bluuebunny/crossref_metadata_2025 huggingface dataset:
The Isolation of Influenza A Virus by the Intraallantoic Inoculation of Chick Embryos with Untreated Throat-Washings
Authors: Rickard E. R. , Thigpen Minnie , Crowley James H.
Published: January 2023

A total of 75 untreated and unfiltered nasopharyngeal washings from normal individuals, from patients ill with sporadic febrile upper respiratory disease, and from patients ill during epidemics of influenza were inoculated into the allantois of chick embryos. Repeated passage by the allantoic route demonstrated that chick embryos were little affected by gross bacterial contamination with organisms from the nasopharynges of these patients. Influenza A virus in throat-washings was found to grow readily in the bacterially contaminated embryos. The red blood cell agglutination-phenomenon was used as an indicator of the presence of virus.

In a current epidemic, influenza A virus was isolated and identified in nine out of 20 throat-washings taken at random and examined by the technic described above. Four of the 20 washings produced agglutination on primary egg inoculation. One of these four strains was identified as influenza A virus within 48 hours after the first cases in the epidemic were observed. Human sera of known titer for standard strains of influenza A and B virus were used for the identification of all the strains isolated.
The Chemoprophylactic and Therapeutic Action of a Wide Variety of Chemical Compounds on Two Neurotropic Virus Infections in Mice
Authors: Kramer S. D. , Geer H. A. , Szobel D. A.
Published: January 2023

This report gives the results of 412 experiments testing the prophylactic and therapeutic value of 190 chemical compounds on poliomyelitis and St. Louis encephalitis infections in white Swiss mice. This study was initiated in 1939 and is part of a long range effort to test systematically the usefulness of a wide variety of compounds, both old and new, in preventing or in modifying the outcome of certain experimental virus infections.

In view of our special interest in poliomyelitis, two neurotropic viruses were selected to serve as test experimental infections. One was the mouse-adapted Armstrong Lansing strain of poliomyelitis, and the other was the Webster strain of mouse-adapted St. Louis encephalitis virus. The chemical compounds were supplied to us by a cooperating group of manufacturing concerns.2

Among the 190 compounds tested we found none which possessed any significant prophylactic or therapeutic action on the two test experimental infections.
In Vitro Anaphylactic Response to Polyhaptenic and Monohaptenic Simple Antigens
Authors: Campbell Dan H. , McCasland Gifford E.
Published: January 2023

The foregoing experiments confirm the observations of Landsteiner and van der Scheer, who showed that simple polyhaptenic antigens will produce anaphylactic responses in sensitized smooth-muscle strips. These reactions can be inhibited by the previous addition of univalent haptens and the inhibiting action is not removed by washing the tissue. One of the univalent haptens having a relatively large molecular size produced weak and delayed anaphylactic responses, although it gave no precipitation with homologous antiserum.
Studies in Anaphylaxis
Authors: Smith Maurice I.
Published: January 2023

Summary and Conclusions

Guinea-pigs and rabbits sensitized to ox serum or horse serum, and treated subcutaneously with moderate doses of quinine preceding the reinjection of the specific antigen, have their susceptibility increased from 3 to 10 times to the specific protein, as compared with control sensitized animals.

No appreciable degree of proteolysis could be demonstrated to occur in vitro by treating sensitized serum with the specific antigen, whether incubated alone or with quinine. The augmented susceptibility of sensitized animals to the specific protein when under the influence of quinine cannot, therefore, be referred to the well known action of this drug on ferments.

Quinine added to Ringer-Locke solution perfused through the pulmonary vessels of sensitized or normal rabbits does not cause any noticeable constriction of these vessels. Specific foreign protein added to Ringer-Locke solution perfused through the pulmonary vessels of sensitized rabbits produces pulmonary obstruction to a marked degree. The altered susceptibility of sensitized animals to the foreign protein produced by quinine cannot be referred to any synnergy between quinine and the anaphylactic process on the pulmonary circulation.

It has been suggested that histamine might be the causative factor of anaphylactic shock. On closer investigation it does not appear that histamine is identical with the anaphylactic process, for the following reasons: Histamine does not produce in animals the temperature reactions observed in anaphylaxis.Histamine does not alter the coagulability of the blood, as is noted in anaphylactic shock.Quinine alters markedly the course of the anaphylactic reaction, by augmenting the susceptibility of sensitized animals to the foreign protein; it has no harmful effect on the course of intoxication with histamine.There is no relation between histamine and antianaphylaxis. Neither does desensitization influence the toxicity of histamine, nor does the preliminary treatment with histamine alter the lethal dose of the specific foreign protein in sensitized animals.

