bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of IL7R α in Xenopus tropicalis: implications for the evolution of cytokine signaling pathways
Authors: Appasamy Pierette M , Lambert Lisa A. , Sammons John C. , Daskalova Kristina G.
Published: January 2023

Signaling through the IL7 receptor is essential for development of B and T cells in humans and mice, as evidenced by the SCID-like phenotype seen in the absence of IL7/IL7 receptor signaling. The IL7R signaling system is active in lower vertebrates but has not previously been examined in Xenopus frogs. The IL7R is a heterodimer comprised of the IL7R α chain and the “common” γ chain that is shared by other IL2 family cytokines that utilize the JAK-STAT pathway. We have recently cloned the IL7R α cDNA from Xenopus tropicalis. Comparison of the predicted amino acid sequence of the Xenopus IL7R α indicates closest homology with the zebrafish IL7R α, and significant homology with other characterized IL7R α including those from humans, mice, chickens, alligators, primitive caecilians, green sea turtles, and anole lizards. Analysis of the predicted amino acid sequence indicates an intact WSXWS motif (common to all IL7R family members). The Box 1 motif, normally required for JAK interaction, has an asparagine replacing aspartic acid (similar variations are found in the zebrafish and anole lizard IL7R α sequences). There are at least five potential N glycosylation sites. There is a 16 amino acid insert unique to the Xenopus sequence that is not found in the reported IL7R α sequence of any other animal that we have examined. Our attempts to identify an IL-7 gene in the Xenopus genome have been unfruitful. Synteny analysis indicate there is no gene with homology to IL-7 at the expected position in the Xenopus genome. Interestingly, we have identified a transposon in place of the IL-7 gene at the expected position. The distribution of IL7R α in various organs of X. tropicalis is now being examined, and as well predictions of the 3D structure of the Xenopus IL7R α protein.
Effects of Ibuprofen and Fusion Protein Inhibitor (FPI) on neutrophil extracellular traps (NETs) in the lung tissue of calves experimentally infected with Bovine Respiratory Syncytial Virus (BRSV)
Authors: Mutua Victoria , Gershwin Laurel J
Published: January 2023

Neutrophil extracellular traps is a mode of neutrophil death targeting extracellular pathogens. They are composed of a complex of processed chromatin bound to granular and cytoplasmic proteins expelled from the cell onto pathogens. Although NETs play a role in trapping and killing extracellular pathogens they may be injurious and are considered to play a role in a wide array of inflammatory diseases. The exact contribution of NETs to clearance of pathogens versus inflammatory injury is poorly understood.

Bovine respiratory syncytial virus (BRSV), like RSV, causes severe respiratory disease.

In this study, we quantified NETs in lung tissue of calves experimentally infected with BRSV after treating with the anti-inflammatory drug Ibuprofen and/or an antiviral drug (FPI). Twenty four calves were infected with BRSV, placed into 6 treatment groups and treated with ibuprofen, FPI or both. Calves were euthanized on day 10 post infection and the lungs evaluated for pathological changes that were correlated with the IHC data. Cryosections of lung tissue were stained with primary antibodies [Rabbit anti citrinated histones(citH3), Rabbit anti neutrophil elastase (NE) and counter stained with secondary antibodies conjugated to Alexa 594 or 488. Slides were examined using an EVOS fluorescence microscope with at least 10 fields from each lung section at ×400 magnification evaluated. NETs were analyzed and quantitated using Materials Image Processing and Automated Reconstruction (MIPAR™) with the total NETs score calculated as the average of NETs in the 10 fields.

Results show that a combination of Ibuprofen and FPI treatment from day 3 following experimental infection had a significant reduction in clinical score and average NETs in lung tissue.
Lytic cell death mechanisms in human respiratory syncytial virus-infected macrophages
Authors: Bedient Lori , Pokharel Swechha Mainali , Casimiro Kim Roxana Chiok , Bose Santanu
Published: January 2023

