bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional divergence of duplicated mosquito Toll and Spz compared to Drosophila
Authors: Saucereau Yoann , Marcaida Maria Jose , Gangloff Monique
Published: January 2023

Mosquitoes are vectors of many infectious diseases that constitute a risk to human health around the globe. Arthropod-borne viruses (arboviruses) such as Dengue and Zika viruses, are mainly transmitted by Aedes mosquito species, while plasmodium is spread by members of the Anopheles genus. The vectorial capacity of mosquito is based on a complex balance between the mosquito’s immune control and evasion mechanisms by the pathogen. The Toll signalling pathway is a key component of insect innate immunity that underwent duplication in mosquitoes compared to Drosophila melanogaster (Dm). Here we produced duplicated Spz isoforms and ectodomains of Toll1A and Toll5A in order to study binding specificity and signalling in Aedes aegypti (Aa). Surprisingly, Toll1A, the closest structural homolog to DmToll, did not bind to DmSpz, AaSpz1B or AaSpz1C, while Toll5A specifically bound to Spz1C. In Aag2 cells, however, DmSpz triggered gambicin production upon proteolytic processing, in contrast to mosquito Spz isoforms, which lead to a distinct set of antimicrobial peptides. Computational pairing of Toll and Spz failed to predict isoform and species-specificity, probably due to conformational changes upon ligand binding as observed by SAXS analysis of Toll5A-Spz1C complex. This study sheds light on the molecular basis of Toll and Spz neofunctionalization in the mosquito.
Significant upregulation of signaling and pro-inflammatory markers indicate adaptation for tolerance in bovine trypanosomosis
Authors: Morenikeji Olanrewaju , Metelski Jessica L , Thomas Bolaji
Published: January 2023

The initial immune response on exposure to trypanosomosis is a significant factor mitigating disease tolerance or susceptibility in cattle. CD14 is a signaling receptor involved in the activation of the TLR signaling pathway, contributing to the production of cytokines, including tumor necrosis factor-α (TNF-α). We had shown that CD14 expression in trypanotolerant cattle is an adaptation footprint, not found in susceptible animals. To further our analysis in delineating the role of TLR-4 and TNF-α genes in disease tolerance or susceptibility, we examined whole transcriptome and interactome of the two genes by elucidating their expression profiles in bovine tissues (liver, lungs, heart and kidney). Our analyses demonstrate a significant (p< 0.05) upregulation of TLR-4 and TNF-α in trypanotolerant cattle but not others. The upregulation of these genes in tolerant animals reflects a complete activation of the innate immune pathway, thereby hampering disease establishment, which is absent in the susceptible animals. This is contrary to reports in human studies, where the expression of these genes lead to disease chronicity, rather than tolerance. This indicates an evolutionary differentiation between cattle and human during speciation. Furthermore, we catalogued microRNA expression between disease groups via network analysis and identified 13 candidate microRNAs targeting CD14, TLR-4 and TNF-α, amongst others, which GO analysis reveal are involved in gene silencing, cellular protein modification process, etc. We conclude that the upregulation of these markers and the significant co-regulatory interactome is indicative of adaptation footprint in tolerant animal, helpful for bovine immune response against trypanosomiasis.
Immune and epigenetic regulation through histone-lysine N-methyltransferase Setdb2 during severe influenza virus infection
Authors: Ito Toshihiro , Imakita Natsuko , Hara Atsushi , Ouji-Sageshima Noriko , Kitabatake Masahiro
Published: January 2023

Influenza virus causes acute respiratory infections that are highly contagious, and leads to significant morbidity and mortality in humans and animals. Especially, the main severe pathogenesis following influenza virus infection are secondary bacterial pneumonia (SBP) and influenza-associated encephalopathy (IAE). Thus, a better understanding of the molecular mechanisms of these diseases is essential.

In our studies, microarray analysis demonstrated that influenza virus infected cells such as epithelial cells and macrophages upregulated SET domain, bifurcated 2 (Setdb2) expression following influenza virus infection via type-I IFN dependent manner. Setdb2 is a histone methyltransferase that methylates Lys-9 of histone H3 (H3K9), correlated with repression of transcription. Setdb2 expression in both influenza virus pneumonia and IAE models was significantly increased compared to control mice. Next, we investigated the role of Setdb2 in both SBP and IAE models. In SBP model, knocking down Setdb2 increased amphiregulin expression, which plays a critical role in tissue homeostasis of lungs and in decreased mortality of coinfection. In IAE model, the expression of Caveolin-1, one of the key proteins that correlate with protection of the blood-brain barrier, was significantly lower in brains from the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3K9 was correlated with repression of the Caveolin-1 promoter region.