A synnergetic relation is shown to exist between histamine and the specific foreign protein in sensitized guinea-pigs. This is probably best explained on the assumption that some points of attack of histamine and of the anaphylactic process are identical.
Antigenic Variation in Clones of Paramecium Aurelia
Authors: Harrison James A. , Fowler Elizabeth H.
Published: January 2023

Antigenic variation in clones of Paramecium aurelia was studied in 61 combinations of 27 different clones and 24 different antisera. It was found that serum-insensitive variants in serum-sensitive clones could give rise to clones of greater, lesser or the same sensitivity of the original parent clone. One new clone of greater serum-sensitivity than its original parent clone was established by continued selection of serum-sensitive individual paramecia in successive clones. This clone showed from time to time some variation in sensitivity to antiserum for its original parent clone but was found to be usually of higher, and never lower, sensitivity than the parent clone in tests done over a period of one year. Nine serum-insensitive clones were derived by continued selection of insensitive members from 7 different parent clones. Two of these regained full sensitivity to antiserum for their original parent clones in 3 months; 2 remained serum-insensitive for a period of 9 months, but reverted to almost the full sensitivity of the original parent clone toward the close of the 13-month period of examination; 5 remained serum-insensitive throughout the periods of their examination which lasted from 15 to 17 months. A single clone grown in antiserum of less than lethal concentration failed to show much variation in sensitivity to the serum. These results are discussed in relation to morphologic phenomena involving nuclear change in paramecia and in relation to the occurrence of antigenic variants in pure cultures of flagellated bacteria.
Studies on the Hemolytic Streptococcus
Authors: Menten Maud L. , Finlay Harold H. , Andersch Marie A.
Published: January 2023

Comparison of toxoid and toxin as an antigen in immunization against scarlet fever warrants the conclusion that the former gives equally good, if not better, results with less local and systemic reactions. This is especially true in younger children. Because of variable degree of refractoriness to immunizing injections among positive reactors it is recommended that readily immunizable individuals be eliminated following three comparatively small doses of antigen by a Dick retest and that further immunization procedures be continued with the remaining positive reactors of the more refractory group.
Serological Reactions of Two Bacterial Levans
Authors: Hehre Edward J. , Genghof Dorothy S. , Neill James M.
Published: January 2023

The levan polysaccharides synthesized from sucrose by a spore-forming bacillus of plant origin and by a strain of Streptococcus salivarius were proved to be serologically reactive and serologically similar substances. The levans gave both precipitation and complement fixation with antiserums produced by immunization with either the streptococcus or the bacillus which had been grown in media containing sucrose, and also reacted with some samples but not with most type 20 antipneumococcus serums.

The carbohydrate in the culture medium was an important factor. The serologically reactive levans were produced in abundant amount in broth containing sucrose or raffinose whereas none could be found in cultures grown with 8 other sugars. Similarly, antiserums reactive with the levans were readily produced by immunization with suspensions of either the bacillus or streptococcus which had been grown in sucrose media but not by immunization with the same bacteria grown in glucose media.
Application of a Quantitative Complement-Fixation Test to the Serum Diagnosis of Typhus Fever
Authors: Varley Florence M. , Weedon Frederick R.
Published: January 2023

A rickettsial antigen with its homologous antibody and complement has been found to give the same straight line relationships described by Wadsworth, Maltaner and Maltaner and Rice for other systems. Charts for aid in practical use are presented. Preliminary tests indicate that the amount of complement rendered inactive by antigen-antibody is not influenced by lytic or slightly anticomplementary properties of the normal sera used for diluting the antiserum being tested.
Experimental Studies on the Yellow Fever Protection Test
Authors: Smithburn K. C.
Published: January 2023

A considerable amount of experimental work has been done on the yellow fever protection test, as result of which we have adopted for use in Uganda an intraperitoneal technic which employs 1 per cent mouse passage virus. The method enables tests to be done with as little as 0.5 ml of serum. It is more sensitive for the detection of antibody in low titer than the standard intraperitoneal method and appears to be no less specific than the latter.
Spontaneous Loss of Specificity of Absorbed Immune Hemagglutinating Sera
Authors: Boyd William C. , Boyd Lyle G. , Warshaver Estelle R.
Published: January 2023

Sterile absorbed immune hemagglutinating sera stored, with or without preservative, in the icebox sometimes develop non-specific agglutinating activity which may occasionally be strong enough to lessen their value as diagnostic reagents. This non-specific activity can be removed by reabsorption.
p-Aminobenzoic Acid Synthesis by Neisseria Gonorrhoeae in Relation to Clinical and Cultural Sulfonamide Resistance
Authors: Landy Maurice , Gerstung Ruth B.
Published: January 2023

With some exceptions, individuals promptly cured of gonorrhea by sulfonamide therapy yielded sulfonamide-sensitive gonococcus cultures with low PAB synthesis, while clinically resistant individuals yielded sulfonamide-resistant cultures with relatively high PAB synthesis. On the basis of this and other evidence presented, it is clear that increased PAB production by gonococci is usually associated with clinical resistance and resistance in vitro to sulfonamides, but is insufficient to account entirely for such resistance.
An Electrophoretic Study of an Anti-Influenzal Horse Serum
Authors: Wyckoff Ralph W. G. , Rhian Morris
Published: January 2023

Electrophoretic analyses and agglutination-inhibition titrations of a hyper-immune horse serum and its fractions indicate that the influenzal antibody in it is associated with the gamma component.
Serologic Studies in Typhus-Vaccinated Individuals
Authors: Zarafonetis C. J.
Published: January 2023

In a preceding communication (1) it was pointed out that certain factors had to be evaluated before the serologic diagnosis of typhus fever in vaccinated individuals could be made with assurance. Among the factors mentioned was the possibility of an anamnestic reaction or non-specific rise in Weil-Felix and/or complement-fixing antibodies due to non-typhus fevers. Numerous papers have been published concerning the appearance of Weil-Felix antibodies in diseases other than typhus in non-vaccinated individuals, but no study has yet appeared regarding similar findings in typhus-vaccinated persons. Complement-fixation in the rickettsial diseases has only recently become generally employed, but in the studies so far reported there have been described no instances of non-specific findings in properly controlled tests.

