bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Lymphogranuloma Venereum Complement-Fixing Antigens
Authors: Hilleman Maurice R. , Nigg Clara
Published: January 2023

A lymphogranuloma venereum complement-fixing antigen was extracted from infected yolk sac suspensions with anesthetic ether. The activity of the ether extract antigen represented four- to eight-fold enhancement. Maximal enhancement in the ether extract antigen depended on (a) preliminary aging of the yolk sac suspensions, (b) degree of dispersion of the extract in saline solution, and (c) absence of phenol. The purified ether extract antigen possessed the same complement-fixing group reactivity as phenolized unextracted antigen. The similarity of extract antigen to glucolipid fractions of bacterial origin was discussed.
Studies on Lymphogranuloma Venereum Complement-Fixing Antigens
Authors: Bowser Betty M. , Nigg Clara
Published: January 2023

A high percentage of serums from patients in the early stages of syphilis gave complement fixation reactions with phenolized boiled antigens prepared either from yolk sacs infected with lymphogranuloma venereum or from normal yolk sacs. Such nonsepcific reactions preclude a serological diagnosis of lymphogranuloma venereum. The nonspecific reactions observed with syphilitic serums were completely eliminated by using phenolized boiled supernate-antigens. Phenolized boiled supernate-antigens prepared from yolk sacs infected with lymphogranuloma venereum also gave positive complement fixation reactions with the serums of patients recovered from psittacosis and ornithosis. These cross reactions emphasize the close antigenic relationship within the psittacosislymphogranuloma venereum group of viruses.
The Recovery of Poliomyelitis Virus from the Stools of Experimentally Infected Monkeys and Chimpanzees
Authors: Melnick Joseph L.
Published: January 2023

Following the inoculation of various strains of poliomyelitis virus into monkeys and chimpanzees by various parenteral routes, virus has been detected in the stools of seven primate species. Finding poliomyelitis virus in stools and intestinal contents in the monkey or chimpanzee is not sufficient evidence to point to the mouth as the portal of entry. The experiments do not indicate however whether the virus may be excreted first into the upper part of the alimentary tract and subsequently find its way to the intestines. In each of two chimpanzees a “healthy” carrier state lasting two and four weeks respectively developed following intracutaneous inoculation of the SK strain. A third chimpanzee that became a virus carrier had only slight transitory symptoms in the second week following inoculation. Virus appeared in the stools of some animals before any symptoms of the disease in the central nervous system were apparent.
Psittacosis Vaccines Prepared from Chick Embryo Tissues
Authors: Wagner J. C. , Meiklejohn G. , Kingsland L. C. , Hickish H. W.
Published: January 2023

Psittacosis (strain 6 BC) vaccines have been prepared which, following 3 intraäbdominal injections of 0.5 ml each, protected 75 percent or more mice against intraäbdominal challenges of 10,000 to 1,000,000 LD50 of the virus, and conferred definite protection against small challenges (1 to 10 MLD) by the respiratory and intracerebral routes. The best vaccines were prepared from infected yolk-sacs by a procedure which involved lyophilization prior to ether extraction. Such vaccines were extremely rich in elementary bodies. The immunizing potency of vaccines appeared to be related to their elementary body content. The complement-fixing antigenic titer of vaccines appeared to have no relation to immunizing potency.
Studies in Human Malaria
Authors: Mayer Manfred M. , Heidelberger Michael
Published: January 2023

As a test for latent malaria the complement fixation reaction with any of the antigens described has proven of only limited value. In chronic relapsing vivax malaria an auto-antibody is often associated with relapses and parasitemia and may be detected with normal human stromata. The “soluble” purified vivax antigen does not react with the auto-antibody but appears to indicate a specific malarial response unrelated to the patient's state of immunity. This antigen, as well as gallinaceum antigen, contains substances reactive with Wassermann antibody.
Studies on the Chemotherapy of Viruses in the Psittacosis-Lymphogranuloma Group
Authors: Wiseman Robert W. , Meiklejohn Gordon , Lackman David B. , Wagner John C. , Beveridge Gerald W.
Published: January 2023

Penicillin showed a definite therapeutic effect when given by the subcutaneous route to mice infected with Gleason strain of psittacosis, the Borg Strain, pigeon ornithosis virus (P 207), meningopneumonitis virus (Cal 10), and mouse pneumonitis virus (Nigg). Oral sulfadiazine was effective in mice infected with the two psittacosis strains and the mouse pneumonitis virus, but not in mice infected with the Borg Strain, SF Strain, Pigeon Ornithosis Virus (P 207), Meningo-pneumonitis Virus (Cal 10), and feline pneumonitis virus. Results obtained with the two drugs in mice were, in each instance, in agreement with those obtained in chick embryos.
The Immunochemistry of Toxins and Toxoids
Authors: Pillemer Louis , Grossberg Donald B. , Wittler Ruth G.
Published: January 2023

Methods employing methanol under controlled conditions of pH, ionic strength and temperature are described for the purification of tetanal toxoid. The antigenicity and the flocculative power of the purified material are quantitatively recovered and are concentrated about 300 times on a nitrogen basis over the parent toxoids.

The purified toxoids do not shock guinea-pigs sensitized to culture medium, indicating that they are relatively free of anaphylactogenic properties.