These studies support the idea that an understanding of epigenetic change, especially via Setdb2, during influenza virus infection can provide mechanistic approaches for controlling and modifying the immune response in SBP and IAE.
Human rhinovirus and influenza A H1N1 monoinfection and co-infection induce both proinflammatory and anti-inflammatory responses in macrophages THP-1
Authors: Rosas-Taraco Adrian Geovanni , Martinez-Castilla Azalia M , Salado-Gamez Jaudiel H , Flores-Torres Armando S , Flores-Aldaba Kevin A , Torres-Lopez Ernesto , Salinas-Carmona Mario C
Published: January 2023

Macrophages play an important role in the innate immune response against several pathogens. Viral co-infections have been reported in humans; being human rhinovirus (hRV) and influenza A H1N1 virus (IAV) the most frequent co-infections. hRV and IAV monoinfection and co-infection models were developed in THP-1 macrophages. Viral detection and load were determined by QRT-PCR. Macrophage polarizations were performed using intracellular cytokines staining and flow cytometry; and ELISA was used to determine the cytokines levels. In monoinfection models, higher viral loads were found at 24h compared with 48h. On the other hand, viral load of IAV co-infection was lower compared with monoinfection when macrophages were infected first with hRV. The monoinfection with IAV at 48h and co-infection models induced higher percentages of TNF-a + macrophages when compared to the control (P<0.05). The percentages of IL-4+ macrophages were similar in all study groups (P>0.05). IL-10+ macrophages were significantly increased in hRV monoinfection model at 48h and in the co-infection models compared with control (P<0.05). A high percentage of macrophages that co-expressed IL-4+ and IL-10+ were detected in the IAV monoinfection at 48h and co-infection models compared with control group (P<0.05). Monoinfection models induced high levels of TNF-a at 24h compared with control (P<0.05). IL-4 levels were similar in all study groups (P>0.05). IL-10 levels were elevated in monoinfection models, as well as in hRV/IAV co-infection when compared to control (P<0.05). Our results suggest the presence of proinflammatory and anti-inflammatory responses during monoinfection and co-infection models of hRV and IAV.
LAG-3 marks effector to regulatory evolution of Th1 immunity in influenza
Authors: Dutta Avijit , Hung Chen-Yiu , Hsieh Yu-Chia , Chang Chia-Shiang , Chen Ting-An , Huang Yu-Lin , Lin Yung-Chang , Chen Tse-Ching , Lin Chun-Yen , Huang Ching-Tai
Published: January 2023

Naïve CD4+ T cells respond in influenza with T-bet expression, a transcription factor up-regulated with Th1 commitment. We report concomitant LAG-3 expression on these Th1 committed cells with evolution into regulatory T cells. LAG-3 expression increases with activation as revealed by CFSE cell division study. Cells with moderate LAG-3 expression produce IFN-γ and contribute to inflammation and disease. They no longer produce IFN-γ with higher LAG-3 expression upon further activation. High LAG-3 cells suppress and decouple effector function from the preserved proliferation of CD8+ T cells. They restrain inflammation with facilitated viral clearance and ameliorate the disease of severe influenza. Foxp-3+CD4+ T cells suppress both effector and proliferative responses with impaired viral clearance and they are less potent in disease amelioration. Principal component analysis of genome-wide expression further confirmed the stepwise evolution from effector to regulatory T cells. Regulatory genes are up-regulated progressively from LAG-3Neg to LAG-3Med and to LAG-3High cells.
Mechanism of T cell mediated hemorrhagic disease during LCMV infection
Authors: Luna Evelyn , McAfee Megan , Carmen Joshua , Canter Hannah , Ahmed Rafi , Greenberg Philip D , Blattman Joseph N
Published: January 2023

T cells are essential in controlling and clearing viral pathogens, but they also have the potential to induce immunopathology. We have previously shown that this balance between protection and pathology is dependent on the number of virus-specific T cells. Specifically, intermediate numbers of CD8 T cells result in lethal hemorrhagic disease, while lower doses result in exhaustion, and higher doses in viral clearance. Increasing the number of virus-specific CD4 T cells also leads to lethal hemorrhagic disease, however the mechanism by which T cells mediate this pathology remains unclear. Using lymphocytic choriomeningitis virus (LCMV) and an in vivo adoptive transfer mouse model, we found that lethal pathology induced by CD8 T cells is dependent on tumor necrosis factor (TNF). The absence of TNF signaling abrogates pathology without impeding viral clearance. Interestingly, CD4 T cell induced pathology, while dependent on CD8 T cells, still occurs in the absence of TNF. Furthermore, IL-2 produced by CD4 T cells modulates CD8 T cell responses to generate hemorrhagic disease that is TNF-dependent. Our findings show that TNF plays a significant role in T cell mediated hemorrhagic disease, and further implies that CD4 T cells modulate CD8 T cells to follow a different mechanism of pathology in the absence of this potent pro-inflammatory cytokine.
Memory-like NK responses to Zika virus infection
Authors: Kujur Weshely , Murillo Oscar , Mulik Sachin
Published: January 2023

