bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Immunologic Response in Rabbits Following the Injection of Heat-Killed Pasteurella Avicida by Several Routes and of Sonic Disintegrated P. Avicida Intracutaneously
Authors: Langner Paul H. , Forrester James S. , Langner Fred W.
Published: January 2023

Summary and Conclusions

The intravenous injection of heat-killed Pasteurella avicida gives a better agglutinin-response and protective resistance than either the subcutaneous or intracutaneous route. A comparative study of inoculations given intracutaneously into the back, intracutaneously into the inner aspect of the thigh, subcutaneously into the back and subcutaneously into the inner aspect of the thigh, showed no superiority of any one site or route in ability to produce resistance to the infection following an intraabdominal inoculation of 1,000 lethal doses of P. avicida. The agglutinin-titers were somewhat higher in the animals injected intracutaneously, whether in the back or the thigh, than in the animals injected subcutaneously. Under the conditions of this experiment, the filtrate of live Pasteurella disintegrated by sonic vibration is a poor antigen when injected intracutaneously into the back. No significant difference in sensitization by the various routes of injection was noted in this experiment using P. avicida as an antigen.
Staphylococcal Toxoid Prepared by Peptic Digestion
Authors: Parfentjev I. A. , Clapp Frances L. , Waldschmidt A.
Published: January 2023

Through mild peptic digestion, staphylococcal toxin can be completely detoxified. This detoxified toxin possesses a marked antigenic property for animals and for human beings. Under the conditions described, the digested toxin exhibited no detectable capacity for combining with specific antitoxin. Digested staphylococcal toxoid seems to have less ability to produce reactions in the human being when compared with a formalinized toxoid of equal or less potency.
The Effect of Reducing Agents on the Fourth Component of Complement
Authors: Pillemer L. , Seifter J. , Ecker E. E.
Published: January 2023

Summary and Conclusions

Reducing agents such as HCN, alkali cyanides, sodium bisulfite and thioglycollic acid fail to inactivate the fourth component of serum-complement. This failure of the cyanide and the bisulfite is in agreement with previous observations made on the reactions of reducing agents and aldehydes; these observations having been variously explained by the protective influence of redox structure, rate of reaction, and dissociation effects.

NaCN and KCN in sufficient concentration inactivate the third component.
Reactivation of Neutralized Influenza a Virus by Dilution
Authors: Taylor R. M.
Published: January 2023

Mixtures of immune serum and influenza A virus which are non-infectious for mice can be made lightly infectious merely by dilution.

Reactivation of neutralized virus can be demonstrated with mixtures made either in vivo or in vitro.

Reactivation of neutral serum-virus mixtures is not complete, and approximately 90 per cent of the virus remains permanently neutralized.
Further Studies of the Orientation of Reactive Sites in Thin Films of Streptococcal Antigens
Authors: Chambers L. A. , Bateman J. B. , Calkins H. E.
Published: January 2023

Films of the streptococcal derivatives NPA and P6, when allowed sufficient opportunity for expansion, exhibit significant differences in reactivity of the two film-faces toward homologous and heterologous antisera. When expansion is incomplete the facial differences are largely obliterated.

Variations in the ratios (AB/A), over a wide range of substrate-pH, indicate the presence of at least two types of reactive site which behave independently. Qualitatively, P6 and NPA films exhibit the same properties; therefore nucleic acid appears to contribute nothing to the serological reactivity of the materials which actually enter into the film-structure.
Studies in Contact-Dermatitis
Authors: Grolnick Max
Published: January 2023

Spontaneous flare-ups at the site of application of a single patch-test of krameria, left in contact with the skin for a period of from one to seven days, occurred in 18 subjects on from the 8th to the 21st day following the initial day of application of the excitant. In 19 subjects, in whom from 2 to 5 applications of krameria, made at intervals of one or more weeks, were needed to produce sensitivity, a flare-up at one previously negative site occurred, and in 4 of these subjects, there were flare-ups at two sites. These sites, moreover, remained inactive for from 10 to 43 days prior to their flare-up. This period was referred to as the inactive phase. The flare-up at sites always occurred in the reverse order of applications to those sites with the excitant and was dependent on the concentration of excitant remaining at these areas.

The flare-up could thus occur as a result of a single patchtest contact with an active excitant of contact-dermatitis such as krameria. When more than one application of excitant was needed to induce sensitivity, the appearance of the flare-up seemed to indicate that each successive application of the excitant produced some immunological alteration, and that the sum-total of these stimuli evoked the final state of hypersensitiveness.

