Published: January 2023

2,6-diaminopurine inhibits multiplication of the vaccinia virus in an in vitro system containing chick embryonic tissue. This inhibition is abolished by adenine at an equivalent concentration, and by adenylic and guanylic acids, yeast nucleic acid, diphosphopyridine nucleotide and hypoxanthine at somewhat higher concentrations. Guanine, xanthine and uracil are inactive.

Several halogenated purines appear to be virostatic in the same system, but adenine did not prevent the inhibition of viral growth produced by 2,6,8-trichloropurine.

Three triazolopyrimidines, including 8-azaguanine, failed to prevent multiplication of the virus.

Benzimidazole is inhibitory but the toxicity is not abolished by adenine, guanine or yeast nucleic acid.

Mice inoculated intracerebrally with a neurotropic strain of vaccinia virus (IHD) were not protected by 2,6-diaminopurine, 2,6-dichloro-7-methyl purine or benzimidazole.
Persistence of Antibodies in Human Subjects Injected with Pneumococcal Polysaccharides
Authors: Heidelberger Michael , Dilapi Marie M. , Siegel Morris , Walter Annabel W.
Published: January 2023

Human subjects injected 3, 5 to 6, or 8 years previously with type-specific pneumococcal polysaccharides usually showed measurable and sometimes relatively high antibody levels when their sera were analyzed after the periods indicated. In instances in which an antibody had disappeared or remained only in small quantity, reinjection of the homologous polysaccharide usually caused antibody to reappear or to increase, although rarely to the original maximum. The lowered secondary response does not amount to a “paralysis” of antibody function and does not extend to primary formation of antibodies to polysaccharides not previously injected.
Studies on the Hemagglutinin of Hemophilus Pertussis
Authors: Thiele Elizabeth H.
Published: January 2023

Summary and Conclusions

Hemagglutinin activity can be demonstrated in the early phases of cultivation of Hemophilus pertussis but disappears as the cultures approach maximal density. Previous work has shown that cells from cultures that have reached maximal density have high immunizing potency. Absorption of supernatants from sonically disrupted H. pertussis cell concentrates with chicken red blood cells removes all of the hemagglutinating activity without diminution of toxicity or agglutinogen titer. Supernatants, after complete removal of hemagglutinating activity by absorption on chicken cells, still retain a considerable portion of their protective antigenicity. A spontaneous precipitate that develops in supernatants contains hemagglutinating activity but does not actively immunize mice. Certain properties of the hemagglutinating principle have been described, and the suggestion is made that there may be at least two hemagglutinins. It is concluded that the hemagglutinating substance of H. pertussis cultures is not identical with the toxin, the agglutinogen, or the immunizing antigen.
Agglutinin Nitrogen in Staphylococcus Antisera
Authors: Kahnke M. Jeanne
Published: January 2023

The quantitative determination of antibody nitrogen was applied to staphylococcus antiserum. Test tube agglutinations suggested a low antibody level, but quantitative evidence showed a high level of antibody nitrogen. The homologous strain of Staphylococcus aureus removed a substantial amount of antibody nitrogen; an air-isolated strain of Staphylococcus aureus showed no appreciable cross reactions with the sera.
The Light-Scattering Properties of an Antigenantibody Reaction
Authors: Goldberg Richard J. , Campbell Dan H.
Published: January 2023

The utility of light scattering measurements on protein systems is discussed. Light scattering data for bovine serum albumin and its homologous rabbit antibody are presented. They describe the turbidity of the system as a function of time. It was found that the rate of aggregation of antibody and antigen molecules into large complexes is dependent on the antibody-antigen ratio. The existence of soluble aggregates in the antigen excess region is verified. Evidence is discussed which indicates that all reactions occurring in an antibody-antigen system are bimolecular.
Effects of Gliotoxin and Other Sulfur-Containing Compounds on Tumor Cells in vitro
Authors: Mason John W. , Kidd John G.
Published: January 2023

Gliotoxin in concentrations of 1 μg/ml or more regularly inhibited the subsequent growth of mouse lymphosarcoma cells after contact with them in vitro during a period of 1 hour at 37 C. Desthiogliotoxin, by contrast, had no effect on the tumor cells in concentrations of 800 μg/ml in comparable tests. All of five synthetic compounds having cyclic disulfide components like that of gliotoxin inhibited the tumor cells in concentrations ranging from 5 to 50 μg/ml. In similar tests these compounds and gliotoxin likewise inhibited the growth of mammary carcinoma cells of C3H mice, though in all instances concentrations several times greater than those inhibitory for the lymphosarcoma cells were required.