The formation of memory is a hallmark feature of adaptive immune cells such as T and B lymphocytes. Natural killer cells (NK), though part of the innate immunity, have also been shown to undergo memory program to haptens, cytomegalovirus and other pathogens. We investigated NK response after Zika virus infection in mice. The activation of NK cells was evident early after infection, with increased frequencies of CD27+KLRG1+ NK cells producing higher amount of IFN-γ and perforin. These responses were normalized a month post infection. However, investigating CD27+ NK cells a month post Zika infection led to identification of memory like phenotype in these cells. The CD27+ NK subset (day 37 post infection) demonstrated greater therapeutic potential than CD27− NK subset or naive CD27+ NK cells when adoptively transferred to Zika infected interferon receptor deficient mice. The cell trace violet labeled CD27+ NK cells (day 37 post infection) when transferred to recipient mice robustly proliferated after Zika challenge. Moreover, the response of these memory-like CD27+ NK cells were antigen specific as these cells failed to proliferate in the recipient mice after bacterial challenge. Memory-like CD27+ NK cells persisted, had lesser reactive oxygen species, healthy mitochondria and lesser apoptotic features. This study reveals memory-like NK responses to Zika virus infection. It remains to be seen if specific NK receptor or cytokines are involved in generation of memory-like NK responses to Zika infection.
Studies of the Flocculation-Reaction Time in the Course of Immunization and the Quantitative and Qualitative Changes of the Proteins
Authors: Berthelsen Knud C.
Published: January 2023

A consistent increase in the flocculation-reaction time has been found during the immunization period of horses used for diphtheria antitoxin production. It is suggested that the speed of reaction is an expression of the interfacial state of the antitoxic-protein-molecule complex.

A study was made of various quantitative and qualitative characteristics of antitoxic sera as related to the flocculation reaction.

Nine horses were immunized with infusion-free toxin, by both a slow and a rapid immunization technic. Three horses were immunized with purified infusion-free toxin and three horses with a routine toxin containing meat infusion. During the immunization period the horses were followed for any biochemical changes in order to determine, if possible, the existence of any relationship between the flocculation-reaction time and quantitative differences of one or more of the physicochemical constants of sera.

A technic was developed for determination of the surface tension of plasma in order to exclude the errors present when serum is used.
The Distribution of Electrolytes in Serum During Immunization
Authors: Berthelsen Knud C. , Murdick Philip P.
Published: January 2023

At progressive stages of immunization before and after toxin injection the diffusible calcium, non-diffusible calcium, and total base have been estimated.

At weekly intervals during the course of immunization the diffusible and non-diffusible phosphorus has been determined.

The ultrafiltration technic has been employed in order to separate the diffusible from the non-diffusible constituents.
Random Mating and Blood Groups
Authors: Jenkins R. L.
Published: January 2023

A criterion on internal consistency of blood groups is here presented for application to large bodies of data in the study of blood groups from an anthropological standpoint. The failure of data to meet this criterion is to be interpreted as evidence either of selective mating with regard to blood groups or of errors in the technique of grouping and indicates that the data is unsuitable for the application of the technique of Snyder for calculating p, q, and r, the absolute frequencies of the triple allelomorph gens among the population.
On Immune Isoagglutinins in Rabbits
Authors: Levine Philip , Landsteiner K.
Published: January 2023

In this paper several additional observations are recorded on the production and properties of immune isoagglutinins in rabbits.

Contributions to this subject not covered in our first article (1) and in the papers by Fischer and Klinkhardt (2) are the following. Ascoli (3) describes in two among numerous cases the formation of isolysins and isoagglutinins after injection of rabbits with their own blood hemolyzed by water (cf. Hulot and Ramond (4)). These results could not be duplicated by Kraus and Ludwig (5). Robertson and Rous (6) observed the development of isoagglutinins and autoagglutinins as the result of transfusing rabbits with the blood of other rabbits. A report of normal isohemagglutinins in rabbits was recently made by Gara (7).

An extensive study on isoagglutinins in rabbits was made by Fischer and Klinkhardt. Their experiments, made mostly after serological selection of donors and recipients, resulted in the demonstration of two sorts of agglutinins, determining two agglutinable properties.
Studies in Anaphylaxis in the Rabbit
Authors: Grove Ella F.
Published: January 2023

Of 20 rabbits that received two injections of fowl corpuscles at an interval of five days, all were found to be maximally sensitive upon the intravenous test injection seven days after the second sensitizing injection. All of the sera of these sensitized rabbits agglutinated the corpuscles used for injection and the agglutinins were only slightly reduced by mixing the serum with relatively large quantities of the water-soluble corpuscular substances. Rabbits sensitized with two injections of whole fowl corpuscles are not necessarily sensitive to the water-soluble corpuscular substances, and are not desensitized by large quantities of the latter to the subsequent injection of whole corpuscles. Antisera prepared against goose corpuscles (which are said to lack the Forssman antigen) are toxic for normal guinea pigs; this toxicity can be removed by absorption with guinea pig kidney. Anti-goose corpuscle serum rendered non-toxic by absorption with guinea pig kidney tissue and injected intravenously into normal guinea pigs renders these animals hypersusceptible to the injection of whole goose corpuscles one hour later. The subcutaneous reinjection of fowl corpuscles almost always results in the development of the Arthus necrosis.
Natural Resistance to Disease in the Chicken
Authors: Lambert W. V.
Published: January 2023

Extensive bacteriological examination of the organs of 61 breeding birds, all survivors of a fowl typhoid infection, showed 21.3 per cent of them to be carriers of S. gallinarum. The ovary was the most frequent seat of localization of the bacterium in the females. Only 1 of 7 males examined proved to be a carrier. Chicks hatching from the carrier hens proved slightly, but not significantly, less resistant than those from non-carrier hens. The mortality among 129 chicks from carrier hens was 44.2 per cent and among 366 chicks from non-carrier hens 40.2 per cent. The non-carrier hens were those from which the organism was not isolated.