The present study was undertaken in an attempt to determine what effects, if any, non-typhus fevers might have upon these antibodies in vaccinated individuals. Herein are described the serologic findings obtained in 104 acutely febrile patients who had been previously vaccinated with Cox-type epidemic typhus vaccine.
Weil-Felix and Typhus Complement-Fixation Tests in Relapsing Fever, with Special Reference to B. Proteus OX-K Agglutination
Authors: Zarafonetis C. J. D. , Ingraham H. S. , Berry J. F.
Published: January 2023

During the past two years, Weil-Felix agglutination tests and the typhus complement-fixation tests with purified rickettsial antigens have been used extensively in this laboratory in the serologic diagnosis of typhus fever. The complement-fixation test has been of great value because of its ability to differentiate between epidemic and murine typhus in non-vaccinated cases (1, 2, 3). Thus, in addition to its value to the clinician, the complement-fixation test has obvious significance to the epidemiologist. In fact, typhus surveys in Morocco, Egypt, Greece, Yugoslavia, Italy, Germany, Arabia, and other countries have been greatly aided by this test (4). In these studies, the complement-fixation test has maintained its specificity, and no false-positive reactions have been encountered (3). However, in view of the fact that epidemic typhus fever and relapsing fever epidemics repeatedly occur simultaneously, it was felt that it would be of value to extend these typhus tests to sera from cases of relapsing fever and to note whether or not false-positive or other interfering reactions occurred.
Quantitative Studies on the Neutralization of Pathogenic Agents in Tissues by Circulating Antibodies
Authors: Friedemann Ulrich , Hollander Alvin , Traub Frederick B. , Langstadt Dorett
Published: January 2023

Summary and Conclusions

The investigations reported in the present paper are part of the more general problem of studying immunity reactions with the aid of the methods of the direct and indirect test or, more specifically, by determining the Ai, Ad and Ai/Ad values. These terms have been defined and discussed in the first part of the paper. In particular, the present communication is concerned with the experimental analysis of previously reported observations. It had been found that the intracerebral or rather intraventricular Ai values were very different for individual tetanal toxins and thus revealed hitherto unknown qualitative differences between the toxins. In the present paper, it has been shown that similar differences exist between the intramuscular Ai values of tetanal toxins. On the basis of considerations which have been discussed in the first part of the paper and need not be repeated, the assumption was tentatively made that the differences in the Ai values might be due to differences in the rapidity with which toxins either enter the nerve endings or else are neutralized by antitoxin at the site of injection. In other words, the differences in the Ai values were explained by differences in the relative avidities of the toxins for nerve tissue and antitoxin.

The validity of this explanation was tested by experiments in which the antitoxin was injected at various intervals after the toxin. It was found that an interval of 3 hours between the injection of toxin and the subsequent injection of antitoxin increased the antitoxin requirements 16 times for toxin 64 (Ai = 0.0031 ml) and 260 times for toxin 641B (Ai = 0.2 ml). This result shows that after a certain lapse of time the toxin with the high Ai value is more difficult to dislodge from the tissue than the toxin with the low Ai value. This observation can hardly be explained otherwise than by assumming that toxins with a high Ai value have either a greater affinity for nerve tissue or a lower avidity for antitoxin. After eliminating differences in the Lf values of the individual toxins, the avidities of the toxins for antitoxin were determined by measuring the velocity of flocculation in the Ramon test. These “reduced” flocculation rates were very similar for 5 tetanal toxins. Moreover, the small differences were in no way related to the Ai values. It follows that the differences in the Ai values of tetanal toxins cannot be explained by differences in their avidities for antitoxin. In connection with the above described experiments, this result leaves only the alternative that the differences in the Ai values of the toxins are due to differences in the avidities for nerve tissues.
The Relationship of the Protein-Reserves to Antibody-Production
Authors: Wissler Robert W. , Woolridge Robert L. , Steffee C. Harold , Cannon Paul R.
Published: January 2023