Procedures are given for the processing of the purified material to a stable state suitable for assay and immunization. Freezing and drying, sterile filtration in the presence of glycine and alum-precipitation do not alter the antigenic values of the purified tetanal toxoids.

The considerations discussed in the text suggest that the purified toxoids may prove useful for immunization of man against tetanus.
Standardization of the Cardiolipin-Lecithin-cholesterol Antigen in the Complement-Fixation Test with Cerebrospinal Fluid
Authors: Maltaner Elizabeth , Maltaner Frank
Published: January 2023

The study of cardiolipin antigen with cerebrospinal fluids supplements one previously made with serum to demonstrate the relationships between the three constituents—cardiolipin, lecithin, and cholesterol—essential to the standardization of the test.

Neither cardiolipin nor lecithin alone had antigenic action with cerebrospinal fluids. In contrast to the results with serum, the anticomplementary activity of cardiolipin was somewhat more marked in the presence than in the absence of cerebrospinal fluids.

Mixtures containing lecithin and cardiolipin, without cholesterol, in ratios between 3:1 and 10:1 were highly antigenic. Raising or lowering the proportion of lecithin diminished the reaction.

In cholesterolized mixtures the ratio of cholesterol:lecithin required for optimal reaction gradually increased as the lecithin:cardiolipin ratio decreased; namely, from 2:1 in solutions containing lecithin:cardiolipin in ratio of 20:1, to 5:1 in solutions containing lecithin and cardiolipin in ratio of 1.25:1. However, the several optimally sensitized solutions containing lecithin and cardiolipin in ratios varying from 20:1 to 1.25:1 did not differ as markedly in reactivity with cerebrospinal fluids as they did in tests of serum.

Anticomplementary reaction appeared in cholesterolized solutions containing as little as 1.25 parts of lecithin to 1 of cardiolipin.

A solution containing lecithin and cardiolipin in ratio of 5:1 and cholesterol in ratio of 3.4:1 with lecithin such as was previously recommended for use in tests of serum appears satisfactory also for use with cerebrospinal fluids. The composition of the antigen used and the saline dilutions required for optimal reaction in the quantitatively standardized complement-fixation test are indicated.
Studies of Antipneumococcal Serum
Authors: Rice Christine E. , Sickles Gretchen R.
Published: January 2023

The complement-fixing activities of fractions of one pooled normal and three pooled antipneumococcal rabbit sera (types 2, 3, and 7) have been studied quantitatively in the presence and absence of homologous type-specific carbohydrate antigen.

Considered in relation to total nitrogen content, the water-insoluble globulin was, of these fractions, the most anticomplementary; the concentrated water-soluble globulin fraction had about the same degree of anticomplementary activity as the original serum; the albumin fraction had a negligible effect on complement.

In titrations of the activities of the various fractions of antipneumococcal sera with homologous type-specific carbohydrate, a somewhat better agreement was noted between W, the maximally reactive dose of antigen, and η, the amount of antibody nitrogen present, than between η and K', the number of units of complement required for 50-per-cent hemolysis. Although individual preparations differed in this respect, this observation suggested that the procedures of fractionation might have affected the combining activity of antibody with antigen less than its complement-fixing capacity in the presence of the same antigen.
Studies on Chick Embryo Vaccines Against Japanese B Encephalitis
Authors: Koprowski Hilary , Cox Herald R.
Published: January 2023

The preparation of formolized vaccines from chick embryo tissue infected with Japanese B encephalitis virus has been described.

The chick embryo vaccines showed much lower immunogenic power than mouse brain vaccines when they were submitted to the mouse potency test required by the National Institute of Health.

The apparently inferior antigenic qualities of chick embryo preparations seemed to be related to the conditions set forth by the “NIH test,” viz., to the fact that both vaccination and challenge inoculation of mice were done by the same route.

When mice were vaccinated by intraäbdominal route and challenged by intravenous route, the immunogenic power of vaccines prepared from chick embryo tissue was found to be comparable to that of mouse brain vaccines.

One out of four individuals vaccinated with mouse brain vaccine showed the presence of specific neutralizing antibodies in her serum drawn after vaccination, while one out of three individuals vaccinated with chick embryo preparation developed neutralizing antibodies. A fourth individual vaccinated with chick embryo vaccine developed neutralizing antibodies but since this individual had received an injection of mouse brain vaccine six months previously, an anamnestic response could not be ruled out.

The findings are discussed and the conclusion is reached that in view of the potential danger involved in vaccinating humans with preparations derived from nervous tissue, chick embryo vaccines should be studied for the purpose of replacing mouse brain vaccines.
Further Experimental Studies on the Rôle of the Plasma Cells As Antibody Producers
Authors: Bjørneboe M. , Gormsen H. , Lundquist Fr.
Published: January 2023

By intensive immunization of rabbits with a mixture of 8 pneumococcus types the authors have produced a very massive plasma cell infiltration (90 per cent) and a slight lymphocyte infiltration (10 per cent) in the adipose tissue of the renal sinus. Extracts of this adipose tissue of the renal sinus, rich in plasma cells, contain considerable amounts of antibody-protein, essentially more than is found in the extracts of any other organ from these animals.