Data secured from bacteriologic examination of a small number of chicks killed at various intervals after infection suggest that chicks from the selected population are more refractory to the fowl typhoid organism than are chicks from an unselected population. Agglutination tests on the blood serum of these chicks indicate that the young chick lacks the ability to develop agglutinins of high titer, if at all.
Studies in the Variability of Tubercle Bacilli
Authors: Rice Christine E. , Reed G. B.
Published: January 2023

The S type of various strains of acid-fast bacteria, Mycob. leprae and human, bovine and avian tubercle bacilli have been found to contain antigenic substances not present in the R type of the same strain, dissociation apparently being accompanied by a considerable loss in antigenic complexity.

Immune sera prepared against such S organisms contain certain antibodies reacting with extracts of the homologous S organisms but not with the homologous R type, other antibodies reacting with both S and R of the same species and a third type of antibody detected by antigens prepared from the other species of acid-fast bacteria, that is a group antibody.

Antisera prepared against R organisms on the other hand appear to lack the S-specific antibody which is found in S antiserum but contain a much higher proportion of antibodies reacting with extracts prepared from other acid-fast species. The possible chemical nature of the various antigenic substances has been briefly discussed.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R.
Published: January 2023

Reference has been made in the preceding article (1) to the error in using the mean percentage mortality as typifying the underlying probability for an event, such as death, in a population, unless the deviation of the mortalities by an authentic subdivision lies within the errors of random sampling of that of a binomial, or Bernouillan, distribution.

In the experiments heretofore reported, if heredity has played a major part in determining the resistance of an animal, it follows that the behavior to an infection of the offspring from any mating will be determined in the main by the interaction of the factors received from the respective parents. Under such conditions, the litters constitute the logical subsets into which the population should be divided for an analysis of the type of distribution.

A method for such an analysis has been previously described by the author (2, 3). A much more complete exposition has been presented by Snedecor (4).
Chemical and Immunological Studies of the Pneumococcus
Authors: Wadsworth Augustus , Brown Rachel
Published: January 2023

From the bacterial cells of types I, II, III and of an atypical variant of type I pneumococci, substances of carbohydrate nature have been prepared. They all contained phosphorus and nitrogen. They differed in their precipitative activity. The fractions from the virulent organisms of the three types reacted in high dilution with the homologous antisera only, while that from the atypical type I pneumococci reacted with type I antiserum in a very low dilution and with types II and III in high dilution. They gave rise to skin reactions in immunized but not in normal rabbits. The response was not highly specific. They induced purpura in mice. This activity of the type I cellular carbohydrate, which further distinguished it from the soluble specific substance, was not destroyed when the cellular substance was heated in n/100 sodium hydroxide or hydrochloric acid, at 100°C. for thirty minutes or was autoclaved in n/100 sodium hydroxide, at 120°C. for twenty minutes. It was inhibited by type I antipneumococcus rabbit serum and intensified by immune horse serum. The type I material could be separated by acid precipitation into two fractions which differed in their precipitative activity and in their ability to induce purpura in mice. The type I cellular carbohydrate precipitated from two to three times as much nitrogen from immune serum as did the soluble specific substance. When injected through the trachea into the rabbit lung, the type I cellular carbohydrate gave rise to a marked diffuse inflammatory reaction. The cellular carbohydrates of all three types induced specific anaphylactic shock in sensitized guinea pigs. The cellular carbohydrate from the type I attenuated strain did not induce this phenomenon in guinea pigs sensitized with any one of the three types of antisera.
A Note on the Fractionation of Antimeningococcus Serum
Authors: Murdick Philip P. , Cohen Sophia M.
Published: January 2023

Experiments were undertaken to determine the protein fraction or fractions of antimeningococcus serum with which are associated the agglutinative and precipitative activities and also the neutralizing activity for the toxic substance of the meningococcus which induces the phenomenon of local skin reactivity.

In the method for the concentration of antimeningococcus serum described in a paper by Neal and others (1) concentration of the agglutinative activity was obtained by separation of a water-insoluble globulin after partial removal of euglobulin by saturation of the serum with sodium chloride. Similar results have been obtained in this laboratory with Banzhaf's method (1). It was noted, however, with certain sera, that a lower degree of concentration of potency for group II strains was obtained than for strains of groups I and III. With one serum particularly, potency for group II strains, as determined by the precipitation reaction, was adversely affected by concentration.
Tissue Culture Studies on the Relation of the Tuberculin Reaction to Anaphylaxis and the Arthus Phenomenon
Authors: Aronson Joseph D.
Published: January 2023

The growth and migration of cells in explants from the spleen and bone marrow of tuberculous guinea pigs are inhibited by the addition of tuberculin; those explanted from non-tuberculous guinea pigs sensitized by a single injection of horse serum are not inhibited by horse serum.

Migration and growth in similar explants from tuberculous guinea pigs sensitized to horse serum are not inhibited by the addition of horse serum; it was found that they are, on the other hand, inhibited by tuberculin.