Summary and Conclusions

The ability of protein-deficient adult white rats to fabricate anti-sheep cell hemolysin was compared with that of similar animals which had been supplied with high-quality dietary protein or a protein derivative (Amigen) for a few days prior to injection of antigen. The purpose of the experiments was to accomplish repletion of the depleted protein stores in order to enhance the capacity of the antibody-producing cells to synthesize antibody globulin. Hemolysin titers were determined at intervals after injection of antigen and were compared with those obtained in well-nourished control animals simultaneously injected with antigen. The results were as follows: Protein-repletion of protein-depleted rats by the feeding of high-quality protein, or a hydrolysate of a high quality protein led to a markedly increased output of hemolysin, evident as early as after two days of repletion and pronounced within seven days.The antibody-producing mechanism of rats is not permanently damaged even after feeding a low-protein ration for 191 days, and may be restored to nearly normal levels by the ingestion of adequate amounts of high-quality protein.Protein-repletion of protein-depleted rats may give a temporary increase in the rate of protein anabolism, even exceeding the normal rate in rats which have never undergone depletion.The daily ingestion of 5 mg of ascorbic acid by hypoproteinemic rats exerted no effect upon the output of hemolysin. Experiments are in progress to determine the effect of other vitamins upon production of antibody.
The Preparation of a Potent Toxin of Shigella Dysenteriae (Shiga) on a Semi Synthetic Medium and its Use for the Preparation of an Alum-Precipitated Toxoid
Authors: Olitzki Leo , Bichowsky Leah
Published: January 2023

Shiga toxoid was prepared from cultures of S. dysenteriae on a semi-synthetic medium. Small quantities of this toxoid adsorbed on alum, concentrated, and injected subcutaneously immunized rabbits against multiple lethal doses of toxin.
Studies on the Reversibility of the Antigen-Antibody Reaction
Authors: Morris Marion C. , Karr Helen V.
Published: January 2023

Type III pneumococci sensitized with homologous rabbit antiserum show decreased capsular swelling upon exposure to homologous polysaccharide. This reversal of capsular swelling is type-specific. Following the loss of capsular swelling, the washed suspensions may exhibit swelling again upon exposure to homologous but not to heterologous antiserum. Treatment of sensitized type III pneumococci with type III carbohydrate leads to an increase in mouse-infectivity. The mechanism of these reactions is discussed.
Studies of the Complement-Fixation Reaction in Virus Systems
Authors: Rice Christine E.
Published: January 2023

From these studies of vaccinial systems a short quantitative method of titrating the complement-fixing capacity of vaccinial sera and antigens has been derived. The method is based on that developed in this laboratory (5) for the routine complement-fixation test for syphilis, and involves the use of tables of conversion factors for the determination of the amount of complement needed for 50-per-cent hemolysis under various conditions. The test has been useful in differentiating reactions of sera with several different antigens and of antigens with different sera.
A Heterologous Principle in Human Cancerous Liver: Its Effect Upon the Brown-Pearce Tumor
Authors: Penn H. S. , Jacobsen Elly M.
Published: January 2023

A method for obtaining a heterologous acetone-soluble fraction from human cancerous tissue is described.

This fraction coupled with a protein was employed to obtain an antiserum by injection into rabbits.

Both the acetone-soluble fraction and its antiserum were subjected to experimental procedure by injection into rabbits previously inoculated intraocularly with Brown-Pearce carcinoma.

Two types of controls, both with intraocular implants, were used: (1) noninjected animals and (2) animals injected with normal antigen obtained from human non-cancerous tissue and with normal rabbit serum.

The tumor growth was not modified by injection with normal rabbit serum and acetone-soluble, protein-coupled fraction obtained from human non-cancerous tissue.

Inhibition of tumor growth was demonstrable in those animals inoculated with a rapidly growing Brown-Pearce tumor and injected with a heterologous acetone-soluble lipoid fraction obtained from human cancerous tissue and with its antiserum.
Quantitative Studies on the Neutralization of Pathogenic Agents in Tissues by Circulating Antibodies
Authors: Friedemann Ulrich , Traub Frederick B. , Langstadt Dorett
Published: January 2023

The effect of substances augmenting capillary permeability, on the in vivo reactions between toxins and antitoxins, has been studied. The capillary effect can be demonstrated by the indirect intracutaneous test with diphtheric toxin and the indirect intramuscular test with tetanal toxin. It cannot be demonstrated by the indirect intramuscular test with diphtheric toxin. These findings have been explained on the basis of the nerve carriage theory of Meyer and Ransom. Nutrient broth, Difco peptone, Savita broth without peptone, histamine, the blood group substances, saliva, testicular extract and leech extract were shown to have a strong capillary effect. It is undecided whether or not the capillary effect of the blood group substances is due to impurities. The capillary factor in testicular extract is distinct from the spreading factor. Most substances affecting capillary permeability increase capillary permeability to such an extent that the concentrations of antitoxin in blood plasma and tissue fluid become identical. The indirect test provides a convenient method for studying the effects of substances affecting capillary permeability quantitatively. Some practical implications of our findings are discussed.
Specific Complement-Fixing Diagnostic Antigens for Neurotropic Viral Diseases
Authors: DeBoer Carl J. , Cox Herald R.
Published: January 2023