The occurrence of the flare-up in a subject is, therefore, to be regarded as an indication of the active sensitization of the subject to the excitant.
Studies on Measles
Authors: Shaffer Morris F. , Rake Geoffrey , Stokes Joseph , O'Neil Gerald C.
Published: January 2023

Simultaneous inoculation of children and monkeys with measles virus of human origin produces in both, after a like incubation period, a syndrome which is similar except in point of severity. The syndrome in the children is that of typical measles; that in the monkeys is what we and others have regarded as typical of measles in this species. An examination of the results obtained in some 80 monkeys receiving in certain instances human and in others egg-derived measles virus, reveals no evidence of any difference in the picture produced by either of the materials. Both appear to be typical of measles in this species. Inoculation of 36 children with active egg-passage virus produced in 4 mild but definite measles, and in 7 others coryza with or without leucopenia and questionable Koplik spots appearing between the 8th and 15th days after inoculation.
Neutralization of Vaccine Virus by Immune Serum
Authors: Bronson L. H. , Parker R. F.
Published: January 2023

Summary and Discussion

Experiments have been performed with a view to gaining information on the protection afforded by immune serum against vaccinal infection of mice, and in order to correlate the protective potency of serum against virus introduced intracerebrally in mice with that introduced intracutaneously in rabbits. It was learned that virus could be titrated satisfactorily by intracerebral inoculation of mice, and that with the strain of virus used the estimates of potency agreed well with those derived from the results of rabbit-inoculation. This was taken to mean that the virulence of this strain of virus for mouse and rabbit was essentially the same. Addition of immune serum to the viral suspensions protected mice from infection. The moderate irregularity of the titration-curve which was found when virus was injected alone was found to be considerably increased, but not to such an extent as to make the use of the “50 per cent point” an invalid one for measuring viral titer. It will be recalled that a similar observation was made when virus was titrated on the rabbit skin in the presence of immune serum, and furthermore that the degree of irregularity of results seemed to be proportional to the concentration of immune serum. The fact that a similar condition obtains in the mouse suggests that it is fundamentally related to the protective activity of immune serum.

It was found that on dilution of the immune serum its protective capacity fell off regularly, as was found to be the case when titrations were made in the rabbit. It seemed, however, that the power of serum to protect the intracerebrally injected mouse from fatal infection was greater than its capacity to protect against the development of a cutaneous lesion. In evaluating this observation it must, of course, be borne in mind that we were not in a position to recognize the development of a minimal lesion in the brain. However, fatal infection of mice, and cutaneous lesions in rabbits, appeared to follow the introduction of equivalent amount of the original viral suspension of this strain. Further speculation must await fuller information.
Quantitative Studies on the Group-Specific Substances in Human Blood and Saliva
Authors: Wiener Alexander S. , Kosofsky Isidore
Published: January 2023

A method is presented for standardizing isoagglutinating sera to be used for estimating the concentration of group-substances in blood and secretions. It is shown that when the maximal dilution of blood or saliva that neutralizes the isoagglutinating serum or serum-dilution is plotted against serum-dilution, the curves for saliva and blood are quite different. This makes it difficult to determine the relative amounts of group-substances in blood and saliva. The cause for the difference in the curves is presumably related to the intrinsic difference in the test-methods for blood and secretions, namely, the absorptive and inhibitive technics, respectively. The experiments described for the standardization of sera were performed with the blood and saliva of a single group-B individual. Anti-B sera from various sources gave quite different findings, so that it was not possible to predict the results merely from the concentration of agglutinins in the serum or serum-dilution. In the absorptive tests the blood of different group-B individuals were found to give equivalent results whether they were secretors or non-secretors. Moreover, the saliva of different group-B secretors, or of the same group-B individual at different times, was found to be relatively constant in its content of group-specific substance. Saliva, accordingly, is a particularly favorable material for use as a basis for standardization of quantitative studies on group-specific substances.
An Experimental Investigation of an Immunologic Mechanism as the Cause of Glomerulonephritis
Authors: Kay Calvin F. , Lucchesi Pascal F. , Rutherford Robert B.
Published: January 2023

A brief analysis was made of the various concepts which have been advanced in explanation of the mechanism by which acute glomerulonephritis develops. Attention was directed especially to the hypothesis that the disease develops as the result of an antigen-antibody reaction, and particularly to the recent concept that the antigen concerned may be the product of an action of the streptococcus or some of its products upon the proteins of the kidney.

Experiments were devised to test the validity of this concept. Antibodies to antigens prepared from human renal tissue were not found by complement-fixation or precipitative methods in sera obtained from 78 patients with scarlet fever. Attempts to demonstrate a circulating antigen in the early stage of scarlet fever by an immunologic reaction with sera obtained at a later period when antibody, if present, would presumably be in excess, were likewise unsuccessful. Reasons are given to show that the negative results obtained, while failing to give support to the concept, cannot be considered to exclude the possibility of such a mechanism.
The Passage of Antipneumococcal Antibodies Into Pleural Exudates in Rabbits—A Comparison of the Penetration of the Pleura by Horse and Rabbit Sera
Authors: Haviland James W. , McManus Joseph F. A.
Published: January 2023

In their report on the superior effectiveness of rabbit antipneumococcal serum in treating pneumococcal pneumonia Horsfall and Goodner (1) suggested that serous membranes might be more permeable to rabbit- than to horse-antibody. The antibody-molecule in horse serum is about 44 mµ in diameter, whereas, the rabbit-serum molecule is only 11 mµ (2). Under certain circumstances, as in long-continued immunization, however, even horse serum may contain smaller antibody-molecules, as was shown recently by Kabat (3). Horsfall and Goodner based their assumption concerning the permeability of the serous membranes not only on these observations but also on a report by Sabin (4) who was unable to demonstrate the passage of horse-serum antibodies from the blood into the empyema-cavities in four patients who had received fairly large quantities of anti-pneumococcal horse serum intravenously. Horsfall and Goodner, on the other hand, stated that they were able to demonstrate the presence of rabbit serum (i.e., antibodies) in the empyema-fluid of two patients who had been treated with rabbit serum.
Studies on the Mechanism of the Action of Sulfanilamide
Authors: Lynch Helen M. , Lockwood John S.
Published: January 2023