When the Arthus phenomenon was elicited by injections of horse serum into normal and tuberculous guinea pigs the tissue cultures were unaffected by the addition of the serum.

These tissue-culture experiments suggest that the mechanism underlying the tuberculin reaction is different from the mechanisms of anaphylaxis and the Arthus phenomenon.
Blood Grouping Among the “Blackfeet” and “Blood” Tribes of American Indians
Authors: Matson G. A. , Schrader H. F.
Published: January 2023

Although various tribes of American Indians have consistently been reported as belonging primarily to group O, the Blackfeet and Blood tribes appear to be an exception, showing as high a percentage of group A as other tribes show of group O. This may be seen by comparing tables 2 and 3, with 1 and 4.

These results suggest the necessity for reconsidering the origin of the American Indian.
Complement Fixation Test in Carcinoma
Authors: Saphir William , Hirschberg Nell
Published: January 2023

Summary and Conclusions

The complement fixation test in carcinoma has been studied in 27 sera of cancer patients and 82 control sera. The tests were positive in 77.7 per cent of the 27 sera from the cancer patients, and of the 82 control sera only one, from a patient with lobar pneumonia, gave a positive reaction. The authors are of the opinion that the reaction is of a physical-chemical nature due to the influence of the antigen upon the serum globulins rather than a specific antigen-antibody reaction. The clinical value of the reaction awaits further observation after refinement and a better understanding of the nature and the limitations of the test.
Absorption Spectra of the Carbohydrates of the Pneumococcus
Authors: Wadsworth Augustus , Crowe M. O'L. , Smith L. A.
Published: January 2023

The bacterial carbohydrates of the pneumococcus differ in their serologic and immunologic action, their chemical composition, some of their physicochemical properties, such as optical rotation and ionization, and according to their source. Those from typical cultures of the various types are distinctive in character and differ from preparations obtained from atypical, attenuated strains. With, possibly, the exception of the type III soluble specific substance, these materials have not been obtained in the chemically pure state. Additional data for purposes of comparison are essential to the further study of the relative significance of these different preparations in the antigenic and pathologic activities of the pneumococcus. Hence, this quantitative spectrophotometric study of preparations at different stages of purification was undertaken, and the preliminary work is here reported.

The preparations selected were, as far as possible, those which were used in chemical and immunological studies previously reported from this laboratory (1).
The Agglutinogens M and N of Landsteiner and Levine
Authors: Wiener Alexander S. , Zinsher Rebecca , Selkowe Joseph
Published: January 2023

Summary and Discussion

The results of experiments with the technic of typing for M and N have been presented and discussed. The most important requirement for accurate results is the proper potent reagents. For the preparation of potent sera, prolonged and intensive immunization is necessary, and when preparing anti-M sera the desired effect is often obtained by giving the rabbits a long rest period (one or more months) followed by an additional brief course of injections. The preparation of the anti-N testing fluid from the immune serum offers more difficulty than the preparation of anti-M fluids, because of the greater tendency to non-specific absorption with the former. However, there is usually no difficulty in preparing fluids with a titer of at least 10 and 20, and with reagents of such potency accurate results are possible. The majority of bloods of the heterozygous type are less sensitive to agglutination than bloods of the corresponding homozygous types, so that it is important to include an adequate number of control bloods of each of the three types M, N, and MN in every experiment. Other factors which must be taken into account are the possible presence of interfering agglutinins, which can be removed by suitable absorption experiments, and the effect of variations of the concentration of the suspension, the age of the blood, and temperature on the reactions.

In medicolegal cases, absolute reliance should not be placed on any single set of reagents, and, of course, for such work adequate experience is of prime importance.
The Concentration of Antistreptococcus Plasmas of Different Antitoxic Potencies
Authors: Murdick Philip P. , Hendry Jessie L.
Published: January 2023

A method is described for the concentration of antistreptococcus plasma.

The results obtained with this procedure in the concentration of a number of lots of plasma ranging in antitoxic potency from 100 to 1000 units per cubic centimeter are recorded. The average unit concentration is 5 with a 24-per-cent loss of antitoxin.
The Bactericidal Action of Whole Blood, with a New Technique for Its Determination
Authors: Heist George D. , Solis-Cohen Solomon , Solis-Cohen Myer
Published: January 2023

That the serum of a pigeon does not differ in its action upon pneumococci from the serum of a mouse or rabbit would appear from our experiments as well as from those of previous investigators.

We have found, however, that if small numbers of living pneumococci are seeded, by a suitable method, in pigeon's blood before it coagulates the penumococci fail to multiply. On the contrary if pneumococci are seeded in mouse's or rabbit's blood before it coagulates the pneumococci grow with great vigor. The evidence points to the presence in the uncoagulated blood of the pigeon of a bactericidal factor which is absent from the blood of the mouse or rabbit.

Fresh defibrinated blood of both immune and susceptible species is an excellent culture medium for the pneumococcus, which shows that the bactericidal factor disappears during the process of coagulation.

Pneumococci fail to multiply in the blood of a rabbit which has been suitably inoculated with killed pneumococci, the reaction being specific to type.