Summary and Conclusions

A method has been described for the preparation of complement-fixing antigens for eastern and western equine encephalomyelitis and St. Louis and Japanese B encephalitis viruses. Extraction of the antigens in the lyophilized state with benzene, toluene or dichlor-ethylene, renders them specific without producing any appreciable adverse effect upon the antigenicity. The antigens are specific in that they fix complement only in the presence of their homologous immune sera and do not give rise to false positive reactions with human syphilitic or malarial sera when the method of Kolmer and Boerner is employed. The antigens so prepared are quite stable and non-infectious. The method of preparation is a simple one and apparently can be used for the preparation of antigens from various tissues shown to be rich in either viruses or rickettsiae.
Effect of Tris(Beta-Chloroethyl)Amine on Antibody-Production in Goats
Authors: Philips Frederick S. , Hopkins Frances H. , Freeman Marion L. H.
Published: January 2023

The serum antibody-content of goats which had been actively immunized against ricin was allowed to decline by cessation of antigen administration. When serum antibody had reached negative levels of activity, the injection of a single stimulating dose of ricin caused a prompt increase in circulating antibodies such that within one week levels were obtained equal to or greater than previous maxima. However, if immune goats with negative antibody-levels were injected with chronic, leucopenic doses of the nitrogen mustard, tris(beta-chloroethyl)amine, before the administration of the stimulating dose of ricin, anamnestic responses were delayed in all animals and in a few actually decreased by comparison with the responses of controls.

The fact that prior treatment with amine mustard influenced the course of anamnesis was discussed in relation to the untoward effect of the treatment on leucopoietic tissues. It was considered reasonable to attribute untoward change in anamnestic response to a direct toxic action of the agent on leucopoietic tissues which was not mediated by primary stimulation of the adrenal cortex.
Studies on the Immunization of Swine against Infection with the Swine Influenza Virus
Authors: McLean I. W. , Beard Dorothy , Beard J. W.
Published: January 2023

A disease easily characterizable and measurable in severity by clinical observations on the height and duration of fever, loss of weight and anorexia was produced in normal, unvaccinated swine by exposure to active swine influenza virus contained in chick-embryo chorio-allantoic fluid. The animals were uniformly highly susceptible to infection, giving a morbidity score of 94.1 per cent, but no deaths occurred. There was no evidence of synergistic bacterial infection.

Vaccination with formalin-inactivated, purified swine influenza virus given subcutaneously produced an overall reduction in the incidence and severity of the clinical disease, resulting in a morbidity score of 59 per cent. No significant difference could be seen between the effects of 1, 2 or 3 injections of 0.5-mg amounts of the inactive virus, though the respective morbidity scores were numerically slightly smaller with repeated vaccinations. The results were not related to the age or size of the animals nor to the time of year of the tests. The antibody titers of the vaccinated animals were consistently greatly increased following exposure to active virus, whether symptoms developed or not. The levels of antibody titer 2 weeks after exposure to active virus were related directly to the number of vaccinations preceding the exposure.

The degree of immunity or resistance conferred by vaccination, 37 per cent, was far less than that induced by exposure to active virus, 82 per cent, regardless of the severity or mildness of the disease, and the same was true for animals tested with active virus a second time after previous vaccination and exposure to active virus. The levels of antibody titer of animals in these categories rose little, or not ar all, on repeated exposure to active virus, indicating a very low degree, if any, of asymptomatic infection under these conditions.

The findings are discussed in relation to their bearing on the control of influenza in man by vaccination.
The Effect of Tubercle Bacilli on the Antigenicity of a Synthetic Ester of Oleic Acid
Authors: Middlebrook Gardner , Dubos René J.
Published: January 2023

Injection of rabbits with formalin-killed human or avian tubercle bacilli grown in a medium containing the synthetic water-soluble oleic acid ester, “Tween 80”, elicits the production of serum antibodies capable of precipitating this synthetic ester. Tubercle bacilli grown in the presence of “Tween” or artificially coated by “Tween” are agglutinated by such sera in high titer. “Tween 80” per se is non-antigenic when given intravenously to rabbits under the conditions studied. Serological cross-reactions occur between “Tween 80” and various other chemically related water-soluble fatty acid esters.
Diagnostic Antigens for Epidemic Typhus, Murine Typhus and Rocky Mountain Spotted Fever
Authors: van der Scheer James , Bohnel Emil , Cox Herald R.
Published: January 2023

Epidemic typhus and murine typhus vaccines prepared from infected yolk-sacs by ether-extraction process give nonspecific reactions in complement-fixation tests with Wassermann-positive human syphilitic sera if the technic of fixation for 18 hours at icebox temperature is used.

Purified and concentrated soluble antigens were prepared from epidemic typhus, murine typhus and Rocky Mountain spotted fever vaccines by further treating the ether-extracted preparations with benzene followed by precipitation with sodium sulfate.

The purified soluble antigens gave little or no reaction with human syphilitic sera using complement-fixation at icebox temperature.