Some time ago we reported (1) on the bacteriostatic action of sulfanilamide on hemolytic streptococci in human serum. At that time it was noted that the addition to the serum of small amounts of neopeptone resulted in two effects: 1. There was definite increase in the amount of growth in sulfanilamide-free controls, and 2. there was marked interference with the bacteriostatic effect of sulfanilamide.

We concluded that human serum from defibrinated blood was not a favorable medium for maximal reproductive activity of hemolytic streptococci; that the addition of small amounts of peptone to the serum provided a medium suitable for the active logarithmic multiplication of young streptococci. At the same time, the presence of peptone tended to prevent sulfanilamide from exercising the full effect of which it was capable in peptone-free serum. We were unable to determine whether the growth-stimulating and sulfanilamide-inhibiting effects of peptone were associated or dissociated.
The Effect of Estrone on Antibody-Production
Authors: Von Haam E. , Rosenfeld Irene
Published: January 2023

In a previous communication (1) we reported that high doses of estrone increased the resistance of mice against an infection with pneumococcus. The present experiments were designed to study the nature of this increased resistance by investigating the effect of estrone upon the antibody-production in rabbits immunized with type 1 pneumococcus.

The effect of sex-hormones on antibody-formation has been studied by few investigators. Castration did not influence appreciably the antibody-formation according to the reports of Weyrauch (2) and Glusman (3). Pregnancy, on the other hand, definitely increased the content of natural and acquired antibodies as shown by the investigations of Dresel and Keller (4), Loewenthal (5), Aycock and Kramer (6) and Hudson and coworkers (7). This increase in protective antibodies is highest toward the end of the pregnancy, when the estrogenic hormones reach the highest concentration, and may “reflect the increase in natural resistance to infection during this period” (Perla, 8).
The Influence of Artificial Fever on Mechanisms of Resistance
Authors: Ellingson Harold V. , Clark Paul F.
Published: January 2023

Interest in the therapeutic use of the febrile state was aroused when Wagner von Jauregg (1) reported the improvement in cases of tabes dorsalis and general paresis following artificial infection with malaria, and suggested that the elevation of temperature was responsible for the favorable influence. This observation started a trend of clinical investigation and trial which has led to the widespread acceptance of artificial fever in the treatment of several diseases. The increasing use of this new type of physical therapy has turned attention to the influence of hyperpyrexia on several physiologic and immunologic processes. Physiologic responses to fever have been clearly described, and are covered by the papers of Heymans and Heymans (2), and a review by Bazett (3), and by the later papers of Bischoff, Ullman, Hill, and Long (4), Kissen and Bierman (5), Neymann and Osborne (6), Krusen (7), and Coulter (8).
The Effect of Homologous Antiserum and Complement on the Multiplication of Vaccinia Virus in Roller-Tube Cultures of Blood-Mononuclear Cells
Authors: Florman Alfred L. , Enders John F.
Published: January 2023

The virus of vaccinia may be cultivated for at least 3 weeks in roller-tube cultures of mononuclear cells obtained from the circulating blood of the rabbit. Following inoculation of the virus, the addition of homologous antiserum to this system does not bring about permanent inactivation of the virus. Mixtures of antiserum and virus giving no reaction in the rabbit's skin give rise to an infection of these mononuclear cells. The infection is maintained even if further amounts of antisera are subsequently added to the culture. The addition of 1 or 2 hemolytic units of complement in the form of fresh normal rabbit-serum does not enhance the effectiveness of the antiserum. In cultures of mononuclear cells, the virus does not increase as rapidly nor reach as high a titer as in cultures consisting principally of fibroblasts. In cultures of mononuclear blood-cells, complement and antiserum appeared to be more effective in temporarily suppressing the activity of the virus than in cultures consisting principally of fibroblasts. The possible application of these observatins in vitro to the dissemination of virus through the animal body and to the maintenance of latent infections is discussed.
Further Studies on the Serology of the Pneumococcus Group
Authors: Mørch E.
Published: January 2023

Eighteen pneumococcal types are set up. An account is given of their relations to the types known hitherto. The establishment of these new types entails an extension of Kauffmann, Mørch & Schmith's schema of the capsular antigens of the pneumococci (table 17). An account is given of the sera required for differentiation within the pneumococcal groups (table 18). The mode of their preparation and the determination and control of their capsular titers are mentioned. The significance of new pneumococcal types in respect to therapy, diagnosis and epidemiology is pointed out.
The Permeability of the Gastro-Intestinal Mucosa of Guinea Pigs to Crystalline Egg-Albumin
Authors: Hartley George
Published: January 2023