From these findings and from their previous observations employing the same experimental technic the authors advance the hypothesis that antibodies are produced by plasma cells.
A Specific Antigen Recovered from Tissue Infected with M. Paratuberculosis (Johne's Bacillus)
Authors: Sigurdsson Björn
Published: January 2023

The specific paratuberculosis antigen found in the intestinal mucosae of sheep with Johne's disease was further investigated.

The antigen is quite resistant to low pH, but it is insoluble between approximately pH 3 and pH 5. Preliminary extraction of dried and ground mucosa at pH 4 to 4.5 will render subsequently prepared antigenic extracts more active, this is believed to be due to the removal of an inhibiting substance in the acid extract.

No matter whether this preliminary extraction has been employed or not, it is best to carry out the antigenic extraction itself at about pH 9 and at 100 C, for one hour.

As has previously been shown, a thorough mechanical grinding of the dried tissue is the most effective means of demasking the antigen in the mucosa. It was found that grinding in a ball-mill is much more effective than grinding by hand in a mortar. Also, that there is an optimum length of time that the tissue should be ground, since longer grinding again reduces the activity.
The Antigenic Specificity of Syphilitic Antibody Globulin
Authors: Henriksen Sverre Dick
Published: January 2023

Washed Wadsworth-Brown floccules, presumably consisting of lipoid antigens in combination with syphilitic antibody, evoke in rabbits two different antibodies, one against the lipoid antigen, the other against syphilitic antibody. Rabbit anti-syphilitic-antibody reacts equally well, and with high dilutions, with both normal and syphilitic human serum. It reacts with the total globulin fraction of normal serum to the same titer as with whole serum, and with water-insoluble globulin to an only slightly lower titer. The water-soluble globulin gives reaction only in 8 to 10 times higher concentration, and the albumin in 1000 times higher concentration. The specificity of syphilitic antibody seems to be the same as that of certain normal serum globulins. It seems to be more closely related to the euglobulin fraction than to the pseudoglobulin.
Detoxification of Crystalline Botulinum Type A Toxin
Authors: Hottle G. A. , Abrams A.
Published: January 2023

Botulinum Type A toxoid has been prepared from crystalline toxin by the addition of formaldehyde. The most active preparation consisted of one component electrophoretically, immunized mice in a dose containing 0.01γ of toxoidnitrogen and was 2400 times more active antigenically than crude toxoid on the basis of nitrogen-content.
Immunization of Humans and Animals with Gas Gangrene Toxoids
Authors: Tytell Alfred A. , Logan Milan A. , Tytell Alice G. , Tepper Jack
Published: January 2023

Alum precipitated Cl. perfringens and Cl. oedematiens toxoids have been prepared from potent toxic filtrates. These toxoids have been demonstrated to be effective in producing a measurable and protective titer of antibodies in mice, guinea pigs, rabbits, goats, dogs and humans. In the animals, good protection against multiple doses of toxin and culture has been obtained. Protection of animals against heterologous as well as homologous strains of culture was demonstrated. Titers have been regularly achieved in humans which in smaller animals have shown good protection against toxin and culture challenge. In humans, very little rise of antitoxin titer was observed after one dose of Perfringens toxoid Lb=15. After two doses 50 to 75 per cent of individuals showed fairly good titers. When a third dose was given 3 to 9 months after the second dose excellent titers were obtained in practically all individuals and these titers were maintained for at least seven months. Good protective titers against Oedematiens were obtained with two doses of toxoid of as low a potency as 40 test doses (Lb=0.8). Very good response was obtained to a third dose of toxoid at 16 weeks after the second dose. Divalent toxoids (Perfringens-Oedematiens) have been prepared by mixing adequate amounts of the monovalent alum toxoids. These divalent toxoids have shown very adequate protective response (antibody titers and protection against toxin and culture) in mice, guinea pigs, rabbits and goats. Trials in humans have shown adequate response to three (3) doses of toxoid. The toxoids made for human use were prepared on a commercial scale and passed all safety tests as outlined by the National Institute of Health. The alum toxoids tested in humans did not produce local or systemic reactions in a great majority of the volunteers tested. Where reactions were obtained they were in a majority of the cases not as severe as those produced by alum tetanus or diphtheria toxoids or typhoid vaccine. Tests of the antigenicity of various toxoid preparations in mice and guinea pigs are given for comparison with the response subsequently obtained in humans. Data on the immunization of dogs and goats are also given.
Studies on Botulinum Toxoid, Types A and B
Authors: Hottle G. A. , Nigg Clara , Licthy J. A.
Published: January 2023

Introduction. The need for standardizing methods of measuring the biological activity of toxoids is generally recognized. Antigenicity is frequently assayed by qualitative or crudely quantitative methods. Mueller et al (1), in reporting their work on tetanus toxoid, have emphasized the need for precise methods of determining antigenicity since they found that there were “tremendous individual variations among guinea pigs in ability to respond to identical stimuli”.