The blood of a man that has recovered from lobar pneumonia prevents the growth of pneumococci belonging to the type which caused his disease.

The globoid bodies of poliomyelitis grow readily in uncoagulated human blood. They fail to grow when seeded in uncoagulated rabbit blood.

Many of the non-pathogenic bacteria usually met with as contaminations in bacteriological work, as for instance the B. subtilis, fail to grow when seeded in uncoagulated blood.

The tentative hypothesis advanced to cover the facts observed is that when small numbers of bacteria are seeded in blood before it has had time to coagulate only those bacteria grow and multiply which are pathogenic for the animal from which the blood is taken.
Active Immunization against Poliomyelitis. A Comparative Study
Authors: Kramer S. D.
Published: January 2023

Summary and Conclusions

In this, the first part of our comparative study of active immunizing agents, efforts were made employing the technique recommended by Brodie to duplicate the responses obtained by him in the experimental animal and in children, with 5 cc. of a 10 per cent suspension of virus (corresponding to 0.5 gram of cord) rendered non-infective with 0.1 per cent formalin. Brodie states that he has produced an immunity sufficiently great to compare favorably with the immunity resulting from a frank attack of the experimental disease with residual paralysis (15).

Such response was not apparent in our experiments. The serums of only two of the animals neutralized 0.1 cc. of a 5 per cent suspension of virus, and both of these animals succumbed to 0.01 cc. of virus. Essentially identical results were obtained in the series of animals treated with 10 cc. formalized material, corresponding to 1 gram of poliomyelitis cord. Of the three animals that gave some evidence of neutralizing substance in their blood, 2 succumbed to 0.01 cc. of a 5 per cent suspension of virus (or one-tenth of the minimal constant infective dose) and the third died of intercurrent infection.

A group of 14 non-immune children were inoculated with 5 cc. of formalized virus supplied and administered in the manner recommended by Brodie. These children were again bled one to two months later and their serums tested for the presence of neutralizing substance. Seven of the 14 children, or 50 per cent, had developed neutralizing substance in their serums at the time of the second bleeding. A control group of 17 non-immune children (as indicated by the absence of neutralizing substance in their serums at the time of the first bleeding) were again bled from one to three months later. Seven of these 17 children, or approximately 41 per cent, had developed neutralizing substance in their serums. A difference of 9 per cent in favor of the vaccinated group does not appear significant.
Vitamin C and Anaphylactic Shock in Guinea Pigs
Authors: Solomonica Bruno
Published: January 2023

Introduction. The following experiments were suggested by an earlier study (1) of the effect of endocrinal preparations on anaphylactic shock in guinea pigs. Special attention had been paid to the effect of prolonged administration of anterior pituitary extract previous to and following sensitization over specified lengths of time. In the conclusions of that article it was emphasized first that administration of this glandular preparation was more efficacious in preventing anaphylactic shock if administered prior to sensitization than after the animal had been sensitized; and secondly, that there seemed to be a correlation between the state of the endocrinal system due to such treatment and the amount of protection that guinea pigs sensitized with horse-serum showed against anaphylactic shock. The question was left open whether this protection was due directly to the anterior pituitary extract or indirectly to the state of the adrenal, thyroid, and sexual glands which, as it is known, undergo changes after administration of an alkaline extract of the anterior pituitary gland.
Studies on Barbiturates
Authors: Mollari Mario , Randall William A. , Koppanyi Theodore
Published: January 2023

Large amounts of sodium barbital or sodium phenobarbital inhibit complement hemolysis, and prevent the coagulation of citrated plasma and of whole blood.

Relatively small amounts of sodium barbital or sodium phenobarbital have no effect on the complement or on the coagulation of plasma and whole blood.

Barbital and phenobarbital even in saturated solutions have no effect on the complement or on the coagulation of plasma and whole blood.

The injection of large amounts of sodium barbital into an animal will neither change the complement activity of its blood serum, nor alter the coagulation of the plasma or whole blood.

Sodium carbonate in amounts sufficient to reach the hydrogen ion concentration existing in the mixtures after the addition of the sodium salts of the barbiturates produces similar effects on the complement activity of the serum, on the coagulation of citrated plasma, and of whole blood.

The inhibition of complement hemolysis, the prevention of coagulation of heated citrated plasma and of whole blood is due to the alkalinity of the medium.
Hemolytic Streptococcus Toxins and Antitoxins
Authors: Rane Leo , Wyman Louise
Published: January 2023

Summary and Conclusions

A flocculative test for the titration of hemolytic-streptococcal toxins and antitoxins has been developed which is comparable to the Ramon method for titrating diphtherial toxins and antitoxins. The technic employed in flocculation is essentially that of the Ramon test.

Concentrated toxins, prepared by the method described, are preferable to crude toxins because they flocculate with greater rapidity.

One unit of antitoxin will combine in the flocculative reaction with 60,000 STD of toxin instead of with the 50 STD to be expected on the basis of the definition of an in vivo unit of antitoxin. This relationship has been true of all toxins tested except those modified by formalin.

Streptococcal toxins and antitoxins display individual variations in their flocculating time and are influenced by the same factors as diphtherial toxins and antitoxins.