Human respiratory syncytial virus (hRSV) is the most common cause of viral pneumonia in infants and children worldwide and creates significant airway disease in immunocompromised people and the elderly. Inflammation induced by hRSV infection is responsible for its hallmark manifestations of bronchiolitis and pneumonia. The cellular debris created secondary to lytic cell death of infected cells is a potent initiator of this inflammation. Macrophages are known to play a pivotal role in the early innate immune and inflammatory response to viral pathogens. While previous studies have investigated the mechanisms responsible for lytic cell death in Influenza A-infected macrophages and hRSV-infected neutrophils, the lytic cell death mechanisms associated with hRSV infection in macrophages remain unknown. In order to address this knowledge gap, we treated an hRSV-infected human THP-1 macrophage cell line with various inhibitors that block two lytic cell death pathways: pyroptosis and necroptosis. In addition, we used pyroptosis-deficient human macrophages to further clarify the lytic cell death mechanisms occurring during infection. Our studies revealed that hRSV induces lytic cell death in macrophages via both pyroptosis and necroptosis, specifically through caspase-1 and inflammasome-dependent pyroptotic mechanisms and through RIPK1-RIPK3-MLKL necroptotic mechanisms of cell death.
Expression and characterization of a monoclonal IgA isotype antibody against group 1 and group 2 influenza of the HV1-18 QxxV class
Authors: Ende Zachary S , Mishina Margarita , Kauffman Robert , Guo Zhu , Li Zhunan , Cao Weiping , Ray Sean , Kumar Amrita , Bohannon Caitlin D , Ranjan Priya , Sharma Suresh D , Gangappa Shivaprakash , Levine Min Z , Stevens James , Sambhara Suryaprakash
Published: January 2023

Examining cross-reactive influenza-specific human monoclonal antibodies can inform the rational design of universal flu vaccines. The vast majority of monoclonal antibodies studied to-date are of the IgG isotype or cloned into IgG vectors for expression. However, IgA isotype antibodies are also of interest, especially given their increased concentrations in the respiratory tract where the influenza virus replicates. To acquire anti-influenza monoclonal antibodies that are of both IgG and IgA isotypes, we used a fluorescently labeled hemagglutinin (HA) for fluorescence-activated cell sorting on memory B cells 14 days post-influenza vaccination. We then sequenced paired heavy and light chains with the 10× Genomics platform and chose relevant sequences to synthesize for expression and characterization. An IgA1 antibody of the HV1-18 QxxV class demonstrated binding to both group 1 and group 2 HA subtypes in enzyme-linked immunosorbent assays. Although Hemagglutinin inhibition assays were negative, neutralizing activity was positive in a microneutralization activity, at levels comparable to other published stalk-binding and neutralizing monoclonal antibodies, FI6v3 and CR9114. By testing the antibody against a panel of HA mutants, we found that the antibody bound to a region of the HA stalk previously reported for IgG1 antibodies of this class. Studies are on-going, but thus far demonstrate a broadly cross-reactive and neutralizing IgA antibody that recognizes the HA stalk of both group 1 and group 2 influenza viruses.
Pet shop mice are infected with a novel lymphocytic choriomeningitis virus strain that sustains an abundance of stem-like PD-1+ CD8 T cells
Authors: Beura Lalit K , Pierson Mark J , Wijeyesinghe Sathi P , Scott Milcah C , Semler Mathew R , Quarnstrom Clare , Hart Sara Hamilton , O’Connor David , Estes Jacob D , Vezys Vaiva , Masopust David
Published: January 2023

Lymphocytic choriomeningitis virus (LCMV) is a natural mouse pathogen. LCMV Armstrong, an acutely resolved strain, and LCMV Clone13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. Here, we describe LCMV Minnesota (LCMV-MN), which was transmitted to laboratory mice upon cohousing with pet shop mice and shares 80–95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in widely disseminated viral replication and viremia that was controlled within 15–30 days; which is of intermediate duration between LCMV Armstrong and Clone13. The magnitude of the LCMV-MN specific CD8+ T cell was maintained at much higher levels than that observed after LCMV Armstrong or Clone13 infections. LCMV-MN responding CD8+ T cells were further associated with significantly biased differentiation towards the recently described PD1+ CXCR5+ Tim-3lo stem-like CD8+ T cell population that was previously shown to be largely responsible for responsiveness to PD-1 inhibitory checkpoint blockade. In contrast to LCMV Clone13-induced responses, this subset persisted after resolution of LCMV-MN viremia, yet transcriptionally, phenotypically and functionally resembled PD1+ TCF1+ stem-like CD8+ T cells maintained by LCMV Clone13 infection. Together with existing models, LCMV-MN may contribute to a better understanding of the breadth of immune response in different chronic infections or tumor settings as well as the regulation of responsiveness to PD-1 blockade.
Virus-based vaccines with unique replication mechanisms differentially infect and activate dendritic cells leading to distinctive CD8+ T cell responses
Authors: Chiale Carolina , Robek Michael
Published: January 2023