Two methods have generally been used for the in vivo evaluation of toxoids. In one method immunity is challenged by injection of toxin, and the degree of resistance to this challenge is used as a measure of the antigenicity of the toxoid. In the other method the average serum antitoxin titer of the immunized animals is used as an index of the antigenicity of the toxoid.
A Comparative Study of Pathogenicity and Antigenicity of Four Strains of Herpes Simplex
Authors: Florman Alfred L. , Trader Frederick W.
Published: January 2023

Comparative studies of pathogenicity and antigenicity were made of four strains of herpes simplex in order to investigate some of the differences which may exist between strains of a single viral species. Mice, rabbits, guinea pigs, white rats, hamsters, cotton rats and chick embryos were observed after inoculation of mouse brain emulsions by various routes. Although herpes simplex is a pantropic virus, differences between strains are accentuated by certain tests. Thus, death of the majority of animals following corneal infection of the rabbit or intranasal inoculation of the cotton rat can be used to indicate strains with prominent neurotropic tendencies, while marked local reactions after intradermal injection of the guinea pig are indicative of dermatotropism. These distinctions probably hold only for the particular species of animals and routes tested, as the strain which was most dermatotropic in our laboratory, “O”, was the cause of fatal encephalitis in a human being. It is not known whether these differences in potentiality of herpes strains are of epidemiologic significance. The development of neutralizing antibodies in rabbits after corneal and intra-abdominal inoculations was studied. Significant levels of antibody were present by three weeks and peak titers were attained by six weeks. The serologic relationships were investigated by testing the corneal reactivity of immunized rabbits to homologous and heterologous strains and by cross neutralization tests in mice and chick embryos. The chick embryo tests were found to be the most sensitive and satisfactory for this purpose.
The Clinical Behavior, Incubation Period, and Pathology of Tetanus Induced in White Swiss Mice by Injection of Crystalline Tetanal Toxin
Authors: Pillemer Louis , Wartman William B.
Published: January 2023

Intramuscular administration of 0.000013 gamma of crystalline tetanal toxin nitrogen produced the classical signs of tetanus in white mice weighing between 15 and 20 grams. Incubation period was about 30 hours and death occurred in 96 hours.

Intramuscular administration of 6.4 gamma of crystalline tetanal toxin nitrogen or 500,000 MLD led to appearance of symptoms within 30 minutes and death in 60 minutes. The chief clinical signs were fixation of the muscles of the thorax and abdomen, respiratory embarrassment, increased muscular tonus and asphyxia.

These results indicate that, in white mice injected with crystalline tetanal toxin, the so-called incubation period is dependent upon the amount of toxin administered and can be varied at will.

No pathological lesions were produced in white mice which received single doses of crystalline tetanal toxin ranging from 0.25 MLD to 500,000 MLD and which lived from one hour to 28 days after injection of the toxin. Similar results were obtained when repeated sublethal doses of toxin were given.
Complement-Fixing Antibodies of Lymphogranuloma Venereum in Mice: Their Development and Response to Sulfonamide Therapy
Authors: Wall Margaret J.
Published: January 2023

A study has been made of the development of complement-fixing antibodies in mice following infection with the virus of lymphogranuloma venereum. Antibody usually could be detected at 1 week and was always demonstrable at the end of 2 weeks after inoculation. A peak in titer was reached 3 to 5 weeks after infection. A high titer persisted throughout the 18-week period of observation. Virus could be recovered from the brains of the animals at any time after the appearance of signs of illness and throughout the period of recovery.

A remarkable correlation was found to exist between antibody-titer and the timing and duration of sulfonamide therapy. Animals treated from the time of inoculation for a period of several weeks gave negative tests for antibodies at the end of this time. In mice treated after the infection had been established, titers of antibody were lower than in control animals, and a definite relationship was found between the end-titer and the duration of therapy. When therapy was continued for several weeks, the antibodies disappeared completely. Virus could still be recovered from the tissues of these animals, but the ease with which it was isolated depended upon the program of chemotherapy.
Dysentery
Authors: Weil A. J.
Published: January 2023

Introduction. In 1943, a review of the dysentery problem was published in this Journal (272), which was prepared in the expectation that the exigencies of the war would stimulate the interest in this field. This expectation has not been disappointed. Enough new data have been published in the intervening time to make it advisable to pause again for a consideration of the harvest that has accrued.

As in the previous review, the presentation has been focused upon the points where new information has accumulated. And the clinical aspects of the problem have been left aside, which could be done with the more ease as references to clinical work will be abundantly found in Felsen's compilation (103) and in the new edition of Manson-Bahr's monograph (176).

This paper restricts itself essentially to the data since November 1942. Thus references to previous work will have to be sought in the preceding paper.
The Purification and Concentration of Influenza-Virus by Means of Alcohol Precipitation
Authors: Cox Herald R. , van der Scheer James , Aiston Stewart , Bohnel Emil
Published: January 2023

Experiments are reported in which ethyl and methyl alcohol were used to concentrate and partially purify the PR-8, Weiss and Lee strains of influenza-virus under carefully controlled conditions of alcohol-concentration, temperature and pH. Of the two, methanol was found to be superior since the optimal concentration is of broader range and less denaturation of viral protein is encountered than with ethanol. The data indicate that methanol-precipitation under controlled conditions produces no virus-denaturation nor loss of activity as judged by CCA activity, infectivity titers in chick-embryos or immunizing potency of killed vaccines for mice. On the contrary, based on the CCA activity of the starting material, yields of virus equal to or exceeding 100 per cent are obtained. The methanol-precipitation method is readily applicable to the concentration and purification of influenza-virus using either the bucket, angle head or Sharples continuous-flow types of centrifuges. The method is particularly valuable from the standpoint of producing vaccines on a large scale since it may be combined readily with the Sharples centrifuge method and thus effect great savings in man and machine hours. Preliminary experiments also show that the method may have wide application in the concentration and purification of other viral and rickettsial agents.
The Action of Urea and Some of Its Derivatives on Bacteria
Authors: Weinstein Louis
Published: January 2023