Summary and Conclusions

All of the young-adult sensitive guinea pigs used in this experiment developed circulating antibodies following the oral administration of crystalline egg-albumin. About 40 per cent of the sensitive guinea pigs that had been maintained on an adequate vitamin-C diet developed signs of anaphylaxis following a subsequent feeding of the same protein. However, about 70 per cent of the scorbutic sensitive guinea pigs developed anaphylaxis following a subsequent feeding of the antigen. There seems to be a direct correlation during the first few weeks after sensitization between the circulating-antibody titer and the degree of anaphylactic shock produced by the oral administration of antigen in scorbutic and non-scorbutic sensitive guinea pigs. After several weeks at a maximal level the circulating antibodies gradually decreased and finally disappeared entirely within two to three months despite the continued weekly feedings of the antigen. However, the antibodies reappeared following a subsequent parenteral injection of antigen in these animals, proving that this phenomenon is not due to a depression of the antibody-forming mechanism. The possibility that this disappearance of circulating antibodies despite the continued feeding of antigen might be due to the localization of the ingested antigen by the antibodies in the gastro-intestinal mucosa, which would prevent the antigen from reaching the general antibody-forming organs, is discussed.
The Agglutination of Intact Azo-Erythrocytes by Antisera Homologous to the Attached Groups
Authors: Pressman David , Campbell Dan H. , Pauling Linus
Published: January 2023

It has been shown that sheep erythrocytes to which azophenylarsonate groups have been attached are agglutinated by anti-azophenylarsonate rabbit serum; the fact that this agglutination occurs when as few as about sixty arsonate groups per cell are present provides evidence that the cells need not be covered by antibody in order for agglutination to take place.

It was also observed that erythrocytes to which ovalbumin has been attached through reaction with bisdiazotized benzidine are agglutinated by anti-ovalbumin serum. Bisdiazotized benzidine itself slowly agglutinates erythrocytes, presumably through the formation of azobiphenylazo linkages between cells.

Azo-erythrocytes with attached azophenylarsonate groups or ovalbumin-molecules can be agglutinated by anti-erythrocyte serum as well as by anti-azophenylarsonate or antiovalbumin serum.
Taxonomy of Salmonella-Like Coliform Organisms
Authors: Saphra Ivan , Silberberg Murray
Published: January 2023

The Salmonella definition propounded by P. Bruce White in 1929 and accepted and published 1934 (1) by the Salmonella Sub-Committee of the Nomenclature Committee of the International Association of Microbiologists, stated that Salmonella organisms form a large genus of serologically related, gram-negative and non-sporing bacilli, which are usually motile; which fail to ferment lactose and sucrose, to clot milk, to liquefy gelatin or to produce indole, which regularly attack glucose either with or without gas production, and all the known species of which are pathogenic for man, animals, or both.

Since that time, serologically typical Salmonella strains have been observed which do not possess all the aforementioned cultural characteristics. On the other hand, cultures belonging to different bacterial species, e.g., E. coli and various Shigella have displayed distinct serological relationship to the Salmonella group (2–4).
On Additional Antigens in the Erythrocytes of Cattle
Authors: Ferguson L. C. , Stormont Clyde , Irwin M. R.
Published: January 2023

Thirty antigens have been detected in the erythrocytes of cattle, by means of iso-immune sera produced by transfusing blood from one individual into another, or by immunizations of rabbits with bovine cells, or by both methods. Each cellular character appears to be produced by a single gene, although some may be products of linked genes. Since these antigens are passed only directly from parent to offspring, these characters may be used for exclusion in cases of disputed parentage in cattle.
The Effect of Body-Temperature Upon Hemolysin-Production in the Rat
Authors: Kopeloff Lenore M. , Stanton Alfred H.
Published: January 2023

The hemolysin-response in rats following a single injection of sheep's red blood corpuscles was found to be influenced by body-temperature. After high section of the spinal cord, rats maintained at an average body-temperature of 5 C below normal showed a markedly diminished hemolysin-response. When the body-temperature was subsequently raised to normal, a sharp rise in titer occurred within 36 hours.
Ascorbic Acid and Immunity
Authors: Spink Wesley W. , Agnew Suzanne , Mickelsen Olaf , Dahl La Meta
Published: January 2023

Synthetic ascorbic acid injected intravenously into human subjects having a deficiency of ascorbic acid in the serum did not result in an in vitro increase in the bactericidal action of whole blood for coagulase-negative staphylococci. Under similar circumstances, the intravenous administration of ascorbic acid was not followed by a rise in the bactericidal titer of serum for E. coli and E. typhosa. The bactericidal action of normal, human serum is not decreased for E. coli, E. typhosa and Shigella paradysenteriae Flexner when the ascorbic acid is completely oxidized in the presence of small amounts of copper.
Tetanus Immunization: Effectiveness of the Stimulating Dose of Toxoid Under Conditions of Infection
Authors: Zuger Bernard , Greenwald Charles K. , Gerber Herman
Published: January 2023