The flocculating antibody is produced in horses in amounts which parallel the antibody produced against the erythrogenic toxin. It is at least possible that the two antibodies are identical. The average of the in vivo/in vitro ratios was found to be 0.963. The correlation-coefficient of the values obtained by the flocculative test and by the intracutaneous test in rabbits was 0.947 ± 0.023.

The Dochez NY 5 strain of hemolytic streptococcus was used as the basis for this study although flocculation was produced with other strains of hemolytic streptococci and their homologous antitoxins. The question of multiplicity of streptococcus-toxins is not dealt with in this report.
Chemical and Immunological Studies of the Pneumococcus
Authors: Wadsworth Augustus , Brown Rachel
Published: January 2023

By ultrafiltration, pneumococcus culture filtrates of types I, II, III, and a nonvirulent atypical strain (I) were conveniently concentrated a hundred-fold. At the same time, from 97.4 to 99.3 per cent of the nitrogen was eliminated. Subsequently, by repeated fractional precipitations with alcohol, type-specific and species-specific polysaccharides were obtained in good yield and in a relatively high state of purification. These type-specific substances possessed greater activity in precipitation with immune serum than those prepared by other methods, and the type I regularly induced immunity in mice.
The Response of Infants to Inoculation with Type I Pneumococcus Carbohydrate
Authors: Davies John A. V.
Published: January 2023

Of a group of fifteen infants from two to fifteen months of age inoculated subcutaneously and intracutaneously with type I pneumococcus carbohydrate, only one responded, during the period of observation, with demonstrable humoral type I pneumococcic antibody.
Studies on Serum Fractions
Authors: Ando K. , Manako K. , Kee R. , Takeda S.
Published: January 2023

Diphtheric antitoxin is precipitable by the precipitating serum prepared with the floccules of diphtheric toxoid-antitoxin (P.V.At.), whereas pneumococcal antibody is precipitated by the precipitating serum prepared with specific precipitates of pneumococcal SSS (P.V.Ab.) in their optimal proportions and also in the range of excessive precipitin. The former precipitating serum absorbs also antipneumococcal antibody from antipneumococcal horse serum, but it is only in the range of the mixtures containing far less antipneumococcal serum than the quantity present in the optimal proportion. The latter precipitating serum absorbs also antitoxin from antidiphtheric horse serum, but this absorption occurs only in the secondary zone and not in the primary or main zone.
Comparative Titrations of Antimeningococcus Sera Produced with Living Cells and with Broth Filtrates
Authors: Kirkbride Mary B. , Cohen Sophia M.
Published: January 2023

In an attempt to demonstrate differences that might be present in antibacterial and antitoxic sera, horses were immunized over a period of months with toxic filtrates of broth cultures or with toxic filtrates and living cells. The sera thus produced were tested by various laboratory methods in comparison with standard therapeutic sera produced by the immunization of horses with living cells injected intravenously, and with meningococcus antitoxin prepared elsewhere.

None of the different methods employed, including intracutaneous tests on persons, could be considered satisfactory as a means of titrating antitoxic potency. The lack of a practical and dependable method of standardization of the antitoxic serum was apparent.

Nevertheless, it was possible to draw certain definite conclusions from the sum of the trends in the various tests of antitoxic potency: Qualitative differences between the antitoxic and the antibacterial sera were not evident by the methods employed.Marked antitoxic potency was not demonstrable in either type of serum.The slight or moderate neutralizing activity which was indicated in the sera in one or another of the tests, was usually but not always more pronounced in the antitoxic as compared with the antibacterial serum. No striking quantitative difference between the samples of antitoxin and the standard therapeutic material could, however, be said to obtain.

Definite quantitative differences in the agglutinative and precipitative activities of the sera and in their protective action for mice against virulent living cultures were established. The standard sera were much the more potent in these respects.

Separation and titration of the water-soluble and water-insoluble globulin fractions of the sera produced with toxic filtrates and with living cells or cells and filtrate indicated a different distribution of the active substance in the sera. The significance of this is not clear, especially since concentration failed to enhance markedly the antitoxic potency.

The data accumulated from this investigation do not warrant the substitution of toxic filtrates for the living cultures now used for the production of therapeutic serum.
Studies in Experimental Hypersensitiveness in the Rhesus Monkey
Authors: Walzer Matthew , Gray Irving , Straus Henry W. , Livingston Saul
Published: January 2023

In recent studies by Walzer, Sherman, Feldman, and Kaplan (1, 2) it was demonstrated that the mucous membranes of the eyes and of the nose in humans could be passively sensitized at will with sera containing atopic reagins. Gray and Walzer (3) have shown that the mucous membranes of the rectum in man are also subject to passive local sensitization with such sera. Similar studies in human beings on the mucous membranes of organs in the thorax and abdomen were naturally limited because of the inaccessibility of such tissues.