Summary and Discussion

Butyl, and isobutyl carbamate have been shown to be bacteriostatic for a number of gram-negative and two gram-positive bacteria. The degree of this antibacterial effect was greater than that observed with other urea derivatives (2–8). Investigations of the bactericidal power of the butyl compound revealed that the lethal effect of this drug was more marked than was that of the other substances studied. These data confirm the impression that increasing the number of carbon atoms in the alkyl chain replacing one = NH2 group in urea results in an augmentation in antibacterial activity. The increase in bacteriostatic effect following the addition of sulfanilamide that had been noted with the other urea compounds was also observed with butyl carbamate. Para-aminobenzoic acid was found to be inactivated by butyl carbamate over a narrow range and for a very short period of time with low concentrations of the drug, and for longer intervals and over a wider range with larger quantities. This effect was in the same order of magnitude as that observed with the other urea derivatives except that a lower concentration of the butyl compound was required. The phenomenon of heightened anti-para-aminobenzoic acid activity resulting from addition of methyl groups to urea was confirmed with butyl carbamate.
A Continuous Flow Method of Exposing Antigens to Ultraviolet Radiation
Authors: Habel Karl , Sockrider B. T.
Published: January 2023

An apparatus has been described for irradiation of liquids in a continuously flowing thin film without the use of quartz chambers. In a limited number of tests the antigenicity of rabies virus, typhoid organism suspension, and Shiga dysentery toxin inactivated by this apparatus compared favorably with that of the same materials inactivated with the Oppenheimer-Levinson apparatus.
Susceptibility and Immunity in Poliomyelitis
Authors: Nelson Norman
Published: January 2023

The virus of poliomyelitis, because of its specificity, has been a relatively difficult organism with which to work in a laboratory. Immunological studies, based upon experimentally produced disease in animals, have resulted in such a mass of difficultly interpreted evidence that one is forced to return to a restudy of the disease as it occurs in man.

Susceptibility as Indicated by Virgin Soil Outbreaks and Case Fatality Rates. Virgin soil outbreaks of any highly communicable disease give a picture of autarceologic susceptibility not obscured by previously established immunity. For instance, when measles invaded the Faroe Islands, after being absent for 65 years, everyone under the age of 65 developed the disease (1).

With our ability to recover the virus of poliomyelitis from the stools of cases, contacts, and others, we have demonstrated in poliomyelitis what Wickman and Caverly hypothesized on the basis of epidemiologic reasoning, the phenomenon of widespread infection without disease.
Studies on the Chemotherapy of the Pox Viruses
Authors: Groupé Vincent , Rake Geoffrey
Published: January 2023

A simple method for testing a variety of substances for antiviral activity against the pox group of viruses has been evolved in which serial dilutions of the substance in question were mixed with the virus and incubated in vitro before inoculation into the yolk sac of embryonated eggs. The viruses of canary pox, fowl pox and vaccinia were completely inhibited by 3,750, 7,500 and 15,000 units of commercial penicillin respectively when the virus was mixed with the penicillin and incubated in vitro before inoculation into chick embryos. An impurity or impurities present in commercial penicillin rather than penicillin itself was found to be responsible for the inhibition of canary pox virus in vitro. The antiviral activity of commercial penicillin against canary pox virus in vitro was inhibited by the presence of normal egg yolk, but was not significantly diminished when aqueous solutions were heated to 100 C for 10 minutes. Inoculation of 50,000 units of commercial penicillin prior to the inoculation of canary pox virus into the yolk sac of chick embryos significantly but not strikingly retarded the rate of death of the embryos.
Immunochemical Studies on Tobacco Mosaic Virus
Authors: Malkiel Saul , Stanley W. M.
Published: January 2023

Tobacco mosaic virus reacts as a single component in immunological systems. As has been found for other protein systems, increasing amounts of antigen added to a constant volume of immune rabbit serum produces increasing amounts of precipitate which pass through a maximum in the region of antigen excess. In general the maximum amount of antibody precipitates in the region of the equivalence zone. The ratio of antibody to antigen in the equivalence zone is variable but has a mean of about 0.25 indicating that about 60 molecules of antibody combine with each virus particle in the complex. The relationship between R and the amount of antigen precipitated is markedly curvilinear but cannot be expressed by any of the Heidelberger and Kendall equations. This curve seems to be typical of virus-antivirus systems. Electronmicrographs of the reaction product between tobacco mosaic virus and its homologous antibody show a “lattice” effect with each virus particle being separated from others by a definite, constant space, presumably the length of the antibody molecule.
Immunochemical Studies on Tobacco Mosaic Virus
Authors: Malkiel Saul
Published: January 2023