Two groups of 75 guinea pigs each were immunized with two doses of alum precipitated tetanus toxoid one month apart and subsequently infected with tetanue spores. An additional dose of toxoid was given to one of the groups at the time of infection and withheld from the other. In the group which received the extra toxoid there occurred 8 cases of local tetanus and no cases of generalized tetanus as against 13 cases of local tetanus and 4 cases of generalized tetanus in the group which did not receive the extra toxoid. There is also an indication that a larger number of animals with low antitoxic titers at the time of infection will escape without symptoms or slight symptoms if given a smultaneous dose of additional toxoid than if not so treated. A small number of animals were observed for changes in the titers of the circulating blood following infection. Those given additional toxoid showed increases in antitoxic titers by the 5th day after infection as compared to the 8th–10th day in those not given additional toxoid. The results confirm similar observations previously made by us on partially immunized guinea pigs.
The Use of Radioactive Phosphorus As a Tracer in Hemolytic Streptococci
Authors: Ross O. A.
Published: January 2023

Summary and Conclusions

Radioactive phosphorus has been shown to be assimilated, during growth, from an inorganic source by Lancefield Group A hemolytic streptococci. The radioactivity is detectable in an acid precipitate from the supernate and the “M” fraction of the sediment of sound-treated streptococci. The ratio, radioactive to total phosphorus in the media as compared with that in the supernate fraction, was found to be 2.04. The concentrations of radioactive phosphorus tested have no apparent effect on the quantity or type of growth obtained. Likewise, no change in the colonial type of growth was noted.
The Demonstration of Pneumococcal Antigen in Tissues by the Use of Fluorescent Antibody
Authors: Coons Albert H. , Creech Hugh J. , Jones R. Norman , Berliner Ernst
Published: January 2023

The object of this investigation has been to determine the feasibility of using chemically labelled antibodies as reagents for the detection and orientation of antigenic material in mammalian tissue. Such a method requires the retention of specificity by the antibody-molecule during and after the necessary chemical manipulation, a stable chemical linkage between the antibody and its label, and a label that can be detected when present in minute quantities. A further important requirement demands the separation of the labelled-antibody solution from unconjugated tracer-material. In addition a method of this sort would obviously be more useful for many studies if it were possible to determine not only those organs, but those cells which contain the antigen in question. Accordingly we investigated the possibility of employing materials for labelling that could be detected by optical rather than by analytic or radiographic methods.
Cutaneous Reactions to Animal Plasma-Proteins in Man
Authors: Savage George M. , Taylor Henry Longstreet , Keys Ancel
Published: January 2023

Methods of collecting sterile bovine plasma have been developed. These are applicable both to small-scale and to large-scale use. Methods of preparing bovine albumin have been studied. It is shown that methyl-alcohol fractionation maintains sterility better than fractionation by ammonium sulfate. Fractionation by electrophoresis could not be carried out in complete sterility. A survey has been made, involving 8000 skin-tests in 350 men, of the incidence of cutaneous reactions to 8 animal plasmas, to the separated albumin and globulin of bovine plasma, to products of bacterial metabolism in such materials, and to various preservatives. Individuals who react to the plasma-proteins of one animal species do not necessarily react to those of other animal species. Cross-reactions are few. The incidence of positive reactors to bovine albumin is markedly less (2.6 per cent) than to the whole bovine plasma (12 per cent). The severity of the reactions is also less. Pseudoreactions are readily produced by the products of bacterial metabolism in these materials, even when the contamination has been relatively small, the period of incubation short, and the temperature low (5 C). A number of common serum-preservatives produce a high incidence of pseudoreactions. Phenol and methyl-para-sept produce the smallest number of pseudoreactions.
Preparation and Use of Rh Testing Sera
Authors: Gallagher Fred W. , Jones Lloyd R.
Published: January 2023

The existence of an antigen in the erythrocytes of rhesus monkeys, and accordingly designated as Rh, which is found also in the red blood cells of most human beings, was reported in 1940 by Landsteiner and Wiener (1). Methods for preparing anti-Rh sera in experimental animals and of testing for the antigen in erythrocytes are described by these same workers (2). It has been shown, also, that Rh agglutinins may appear in the blood serum of certain individuals who are devoid of the antigen, and that this appearance may be associated with disorders of clinical importance, e.g., transfusion reactions and erythroblastosis fetalis (3, 4). In connection with our study (5) of these problems we have employed antisera from animal and human sources in testing for the Rh antigen. In the present communication are reported our experiences in the production of animal sera and in the absorption of these sera for the purpose of enhancing their usefulness.
Studies on the Toxins of Shigella Dysenteriae (Shiga)
Authors: Olitzki L. , Bendersky J. , Koch P. K.
Published: January 2023

The S-variant of Shigella dysenteriae (Bukarest strain) contains at least 2 toxic substances: a neurotoxin and an enterotoxin. It also contains a non-specific toxic substance found in other gram-negative bacteria. The R-variant contains only the neurotoxin and the non-specific toxic substance. The same toxins are found in washed bacteria as in the filtrates of liquid cultures. The neurotoxin is completely destroyed by heating at 100 C for 30 minutes; the enterotoxin, by heating at 100 C for 2 hours; the non-specific toxins are heat-resistant. From the egg medium of Olitsky and Kligler a fraction, “K”, was separated which, when added to a peptone solution or to synthetic media, favors growth and the appearance of S-variants in R-cultures. All toxins present in the bacterial bodies are demonstrable at approximately the same time in the filtrates of the culture. When the R-S variation takes place, the neurotoxin is demonstrable a week or more before the enterotoxin. On synthetic media the R-variant of both strains tested shows stricter nutritive requirements than the S-variant; it is unable to use glucose in the absence of nicotinic acid or ammonium as source of nitrogen. S-variants are derived from R-strains when large masses are seeded on simple media. R-variants are obtained from S-strains when the latter are grown in the presence of S-antiserum.
Demonstration of the Efficacy of Vaccination Against Influenza Type A by Experimental Infection of Human Beings
Authors: Henle Werner , Henle Gertrude , Stokes Joseph
Published: January 2023