Complement-fixation tests with the purified and concentrated soluble antigens clearly differentiate cases of epidemic and murine typhus from Rocky Mountain spotted fever and will often, but not always, distinguish between epidemic and murine typhus cases.
The Technic of Collodion Particle Agglutination
Authors: Cavelti Philip A.
Published: January 2023

The technic of collodion agglutination is described in detail, including the preparation of collodion particles and means to control nonspecific reactions.
Colorado Tick Fever
Authors: Koprowski Hilary , Cox Herald R.
Published: January 2023

The mouse brain adapted Florio strain of Colorado tick fever virus was cultivated by yolk-sac passage in the developing chick embryo through 78 generations. The virus multiplied slowly and reached its maximal titer on the 4–5th day after inoculation.

Experiments indicated that virus is present in significant amounts only in the central nervous system.

The virus retained its virulence for intracerebrally inoculated mice but lost its invasive power for mice and hamsters inoculated parenterally.

The virus introduced parenterally in minimal amounts elicited an immune response in mice which withstood subsequent intracerebral challenge with mouse brain virus.

The 37th egg passage of the virus injected subcutaneously into four volunteers caused only minor clinical manifestations and induced the formation of homologous virus-neutralizing antibodies in all four vaccinated individuals.
The Significance of Protection Tests with the Serum of Man and Other Animals against the Lansing Strain of Poliomyelitis Virus
Authors: Hammon W. McD. , Mack W. N. , Reeves W. C.
Published: January 2023

Seventy-eight per cent of the sera from 55 domestic cows from Western States and Okinawa neutralized the Lansing strain of poliomyelitis virus while of 18 “controls” from Nevada desert range none protected. In fresh bovine sera antiviral substances were frequently present which disappeared after storage for 2 or 3 months. Sixty-seven per cent of a similar group of 48 horses were positive and only one of 15 desert controls protected. Forty-four per cent of 112 domestic or “exposed” chickens were positive while only 2 of 43 controls sheltered in the laboratory protected. Of other domestic mammals 45 per cent of 58 protected while none of 30 from wild species were positive. Of domestic birds other than chickens 30 per cent of 63 protected while 19 per cent of 26 from wild species were positive. None of 31 sera from laboratory monkeys, guinea pigs, rabbits, pigeons or doves were positive. Sera from many of these had high titers to one or more of the encephalitis viruses. Monkeys, cotton rats and hamsters inoculated with monkey cord virus of a strain immunologically related to the Lansing strain (MEF-1) responded with neutralizing antibodies though showing no other signs of infection. Three other strains of virus (Brock, Lemos and Bigelow) produced no such response. Chickens inoculated with MEF-1 and other virus strains did not develop antibodies. Furthermore, serum from chickens frequently behaved in an irregular and unexplainable manner. No virus could be isolated from the feces of chickens which were fed or were inoculated with a freshly isolated poliomyelitis virus. Paired, two phase sera from 102 poliomyelitis patients gave the following results: 84 had a high titer at onset or showed no change; 10 showed an increase and 8 a decrease. Few of the human sera taken at onset gave an equivocal result; they tended to be either definitely negative or positive. Fifty-seven of 84 were positive. It is concluded that some strains of poliomyelitis virus fail to stimulate any or significant titers of antibody to the Lansing strain and that others do, this probably is the result of antigenic differences. However, it is far from being established that all Lansing antiviral substances encountered in man or animals are due to contact with poliomyelitis virus.
Preparation of an Antigen Mixture from H. Pertussis by Selective Denaturation
Authors: Hink John H. , Johnson Frederick F.
Published: January 2023

A simple method is given for obtaining a partially purified mixture of antigens from H. pertussis organisms. Certain physical and chemical properties of the antigens are described. The use of the antigen mixture as an agent for distinguishing between normal rabbits and rabbits immunized with Merthiolate-killed H. pertussis suspensions is reported. Electrophoretic separations were performed and the resultant data show that at least two antigens are recovered. One of these absorbs agglutinins but seems not to contain “skin-test” activity. The other has “skin-test” activity and its lack of agglutinin absorbing activity is suggested but not proved by the present data.
Latent Mouse Encephalomyelitis
Authors: Melnick Joseph L. , Riordan John T.
Published: January 2023

These observations are concerned with the chance occurrence of latent mouse encephalomyelitis, either the paralytic TO or encephalitic FA type, in normal stock Swiss mice.

In the course of experiments utilizing about 40,000 mice purchased chiefly from two animal dealers, the TO type of encephalomyelitis was encountered spontaneously in 4 instances, and following non-specific inoculations in 3 instances. The FA virus was found to be the cause of encephalomyelitis occurring in one instance spontaneously, and in 7 instances following intracerebral inoculation of non-infectious material or of murine-adapted strains of human poliomyelitis virus.

In the latter instances, the inoculated murine-adapted virus and the contaminating FA strain were separated into pure lines of each strain. The contaminated murine-adapted human strains were freed of FA virus by treatment with FA hyper-immune serum or by passage through the monkey, a host which is not susceptible to the FA virus. FA virus was readily obtained from the mixture of strains by serial passage of brains of mice showing only encephalitic signs or by passage through chick embryos.

The virus strains were identified by complement fixation and/or virus neutralization tests as well as by their host spectrum and “clinical” signs.