Recently, Straus (4) demonstrated conclusively that the skin of the Macacus rhesus monkey could be passively sensitized with human atopic antibodies. This finding suggested the use of the rhesus monkey for studying passive sensitization of those organs which could not be experimentally explored in human subjects. The present communication is a brief preliminary report of the results of such experiments in passive sensitization performed on some of the abdominal organs in the rhesus monkey.
A Constituent of Peptone Broth as a Cause of Cross Reactions with Antisera Prepared against Group C (Lancefield) Hemolytic Streptococci
Authors: Bliss Eleanor A.
Published: January 2023

Summary and Conclusions

A heterologous precipitative reaction with group C streptococcal antisera has been described. This reaction, first noted when HCl-extracts of hemolytic streptococci belonging to other Lancefield groups were tested against group C antisera, has been shown to occur also with extracts of extraneous microörganisms such as B. coli, with “extracts” of sterile Neo-peptone and Bacto-peptone broth, and with saline solutions of Neo-peptone. Immunization of rabbits with strains belonging to other groups of hemolytic streptococci has not, in our hands, resulted in the formation of similar heterologous antibodies. Sterile Neopeptone broth was equally inert. Washing of the bacterial suspensions from which the HCl-extracts were prepared abolished the reaction. There was also no reaction when the organisms for the extracts were grown in peptone-free broth. The use of washed group C vaccines did not interfere with the production of the heterologous antibody in rabbits. The heterologous reaction appears to depend upon two things—the use of group C streptococci for antibody production and the presence of peptone, or some constituent of peptone, in the HCl-extracts.
Serological Studies of the Reptilia
Authors: Bond Glenn C.
Published: January 2023

This paper had for its primary purpose, a study of the hemagglutinins and hemagglutinogens of snake blood and their similarity to human hemagglutinins and hemagglutinogens.

By an appropriate technic it was found that isohemagglutination did not occur with the samples of snake blood examined. Heterohemagglutination and heterohemolysis did occur between genera and between families of the Serpentes. This heterohemagglutination showed no correlation to zoological grouping.

From a comparative study of snake and human bloods it was observed that the snake erythrocytes examined did not contain agglutinogens for human Alpha and Beta agglutinins. Snake serum, however, may or may not contain agglutinins which act similarly to the Alpha and Beta agglutinins of human serum. In addition to these 2 specifically acting agglutinins, it was found that some snake sera contain an agglutinin which can be absorbed by human cells of any group. The specific agglutinins of snake serum and the Alpha and Beta agglutinins of human sera are equally thermolabile.

Appropriately selected and absorbed snake sera can be used to determine the blood grouping of unknown human cells.
Anaphylaxis in the Rhesus Monkey
Authors: Kopeloff Lenore M. , Kopeloff Nicholas
Published: January 2023

Severe and fatal anaphylaxis was produced in monkeys by means of egg-white. Repeated injections proved more effective for sensitization than a single dose of antigen. Precipitins were found after multiple doses but not after a single sensitizing injection. The Arthus reaction was demonstrable when specific precipitins were present. Passive transfer to monkeys was successful with rabbit and monkey anti-egg-white serums and also rabbit anti-crystalline ovalbumin serum. An interval of one-half hour was as effective as forty-eight hours. Transfer to guinea pigs was also demonstrated with monkey serums which contained precipitins, when followed forty-eight hours later by egg-white. Attempts to passively sensitize local skin sites with the above-mentioned antiserums proved negative when various intervals were employed. Dilution, or filtration of egg-white through paper, diminished its capacity for sensitization or shock Crystalline ovalbumin as well as whole egg-white failed to produce precipitins to crystalline ovalbumin in the monkey. This may account for its relative ineffectiveness for sensitization and shock. However crystalline ovalbumin caused shock in monkeys passively sensitized with rabbit anti-crystalline ovalbumin serum. Actively sensitized monkeys which had recovered from anaphylactic shock following the administration of egg-white were shown to be desensitized when tested on the following day. The specificity of the above reactions was established by control tests with horse serum. The Schultz-Dale test for smooth muscle contraction proved negative on uterine and intestinal strips excised from monkeys actively and passively sensitized. Fatal anaphylaxis usually occurred within six minutes after the shocking dose of egg-white and was usually preceded by respiratory difficulty, unconsciousness and collapse. Gross examination of the internal organs showed occasional emphysema of the lungs with petechial hemorrhages. Following shock, the blood platelets were reduced to approximately one-third or less of their original number, and the clotting time was appreciably delayed.
Sensitization and Antibody Formation in Monkeys Injected with Tubercle Bacilli in Paraffin Oil
Authors: Casals J. , Freund Jules
Published: January 2023

Coulaud (1) has shown that the addition of paraffin to heat-killed tubercle bacilli promotes the sensitization of rabbits to tuberculin. Saenz (2) found that the solid paraffin could be replaced by liquid paraffin oil. He produced very intense and lasting sensitization in guinea pigs by subcutaneous or intramuscular injections of 1 cubic centimeter of paraffin oil containing a large amount of heat-killed and dried tubercle bacilli. Freund, Casals and Hosmer (3) observed that, both in the guinea pig and the rabbit, the addition of small amounts of paraffin oil to heat-killed tubercle bacilli augmented not only sensitization but also the formation of complement-fixing antibodies.

The purpose of the present work was to determine whether paraffin oil containing heat-killed tubercle bacilli effectively sensitizes Macacus rhesus monkeys, a species said to be lacking in the capacity to develop cutaneous sensitization to tuberculin.