The efficacy of allantoic fluid vaccines in the prevention of experimental human infection with the virus of influenza A has been studied. Of 28 control individuals, 10 came down with clinical influenza following inhalation of a recently isolated active virus. Only 1 case, which had not responded to vaccination, occurred among the 44 vaccinated persons, 27 of which had been immunized 4 months prior to the exposure.

There was good correlation between the pre-inhalation antibody level and the degree of protection in that most of the clinical cases occurred in the group with the lowest antibody titer as measured both by mouse protection and inhibition of red cell agglutination technic. Increase in the antibody level decreased the morbidity.

The clinical picture of the experimental disease confirmed the observation of earlier investigators. Since a number of individuals harbored pathogenic organisms in the upper respiratory tract, all clinical cases were treated with sulfonamides. No complications were encountered.

Subclinical infections were numerous, as shown by slight elevations of temperature, mostly on the second or fourth day after inhalation, leucopenia below 5000, or rises in antibodies 2 weeks following the exposure. These symptoms were independent of each other in that either one alone or any combination of the three could be found. Virus was re-isolated only from clinical cases.

Various questions concerning the subclinical infections are discussed.
Studies on Tetanal Toxin
Authors: Friedemann Ulrich , Hollander Alvin
Published: January 2023

7 tetanal toxins have been bioassayed by 5 methods, namely: 1) Intracerebral injection in rabbits, 2) intracerebral injection in guinea-pigs, 3) intramuscular injection in rabbits, 4) intramuscular injection in guinea-pigs and 5) intramuscular injection in mice. The relative potencies of the 7 toxins were found to be different for each individual method. Conversely, the relative potencies as determined by the five methods were found to be different for each individual toxin. These findings show that toxins from various sources are qualitatively not identical. The lethal dose is determined not only by the number of toxin molecules per ml but also by the toxicity of each individual toxin molecule. Some theoretical implications of these findings are discussed.
The Specificity of Antibodies to Antigens Containing Two Different Determinant Groups
Authors: Haurowitz F. , Schwerin P.
Published: January 2023

Immunization of rabbits with complex antigens containing simultaneously p-azo-phenyl-arsonic and m-azo-phenyl-sulfonic groups furnishes immune sera whose antibodies are precipitated quantitatively by subsequent addition of arsanil-azo-globulin and metanil-azo-globulin. No precipitate was produced by further addition of the homologous arsanil-metanil-azo-globulin. Immunization of rabbits with complex antigens containing simultaneously azo-phenyl-arsonic groups and di-iodo-tyrosin groups gives rise to the production of immune sera whose antibodies are precipitated quantitatively by the subsequent addition of arsanil-azo-protein and iodo-protein. No further precipitate is produced by the addition of the complex arsanil-azo-iodo-protein. An immune serum with the same properties is produced by the injection of a mixture of arsanil-azo-globulin and iodo-globulin into rabbits. Our experiments demonstrate that immunization with a complex antigen AB containing two kinds of determinant groups A and B leads to the formation of antibodies of the type anti-A and anti-B. No indication for the presence of anti-A-B was found. This supports the assumption that antibodies are of a single specificity.
The Relationship of the Protein-Reserves to Antibody-Production
Authors: Cannon Paul R. , Chase William E. , Wissler Robert W.
Published: January 2023

Summary and Conclusions

Rabbits were subjected to diets predominantly deficient in protein in order to ascertain the extent to which depletion of the protein-reserves may influence ability to produce antibacterial agglutinins. No attempt was made to provide a completely adequate intake of vitamins although considerable quantities of several types of vitamins were available in the diet. The purpose, rather, was to determine the effects of severe starvation upon the antibody-forming mechanism. Both young and adult animals were compared with animals of similar age but fed a well-balanced diet. Protein-depletion was determined at intervals before and at the time of antigenic stimulation by the estimation of the total-serum-protein values of the blood. The following conclusions are drawn: Young rabbits made hypoproteinemic by a low-protein diet exhibited a definitely lessened capacity to produce agglutinins when compared with rabbits of similar age but fed a well-balanced diet.Adult rabbits made hypoproteinemic by a low-protein diet or by a lowprotein diet supplemented by plasmapheresis also exhibited a lessened capacity to produce agglutinins as compared with animals of similar age but supplied with an adequate diet.The possible relationship of these findings to conditions of malnutrition associated with severe protein-deficiency and an increased susceptibility to infectious disease is discussed.
Histamine-Protein Complexes: Synthesis and Immunologic Investigation
Authors: Rodney Gertrude , Fell Norbert
Published: January 2023