There was no evidence that the interference phenomenon prevented the simultaneous passage of the Lansing and the FA strains through several serial transfers in mice.
Induced Resistance to Streptomycin
Authors: Seligmann Erich , Wassermann Michael
Published: January 2023

Some chromogenic bacteria and a group of salmonella strains were “trained” to high streptomycin resistance in vitro. A few equally resistant strains were recovered from streptomycin treated patients. Acquired resistance is accompanied by marked alteration of metabolic activities of the bacteria. Decreased rate of growth and of reducing intensity, changed fermentation of carbohydrates and protein derivatives (H2S production), loss of pigment formation of B. pyocyaneus, loss of animal pathogenicity in salmonellae are the main indications of a damaged enzymatic system. No streptomycin destroying qualities develop in resistant strains. It is suggested that induced resistance to streptomycin is not so much the result of a selective process but rather the physiological response of the bacterial cell against the damaging drug. The mode of drug action and clinical implications are discussed.
Chemotherapy of Virus Infections
Authors: Cutting Windsor C. , Dreisbach Robert H. , Halpern Richard M. , Irwin Elizabeth Ann , Jenkins Doris W. , Proescher Frederick , Tripi Helen B.
Published: January 2023

Chemotherapy has become increasingly effective in attenuating the striking power of protozoal and bacterial diseases, but, except in isolated instances, this approach to the control of virus diseases has been unsuccessful. The exceptions, lymphopathia venereum, trachoma, inclusion blenorrhea, mouse pneumonitis and some members of the ornithosis group, are susceptible in varying degree to sulfonamides and penicillin (1). In a sense, this susceptibility to chemotherapeutic attack separates these diseases from the greater number of virus infections and suggests their more immediate descent from bacteria responsive to usual chemotherapeutic measures. It should be noted even here, that while the animals may be saved, active virus can sometimes be recovered from them. Although infections by viruses other than the noted exceptions may be influenced, and even controlled, by natural immune bodies, and by “interference” from other viruses, ordinary medicinal therapy has failed completely.
Studies in Dysentery Vaccination
Authors: Cooper Merlin L. , Keller Helen M.
Published: January 2023

Active immunization of mice with vaccines of Shigella sonnei, Shigella ambigua, Shigella flexneri VI (Boyd 88) and Shigella flexneri III-Z followed by homologous and heterologous challenge infections demonstrated consistently a higher degree of homologous than heterologous immunity.

Active hyperimmunization of mice first with vaccine of Shigella flexneri III-Z, then by injection with many LD50 doses of living homologous Shigella, stimulated a higher degree of heterologous immunity against Shigella flexneri II-W than occurred in mice immunized with vaccine alone.

Active immunization of mice with a Seitz filtrate of broth culture and a Seitz filtrate of saline suspension of an agar culture of Shigella flexneri III-Z stimulated surprising amounts of homologous immunity.
A Single-Dilution Method for the Estimation of LD50 Titers of the Psittacosis-LGV Group of Viruses in Chick Embryos
Authors: Golub Orville J.
Published: January 2023

It has been demonstrated with several members of the psittacosis-LGV group of viruses that there exists a linear relationship between the concentration of virus inoculated into eggs by the yolk-sac route and the average day of death of the embryos. By plotting of repeated large scale titrations according to the average day of death at each dilution and the LD50 values obtained, an average line is drawn from which it is possible to estimate directly the LD50 value of a virus suspension from the average day of death of a group of eggs inoculated with one dilution. The linear relationship has been shown to hold with two strains of psittacosis virus (Gleason and 6BC), meningopneumonitis virus (Cal 10), and Louisiana pneumonitis virus (Borg).

It is possible to use either eight or nine day old embryonated eggs, the resulting titer differences being within the limits of error of the test.
Some Factors Influencing the Selection of a Complement-Fixation Method
Authors: Rice Christine E.
Published: January 2023

Requirements in regard to accuracy and the difficulties likely to be encountered in evaluation of the results are the two major factors governing the selection of a quantitative complement-fixation method. In this paper, two quantitative complement-fixation procedures are evaluated on these bases.

If only a rough estimate of antibody activity is needed, the serum dilution titer determined by method 1 is adequate. If however a more precise measurement of antibody content is required, method 2 will prove more satisfactory. Especially will this be the case in comparison of the relative efficiency of different methods of preparing antigen, in determination of antigenic relationships or in measurement of the relative specific, non-specific and cross-activities of a serum.

When antigens are crude containing relatively large amounts of extraneous material, method 1, which employs a lower antigen dose may be preferable. If so, calculation of the increment ratio titer as indicated in the second section of this paper, may give a more precise estimate of titer than the usual method of recording serum-dilution titers in terms of the dilution factor. Not only do the increment ratios provide a sharper differentiation in relative titers than the latter, but they enable the reactions of anticomplementary sera to be recorded in numerical terms. Furthermore, it is possible to introduce a correction factor for variation in the stability of different lots of complement during preliminary incubation. The use of increment ratios in defining the relative “specific” and “nonspecific” activities of sera is also described.
The Inactivation of Influenza Virus by Mercurials and the Reactivation by Sodium Thioglycolate and Bal
Authors: Klein Morton , Brewer J. H. , Perez J. E. , Day Beatrice
Published: January 2023

Six mercurials were tested for their in vitro activity against influenza virus. HgCl2, merbromin, merodicein, metaphen and phenyl mercuric nitrate effectively inactivated influenza virus. Merthiolate possessed little in vitro activity against influenza B virus. Merodicein instilled intranasally possessed some prophylactic activity against influenza virus.