The inhibitory effect of gliotoxin was abolished when it was mixed before being brought into contact with tumor cells with high concentrations of cysteine, glutathione, or monothioglycerol at pH 7.4. When gliotoxin was allowed to react with the tumor cells first, however, the sulfhydryl compounds applied subsequently in high concentrations did not alter its inhibitory effect, and this was not prevented when the tumor cells were treated with the sulfhydryl compounds beforehand.

Gliotoxin was found to be equally effective against tumor cells under aerobic and partially anaerobic conditions in vitro. BAL, however, was considerably less effective against tumor cells when air was excluded from the mixture.

The findings as a whole indicate that the cyclic disulfide linkage is essential for the effect of gliotoxin on tumor cells in vitro. Their implications are briefly considered.
A Hemolysis Inhibition Test for the Detection of Antibodies to Newcastle Disease Virus
Authors: Kahnke M. Jeanne
Published: January 2023

Within given conditions, the greater the concentration of Newcastle Disease Virus, the greater was the hemolysis produced in chicken red cells, and the greater the amount of immune serum added to the virus, the greater was the inhibition of hemolysis. Based on these findings, a laboratory test for NDV antibodies is presented. The results of the hemolysis inhibition test correlated with a hemagglutination inhibition test.
Effect of X Rays upon Hemolysin Production in the Rat
Authors: Kohn Henry I. , Smyser Mary P.
Published: January 2023

Rats were irradiated once with X rays (250 kvp, LD50 of 725 r) at various times during the week before and the 5 days after an injection of sheep erythrocytes, and the hemolysin titer followed.

Normally, the peak titer occurred 5 to 6 days after antigen injection. Following irradiation, three principal effects were noted. The peak titer was reduced. The attainment of the peak was delayed. The decline in titer after the peak was delayed. No evidence was obtained that irradiation released appreciable and lasting amounts of hemolysin, or accelerated its disappearance.

Exposure at 1 to 3 days before antigen injection was the most effective per unit dose, 175 r causing marked inhibition.

Exposure within several hours of antigen injection was less effective, and the results tended to be more variable than in other experiments.

Exposure at 1 or 2 days after antigen injection required 350 r to produce an inhibition. Although delay in reaching the peak titer was marked, reduction in the peak was not great. As a result, the titers of the irradiated animals were below the controls during the first 10 days, equal to them during days 10 to 14, and above them thereafter.

Exposure to 350 to 600 r on the second to fourth days after antigen injection, when measurable titers were about to appear or had appeared in the plasma, led to inhibition within 24 hours.
The Effects of Cortisone and Acth on Toxins of Rickettsiae and Salmonella Typhosa
Authors: Jackson Elizabeth B. , Smadel Joseph E.
Published: January 2023

A number of the bacterial, rickettsial and viral diseases of man are characterized by severe toxemia. Furthermore, toxins capable of producing obvious lesions in animals, or their death, are obtained from many of the pathogenic microbial agents (1, 2). Recent reports have indicated that increased amounts of adrenal cortical hormones have beneficial effects on the clinical course of several infectious diseases (3–6). Moreover, Lewis and Page (7) have observed that adrenalectomized rats are more resistant to the shocking action of typhoid toxin if they are under treatment with cortisone. With these points in mind, we undertook an investigation of the possible antitoxic action of cortisone and adrenocorticotropic hormone (ACTH) in mice inoculated with lethal amounts of the toxins of rickettsiae of epidemic typhus and of scrub typhus. Subsequently, experiments of a similar nature were conducted with mice inoculated with the toxin of Salmonella typhosa.