A synthetic antigen was prepared by coupling the isocyanate derivative of histamine with despeciated horse serum globulin. The immunologic properties of the antigen were studied. The antiserum gave cross-reactions with histamine-azo-proteins, and the precipitative reaction was inhibited by histamine and by β-(5-Imidazolyl) ethyl isocyanate. Protection against symptoms of anaphylaxis in guinea-pigs after immunization with the complex was demonstrated by both in vivo and in vitro experiments.
Studies with H. Pertussis
Authors: Bondi Amedeo , Flosdorf Earl W.
Published: January 2023

A method of separation of the agglutinogen of B. parapterussis from other cellular components is described. This purified agglutinogen has been shown to be free of toxins; it is a protein-like material capable of stimulating the production of antibodies in rabbits. As shown by cross-absorptive tests, this purified fraction has retained the minor antigen common to phase I, H. pertussis. It is probably present as a prosthetic group on the molecule of the major antigen. The comparative chemical properties of the agglutinogen of B. parapertussis and phase I, H. pertussis are discussed. The possible clinical use of the material in skin testing for susceptibility to and immunization against parapertussis is suggested.
Combined Active-Passive Immunization Against Tetanus
Authors: Gold Herman , Bachers Herman
Published: January 2023

The widespread use of active immunization against tetanus has aroused considerable interest in the problem of active-passive immunization against this disease. Physicians wish to know whether it is safe or wise to inject tetanal toxoid when the patient presents himself at the office or dispensary with a wound that requires the injection of 1500 units of antitoxin for prophylaxis against the immediate danger of infection with tetanus bacilli.

The advantages of such a procedure are clear: 1. It cuts down the number of visits required for completion of active immunization. 2. It starts active immunization at the time the patient is very much aware of the need of protection, thus helping to overcome his reluctance. 3. Even if the patient fails to complete the primary course of immunization within the specified 3 months, the injection of the first dose of toxoid will have established the sensitizing mechanism, and the ability to respond to subsequent injections of toxoid that results therefrom, will last a long time (at least 5 years in our experience) and perhaps for life.
Chemotherapy of Lymphocytic Choriomeningitis in Mice and Guineapigs
Authors: Toomey John A. , Takacs William S.
Published: January 2023

Rosenthal et al (1) concluded that the original prontosil of Domagk might prevent or modify the production of lymphocytic choriomeningitis in mice. Because of their experiments and some suggestive clinical evidence, neoprontosil has been used in the treatment of poliomyelitis (2) despite the fact that 1) the original prontosil of Domagk and the neoprontosil sold in this country are not the same drug; 2) the results of experiments with one drug are not necessarily the same as those following the use of another; 3) the results in one species of animals may not be the same as those obtained in another even when the same drug is used; 4) the effects of treatment in one virus disease may have no bearing on the effects that may be produced in another.

Our experiments were performed to determine whether neoprontosil, the American product, or the original prontosil of Domagk would prevent the infection of small animals with virus from lymphocytic choriomeningitis.
Protection against Spotted Fever by Specific Immune Serum Inoculated Intradermally at the Site of Infection
Authors: Anigstein Ludwik , Bader Madero N. , Young Gerald , Neubauer Dorothea
Published: January 2023

The superiority of intracutaneous vaccination against certain infections over the ordinarily used subcutaneous administration of vaccines has been proved repeatedly. This method based on the protective role of the skin although largely neglected in human medicine is known to be successfully used by veterinarians particularly in their fight against anthrax (reviewed by Besredka, 1928) and equine encephalomyelitis (Shoening, Shahan, Osteen and Giltner, 1940). The principle of separate inoculation of virus and immune serum is also advocated in veterinary medicine. Swine are successfully vaccinated against hog-cholera by the virus and immune serum being injected at the same time at different sites and so are cattle against rinderpest. As a whole this method has proven successful although on rare occasions the subcutaneously inoculated immune serum failed to protect the animal. The application of this principle was used in the early immunization of man against yellow fever infection (Sawyer, Kitchen and Lloyd, 1932).
Isolation and Characterization of Influenza Virus B (Lee Strain)
Authors: Sharp D. G. , Taylor A. R. , McLean I. W. , Beard Dorothy , Beard J. W. , Feller A. E. , Dingle John H.
Published: January 2023

A particulate component possessing the biological properties of the influenza virus B (Lee strain), as determined by chicken red blood cell agglutination, precipitation, complement fixation and infectivity for chick embryos, has been isolated in purified preparations from the chorio-allantoic fluid of chick embryos. Concentration and purification were accomplished by adsorption on and elution from chicken red blood cells followed by ultracentrifugation of the eluate at 27,000 g for 1 hour. Electron micrographs of the concentrates revealed circular or ovoid images, measurements of which indicated an average particle diameter of 97.3 mμ. In diagrams of sedimentation-velocity there was present a single slightly diffuse boundary corresponding to a sedimentation-constant of S20° = 832 × 10−13. The probable relation of diffuseness of the boundary to variation in particle size in electron micrographs has been discussed in connection with similar findings with influenza virus A.