The inactivation of influenza virus by HgCl2 could be reversed in vitro with either sodium thioglycolate or BAL. The intramuscular injection of BAL also effected the in vivo reactivation of the virus.
Preparation of Diphtheria Toxin Solution Requiring no Control in the Schick Test
Authors: Ross Victor
Published: January 2023

Summary and Conclusions

The results of the lethal and intradermal tests in guinea pigs clearly show that the proposed diluent, consisting of a peptic digest of human serum proteins, acts as an effective stabilizer of the very dilute solution of diphtherial toxin used in the Schick test. After being held at 2 C. for 27 months no loss in activity was detected.12 The new solution possesses, therefore, good preserving power, an indispensable requirement of any proposed diluent for this toxin.

Of the 24 subjects who were seen 24 hours after the injections and daily thereafter only two showed some reaction at the site of the new control, in both instances this lasted only one day and was negligibly small. Of the 28 individuals who were not seen for the first time until 72 hours after the injections there were three who showed some reaction at the site of the new control; in one instance the erythema persisted to the eleventh day, in the other two it disappeared between the 7th and 10th days. In all three it was so small (2 × 2 or 2 × 3 mm) at all times as to make it appear that it was due to trauma, at least in part. In no instance would the omission of the control injection have resulted in a different Schick reading. The removal of “bacillary protein”, the large reduction in broth “nitrogen” and the use of the new diluent seem therefore to have accomplished the purpose of eliminating the need for a control injection in performing the Schick test.

It would seem, that the best time for making a reading is the fourth or fifth day after the injection. In every instance but one among the persons read as Schick-positive with the new toxin the erythema measured greater than 20 mm in one direction at its height; in this one case the dimensions were 12 × 6 mm.
The Action of Urea and Some of Its Derivatives on Bacteria
Authors: Weinstein Louis
Published: January 2023

Summary and Discussion

The experiments reported in this paper indicated that hexyl carbamate was able to produce inhibition of growth of several gram-negative and gram-positive bacteria. The concentration of this compound required to suppress bacterial multiplication was found to be less than that necessary with urea, urethane, propyl or isopropyl carbamate, and butyl or isobutyl carbamate. These results emphasize the previously recorded observation that an increase in the number of carbon atoms in the alkyl chain replacing one of the—NH2 groups in urea results in augmentation of antibacterial activity. A concentration of the hexyl compound sufficient to kill bacteria could not be obtained; this was probably due to its relative insolubility.
Inhibitory Effects of Certain Avian and Mammalian Antisera in Specific Complement-Fixation Systems
Authors: Rice Christine E.
Published: January 2023

The results of quantitative studies of the inhibitory effect of non-complement-fixing antipullorum avian and antipneumococcus horse sera on fixation of complement by homologous rabbit antisera and antigen have been described. These data have indicated that the degree of inhibition is dependent not only upon the relative antibody content of the antisera of the two species concerned but also upon the quantity of antigen present.

The possible application of the inhibition reaction, indirect complement-fixation test, in the assay of antibody content has been discussed and a tentative method of titrating this inhibitory activity outlined in which the sensitivity is adjusted to a level approximately comparable to that of the direct complement-fixation test.
Therapy of Experimental Brucella Infection in the Developing Chick Embryo
Authors: Hall Wendell H. , Spink Wesley W.
Published: January 2023

Summary and Conclusions

A method is described whereby the efficacy of therapeutic agents against Brucella may be ascertained by injection into the allantoic sac of the developing chick embryo. The results of studies with streptomycin and several sulfonamides in shick embryos infected with Br. abortus and Br. suis are reported. Sulfadiazine and streptomycin in combination were found to be more effective against Br. abortus and Br. suis in the infected chick embryo than either drug alone.
Microbal Studies on Acute Respiratory Infection with Especial Consideration of Immunological Types
Authors: Park William H. , Williams Anna W. , Krumwiede Charles
Published: January 2023

Introduction. Outline of work planned, discussion of results and general conclusion. It was decided at a conference of the members of the Influenza Commission and the Research Laboratory workers that the problems to be investigated in New York City should be the following: A study of the microörganisms of the upper respiratory tract in “health,” in “common colds” and in “influenza.” This investigation should include the diligent search for an epidemic microbal strain in influenza cases. Both filtrable and unfiltrable microbes were to be considered.A continuation of our studies on hemoglobinophilic bacilli (group of the influenza bacilli) for the purpose of establishing the relationship of the influenza bacillus to both pandemic and sporadic cases of influenza.A study of the permanence of type characteristics of influenza bacilli in persons after recovery from respiratory infections. It was considered of the utmost importance to establish as accurately as possible the stability of types.