The presence of antigenic determinants common to both tobacco mosaic virus and its rib-grass strain has been confirmed by means of the quantitative precipitin technique. Immunologically independent determinants for each virus were also found. There was no serological difference found for either tobacco mosaic virus or rib-grass virus when each was isolated from widely separated plant species. Immunoehemical studies failed to indicate that there was any normal host protein as a component of any of the virus preparations.
Immunochemical Studies on Tobacco Mosaic Virus
Authors: Malkiel Saul
Published: January 2023

The rod of tobacco mosaic virus has been fractured by exposure to sonic radiations. Unfractured, intact tobacco mosaic virus recovered following this treatment exhibited identical serological findings as the control virus and therefore suffered no changes. Preparations of short rods obtained by the sonic treatment of tobacco mosaic virus showed an enhancement of the antibody combining capacity as compared to the control. This was due in part to the increment of exposed surface following sonic treatment and probably in part to the closer packing of antibody molecules on the smaller fragments. No changes in serological specificity nor the presence of any new antigenic determinants could be detected in the fractured particles of virus. This indicated that the new surfaces exposed possessed the same molecular configuration as the original surface.
A Dilution-Phenomenon in the Titration of Antivenins (Antibothropic Sera)
Authors: Eichbaum F. W.
Published: January 2023

The amount of Bothrops jararaca venom neutralized by a certain quantity of specific antiserum can be closely measured by the intravenous mouse-test The neutralizing power of Bothrops jararaca antivenin is relatively stronger at high serum-dilutions than in an undiluted state. The neutralization-curve of Bothrops jararaca antivenin can be represented by a straight line, when both the amount of neutralized venom and the amount of serum capable of effecting this neutralization are plotted logarithmically. This type of neutralization-curve is found not only when serum and venom are injected simultaneously, but also when injected 24 hours apart. Native sera and a serum which had been concentrated by treatment with Na2SO4 behaved in the same way. The neutralization-curve is represented mathematically by the adsorption-equation: log y = log a + b log x, defined in the text. The value of “a” varies according to the absolute strength of the undiluted serum; the value of “b” varied but little (around 0.62) in all sera tested under equal experimental conditions and seems to be characteristic for this type of neutralization-curve. Neutralization of the coagulase in Bothrops jararaca venom is represented by a straight line, indicating a direct proportion between the amount of neutralized coagulase and the serum-dilution effecting this neutralization.
Studies on the Reversibility of the Antigen-Antibody Reaction
Authors: Morris Marion C. , Karr Helen V.
Published: January 2023

A previous paper (1) dealing with the effects of homologous type-specific polysaccharide on the agglutination and capsular swelling of sensitized pneumococci III has shown that both agglutination and capsular swelling are reversed when suitable amounts of carbohydrate are used. The reversal of these two reactions was interpreted as being due to dissociation and redistribution of the specific antibody. With the reagents and technic used at that time, it was not possible to demonstrate that any amount of carbohydrate caused increased aggregation of pneumococci sensitized in the inhibition-zone of antibody-excess and washed free of uncombined antibody. This was contrary to expectations in view of the findings of Heidelberger and Kabat (2).

By use of a higher-titered serum and by modifying the earlier technic, it has now become possible to demonstrate increased aggregation of sensitized washed pneumococci exposed to certain concentrations of the homologus polysaccharide.
Specific Aggregation of Streptococcal Proteins Adsorbed on Oil Droplets
Authors: Boroff Daniel A. , Tripp Leonard M. , Dembeck Bernard J.
Published: January 2023

A bacterial antigenic preparation in solution may possess several specificities, some of which become apparent only under special conditions.

Adsorption of a group-specific protein (NPA) derived from streptococci Lancefield Group A, on olive oil changes the reactivity in an agglutination reaction from predominantly group-specific to predominantly type-specific.

When this protein is adsorbed on olive oil globules, it behaves serologically more like intact streptococci than when it is in solution, in that it shows a prozone in the region of antibody excess and exhibits cross-reactivity in low dilutions of antisera.

Adsorption of NPA on a non-streptococcal bacterial surface did not change the specificity of the protein from that exhibited by NPA in solution.

It is suggested that the type-specific activity of NPA complex may be due to the hapten “T”.
The Plasma Cellular Reaction and Its Relation to the Formation of Antibodies in Vitro
Authors: Fagraeus Astrid
Published: January 2023

During secondary response, elicited in sensitized rabbits by means of intravenous injections of antigen, a great increase in the number of plasma cells (pl.c.) in the spleen was recorded simultaneously with the increase of circulating antibodies. Pl.c. were confined almost exclusively to the red pulp, especially after the injection of living S. typhi. They originated apparently from reticulum cells, passing through a chain of development: transitional cell → immature pl.c. → mature pl.c. Pieces of spleen were excised at different times during the period of antibody formation in rabbits, differential cell counts were made and the capacity of excised splenic tissue to form antibodies in vitro was investigated. The following observations were made: The a mount of antibody liberated in plain tissue extracts, under conditions preventing growth or metabolism of cells, was very low, whereas significant yields were obtained in tissue cultures. The capacity of the red pulp abundant in pl.c. to produce antibodies in vitro was considerably superior to that of lymph follicles, rich in lymphocytes but devoid of pl.c. Antibody production was comparatively poor in tissue containing only transitional cells, reached a maximum when numerous immature pl.c. were present and receded when predominantly mature pl.c. were found. After intravenous injections the antigen accumulated in those places where pl.c. subsequently developed.