The yield of virus from 6,600 ml of chorio-allantoic fluid was 137 mg or 2.1 mg per 100 ml of the fluid. On the basis of nitrogen, the degree of concentration was about 20 times and on volume, practicable for working conditions, 150 times. Preliminary analysis indicated that the virus is a complex containing 21 per cent fat-solvent extractive of which 5.7 per cent are neutral fat, 10.2 per cent phospholipid and 5.1 per cent cholesterol. The non-lipid fraction was 66 per cent of the whole virus and gave the qualitative tests for protein and for desoxy-pentose. It contained 0.44 per cent phosphorus, which, if all was associated with nucleic acid, indicated the possible presence of 3.5 per cent nucleic acid of the desoxypentose type in the whole virus. The total phosphorus of the whole virus was 0.7 per cent. The total carbohydrate of the whole virus was 9 per cent, an amount greatly in excess of that accounted for in nucleic acid. The specific volume determined by pyknometer was 0.865.

A comparison of the characters of the influenza virus B with those found for influenza virus A reveals certain differences between the two agents. The influenza virus A appeared to consist principally of bean- or kidney-shaped particles whereas the particles of influenza virus B were more nearly spherical bodies. An average diameter of 77.6 mμ was obtained from electron micrographs of the influenza virus A, and the sedimentation-constant was S20° = 724 × 10−13. The diameter of the influenza virus A particles calculated from the density and sedimentation-constant, assuming a spherical shape, was 80 mμ. A similar calculation for influenza virus B gave a value of 99.8 mμ, for the particle diameter. The differences in the respective sedimentation-constants and the diameters of influenza viruses A and B, determined from sedimentation-velocity and electron micrographs, were of a magnitude which indicated a significant difference in the sizes of the two agents.
Studies on Complement Fixation with the Viruses of Influenza
Authors: Henle Werner , Henle Gertrude , Groupé Vincent , Chambers Leslie A.
Published: January 2023

The complement-fixing antigens of the viruses of influenza type A and B present in the allantoic fluid of the chick embryo were studied by centrifugation and adsorption. Two fractions of complement-fixing antigen were found, the one sedimentable at 90,000 g and adsorbable onto particulate components of normal tissues and onto chick red cells, the other non-sedimentable at 90,000 g and non-adsorbable. The ratio of concentration of sedimentable to non-sedimentable fraction decreased with time of incubation of the infected embryos.

The 2 fractions either from influenza A or B virus differed in their optimal antibody relationships, in that maximal serum titer for the sedimentable and adsorbable material was approximately 4 times higher than for the non-sedimentable and non-adsorbable fraction.

Absorption of influenza A convalescent serum with the 2 antigenic fractions revealed the presence of 2 serologically distinct antigens in the sedimentable material. One of these, the more active antigen, was identical with the non-sedimentable fraction. In addition, some Forssman antigen was found in the sediment which, however, did not interfere in the reactions.

The activity of the antigen which occurred only in the sedimentable fraction was relatively low and did not account for the difference in optimal serum titers encountered with the sediment or the supernatant fluid as antigens. Other possible explanations for this phenomenon are discussed.
Immunochemical Studies on Human Serum
Authors: Dozois T. F. , Seifter S. , Ecker E. E.
Published: January 2023

Summary and Conclusions

In bacterial complement fixation the inactivation of complement occurs by virtue of the removal of one or more of the C′ components. The bacterial strains employed in these experiments inactivate human complement by fixation of either C′2 or C′3 principally. It is pointed out that these components are also those present in least titer in human complement. “Over-fixation” results in the progressive removal of the other components.

The complement components which are fixed to sensitized V. comma from specifically inactivated complements (siC′), retain their ability to participate in a subsequent bactericidal reaction. Further, the hemolytic functions of the C′ components remaining in the supernate after such a fixation, closely parallel the bactericidal functions of the fixed C′ components.
Influence of Age on the Susceptibility of Mice to Infection with Certain Neurotropic Viruses
Authors: Lennette Edwin H. , Koprowski Hilary
Published: January 2023

Summary and Conclusions

The influence of age on the susceptibility of mice to infection with the viruses of pseudorabies, Bwamba fever, herpes simplex, St. Louis encephalitis, West Nile disease, Japanese B encephalitis, and Eastern, Western, and Venezuelan equine encephalomyelitis was investigated. Susceptibility to fatal infection with any of these viruses by the cerebral route was not found to diminish.significantly with increasing age. Mice as young as 3 days of age were refractory to peripheral inoculation of the SP strain of pseudorabies virus; this, however, may have been due to the low virulence shown by this strain on cerebral inoculation. With the exception of the Venezuelan equine encephalomyelitis virus, susceptibility to extraneural inoculation of the other viruses was found to decrease with increasing age of the animal. The age at which resistance first appeared depended on the virus. Susceptibility to extraneural inoculation of the Venezuelan equine virus was not influenced by increasing age of the animal. Mice of all the ages tested (from 3 to 233 days) were about as susceptible to extraneural as to cerebral inoculation of the virus. It is concluded that resistance to peripheral inoculation of a virus is not wholly a function of age but is dependent to a variable extent upon the pathogenetic properties of the virus.