The conclusion is drawn that antibodies under the conditions of the experiments, are formed by cells of the R.E.S., passing through a chain of development, the final link of which is the mature pl.c.

The author takes this opportunity of thanking Professor F. Henschen, Professor G. Olin and Doctor S. Gard for their interest in this work and valuable criticism. The work has been facilitated by grants from the Foundation Therese and Johan Anderssons minne.
A Study of the Role of the Thymus and Spleen in the Formation of Antibodies in the Rabbit
Authors: Harris T. N. , Rhoads Jonathan , Stokes Joseph
Published: January 2023

The thymus did not play a demonstrable role in the formation of antibodies by the young rabbit, or in the retention of antibodies derived by the fetus from the maternal circulation. Only slight evidence of formation of antibodies in the spleen was shown following the subcutaneous injection of antigens. Following intravenous injection of antigens, however, high antibody-titers were demonstrated in splenic extracts. The failure of the thymus to form antibodies, which is in contrast with ecent and current observations on the lymph-nodes and spleen is discussed in erms of the architectural differences between the thymus and those organs.
Review Purified Animal Viruses
Authors: Beard J. W.
Published: January 2023

Progress in the purification of viruses has resulted, principally in the preceding decade, in an encouraging accumulation of knowledge of the chemical, physical and morphological characters of these agents. Though the initial successful studies in this field were made on bacteriophage and with agents responsible for animal diseases, widespread interest was given first to the findings with certain of the plant viruses. Work with the animal viruses under more complicated conditions for examination has continued, however, until, at the moment, there is a better understanding of some aspects of the characters of the animal viruses than of those of the agents causing disease in plants. Many general reviews (216, 87, 215, 222, 258) have been written of the findings with purified viruses, concerned in most instances with agents responsible for disease in plants. Smadel and Hoagland have reviewed (202) in detail the results with vaccinia virus and Pirie (168) has described the recent work with animal viruses.
The Antagonism of Coliform Bacteria Against Shigellae
Authors: Halbert Seymour P.
Published: January 2023

A total of 1,243 strains of coliform organisms, isolated by rectal culture from Latin-American children in South Texas, were tested for their antagonistic properties on solid medium against an arbitrarily chosen Shigella paradysenteriae Flexner type III (Z). Of these, 18.3 per cent possessed some antagonistic property. As indicated by identification tests with a random sample of these organisms, most were probably members of the Escherichia coli group. These strains were obtained from 147 individuals. A total of 37, or 25 per cent harbored one or more antagonistic coliform organisms. The antibacterial spectrum of these organisms is remarkably limited. Of a wide range of bacteria tested for susceptibility to sample coliform strains, only 38 of 58 strains of Shigella tested proved to be moderately or greatly affected, and 9 out of 15 strains of E. coli were shown to be moderately affected. Of the Shigella strains studied for susceptibility, a definite tendency was revealed toward a relationship between susceptibility and type specificity. The mechanism of the production of the zones of inhibition was shown to be due to antibiotic production in the instances tested. The zones of inhibition were not affected by rabbit and human blood or serum in concentrations of 5 to 25 per cent. A single case of acute diarrheal disease (of unknown etiology) was studied with reference to the antagonistic coliforms. During the course of the illness, there was a profound change in the coliform flora, in the direction of the development of organisms which showed a great degree of antagonism against Shigella Flexner type III (Z). This shift in the character of the flora paralleled the process of recovery. The possible significance of the findings is discussed.
Studies on Tularemia
Authors: Coriell Lewis L. , King Elizabeth O. , Smith Margaret G.
Published: January 2023

Clinical, laboratory and pathologic data on the course of tularemia in normal and vaccinated Macacus mulatta are presented. The disease in monkeys has many similarities to the disease in man. Vaccination did not protect immature monkeys against large infective doses and only partially protected young adult monkeys against small infective doses. An improved vaccine described by Foshay was the most effective of the four vaccines tested.
The Effect of Environmental Temperature Upon Resistance to Pneumococcal Infection Under Sulfadiazine Therapy, and Upon Body Temperature and Oxygen Consumption During Infection
Authors: Junge J. McBroom , Rosenthal S. M.
Published: January 2023

The resistance to pneumococcal infection under sulfadiazine therapy is significantly influenced by environmental temperature. The optimum is in the neighborhood of 26 C to 31 C, while markedly lowered therapeutic responses are observed at 18 C. Lowered responses also appear at 37 C.

In untreated mice with pneumococcus I infection no febrile response is observed during the course of the disease when the animals are maintained at room temperatures of 18 C or 31 C. As the infection progresses there occurs, at 18 C, a progressive fall in oxygen consumption and body temperature.
Precipitin Production in Chickens
Authors: Wolfe Harold R. , Dilks Eleanor
Published: January 2023

Ability to produce precipitin was studied in newly hatched chicks and chicks of various ages up to 12 weeks. The interfacial method was used. Newly hatched chicks gave low-titered antisera to bovine serum; slightly over one-half showed no precipitin with the dilutions (lowest 1:12.5) tried. There was a gradual increase in production-ability up to 4 weeks of age. The average titer given by the sera of 5-week-old chicks showed a remarkable increase over that of the 4-week-old ones. This increase could, in part, be attributed to the fact that almost all birds responded at 5 weeks of age. Chickens of 6 to 12 weeks of age gave titers similar to the 5-week-old ones indicating that serological “maturity” was reached at 5 weeks as far as precipitins against serum-proteins were concerned.
Studies on Inhibition of the Agents of Murine and Feline Pneumonitis by Penicillin
Authors: Eaton Monroe D. , Dozois Theodore F. , van Allen Alwine , Parish V. Lee , Schwalm Shirley
Published: January 2023

Prolongation of the survival time of chick embryos infected in the yolk sac with the agent of murine pneumonitis was obtained with doses of 2 to 20 Oxford units of penicillin per egg. An increase in the dose of 4 to 15 fold allowed survival of all embryos for 12 days after inoculation.

Inhibition of the development of the virus of feline pneumonitis was obtained with 20 to 2,000 units of penicillin per egg, or about 20 times as much as is required for comparable inhibition of the growth of the mouse pneumonitis virus.

Infections of the yolk sac caused by the agent of mouse pneumonitis were sterilized by penicillin in doses of 100 units given 24 hours after infection. For a similar complete virucidal effect on the cat pneumonitis virus, 5,000 units given three times at 2, 72, and 144 hours after infection were necessary.

When treatment was delayed the dose of penicillin required increased with the time after inoculation at which it was administered, but inhibitory and virucidal effects on the mouse pneumonitis virus were demonstrable with 5,000 units given 4 to 5 days after inoculation.

In vitro virucidal effects by crystalline penicillin G at a concentration of 2,000 units per cubic centimeter were not demonstrable. Impurities of unknown nature in crude penicillin were virucidal in vitro for the mouse pneumonitis virus.
Preparation and Properties of Purified Rickettsial Suspensions
Authors: Castaneda M. Ruiz
Published: January 2023

An improved method for the purification and concentration of typhus rickettsiae cultivated by the “lung method” is described. The material thus obtained may be used for various serological tests such as agglutination, complement fixation and opsonization. A suitable dilution of the stock suspensions may be used for the preparation of monovalent and bivalent vaccines which have been widely tested in the immunization of human beings. For emergency work an “oil protected” bivalent vaccine to be administered in a single dose is now being tested. The highly purified rickettsial suspensions have been successfully used to detect allergic reactions in typhus immune individuals with results which have indicated their value in epidemiological surveys.
Serological Studies on Infectious Mononucleosis and Other Conditions with Human Erythrocytes Modified by Newcastle Disease Virus
Authors: Evans Alfred S. , Curnen Edward C.
Published: January 2023

Serological reactions with human red blood cells modified by adsorption and elution of Newcastle disease virus (NDV) have been studied. Serum from some patients with infectious mononucleosis agglutinated such NDV-treated red cells in higher titer than serum from normal persons or from patients with non-infectious diseases. Similarly high titers were observed in the serum of some patients with other infectious diseases. Serum from rabbits immunized against Newcastle disease virus or against three other immunologically unrelated viruses agglutinated NDV-treated red cells in higher titer than normal rabbit serum or serum from a rabbit immunized against normal chick embryo tissue. Human serum as well as serum from rabbits immunized with viruses other than Newcastle disease virus, which agglutinated NDV-treated human red cells in high titer, failed to inhibit the agglutination of chicken red cells by Newcastle disease virus except for the serum of one patient which, however, failed to neutralize the virus. The capacity of both human and immune rabbit sera to agglutinate NDV-treated human red cells appeared to be unrelated either to the heterophile antibody of infectious mononucleosis or to the hypothetical agent of that disease.
Studies in Dysentery Vaccination
Authors: Cooper Merlin L. , Keller Helen M.
Published: January 2023

A study of sera from children convalescent from proven dysentery showed a wide range in the 50 per cent protective volumes, 0.0004 ml to 0.1 ml.

The agglutinative titers of these sera also varied widely, from 640 to 0.

The most protective sera were usually obtained from the older children.

All sera containing agglutinins were from the older children.
A Note on Enzyme-Purified Antitoxin and Anaphylaxis in Guinea Pigs
Authors: Christensen P. Agerholm , Kerrich J. E.
Published: January 2023

It has been confirmed that guinea pigs actively sensitized to pepsin-treated serum are sensitive to normal horse serum. It has been confirmed that guinea pigs sensitized to normal horse serum are less easily shocked by pepsin-treated antitoxin than by the unaltered antigen. It has been confirmed that guinea pigs sensitized to pepsin-treated antitoxin can be shocked by the same antigen. It has been shown that pepsin-treated antitoxin is more effective in eliciting anaphylactic shock in guinea pigs sensitized to pepsin-treated antitoxin than in guinea pigs sensitized to normal horse serum. This suggests that the antitoxin has acquired a new specificity, and the possibility of serum reactions in persons receiving enzyme-purified serum for the second time is emphasized. The validity of the results obtained has been assessed statistically.