The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vectors are not well understood. We hypothesized that highly immunogenic viral vectors with unique replication mechanisms but identical cell entry pathways differentially infect and activate DCs and promote antigen presentation that leads to efficient induction of distinctive antigen-specific T cell responses. To evaluate differences in replication mechanisms, we utilized a rhabdovirus vector (VSV) and an alphavirus-rhabdovirus hybrid vector (VLV), which replicates like an alphavirus but enters the cell via the VSV glycoprotein. We found that while virus replication promotes CD8+ T cell activation by VLV, replication is absolutely required for VSV-induced responses. DC subtypes were differentially infected in vitro with VSV and VLV, and displayed differences in activation following infection that were dependent on vector replication. Although bone marrow-derived DCs produced type I IFN when infected with the vectors, the mechanism of DC infection and activation was independent of type I IFN receptor signaling. Additionally, the ability of the alphavirus-based vector to generate CD8+ T cells in the absence of replication relied on cDC1 cells that promote antigen cross-presentation. These results highlight the differential activation of DCs following infection with unique viral vectors, and indicate potentially distinct roles of DC subtypes in activating the immune response following immunization.
A Comparison of Methods for Determination of Potency as Observed on a Group of Horses Immunized against Diphtheria
Authors: Leonard George F.
Published: January 2023

The potencies of antidiphtheritic sera obtained on trial bleedings during the course of immunization of a group of 20 horses were obtained by three different methods: The official test of the Hygienic Laboratory, based on prolongation of life of guinea pigs when injected subcutaneously with the trial serum along with an L + dose of standardized toxin. The so-called intracutaneous method, based upon the production of erythema at the site of intradermal injection into a guinea pig of a mixture of trial serum and standardized toxin. Flocculation in vitro when the trial serum is mixed with standardized toxin. The intracutaneous test yields results in closer agreement with those obtained by the official test than does the flocculation test. The last gives consistently lower values. The substantial accuracy of the intracutaneous test, as well as its economy of time and materials, makes it probably the method of choice for estimation of antidiphtheritic potency on trial bleedings.
Agglutinin Production in Suprarenalectomized Rats
Authors: Khorazo Devorah
Published: January 2023

Recent work of Jaffe and Marine (1) indicated that suprarenalectomized rats immunized with typhoid vaccine, within three weeks after operation, showed agglutinins against B. typhosus of a titer two to three times greater than that of normal rats similarly treated. On the other hand, Steinbach (2) found a lowering of resistance to tuberculosis in suprarenalectomized rats. This would seem to indicate that in spite of the fact Jaffe and Marine obtained an increase in antibody formation in suprarenalectomized rats, nevertheless the resistance of these animals to infection had been impaired by this operation. Therefore, because of the possible relationship which may exist between the suprarenal and antibody formation and of the discrepancy which seems to exist between antibody formation and resistance to disease, we have undertaken a series of experiments to repeat the work of Jaffe and Marine.

The present investigation was carried out in a manner similar to that described by these investigators.
Studies of the Properties of Bouillon Filtrates of the Meningococcus: Production of a Soluble Toxin
Authors: Ferry N. S. , Norton J. F. , Steele A. H.
Published: January 2023

No conclusive evidence has been found in the literature to prove that an extracellular or soluble toxin has been obtained from the meningococcus. The concensus of opinion is that the toxic reaction of this organism is due entirely to a substance or to substances intracellular or endotoxic in nature, and while the term “toxin” has been used rather loosely in the literature to identify the poisonous elements of this organism, it has referred specifically to products endoplasmic in character and not to those commonly classified as soluble toxins.

Zinsser (1) in his Textbook of Bacteriology states, “No soluble exotoxin has ever been conclusively isolated from the meningococcus” and he accounts for the so-called toxin on the ground that “A number of investigators have found that cultures that have been kept in broth long enough for a certain amount of extraction or autolysis to occur, yield toxic products which are in general identical in their action to that of whole meningococci injected in analogous quantities.”
Flocculation of Vaccinial Virus-Tissue Suspensions by Specific Antisera
Authors: Thompson Richard , Buchbinder Leon
Published: January 2023

The flocculation of vaccinial virus-skin suspensions by homologous antiserum noted by Gordon (5) and utilized by Burgess et al. (4) in the diagnosis of variola has been readily confirmed. The same antigens were also flocculated by immune sera against vaccinial brain and testicle tissues but not by sera from rabbits immunized against normal skin, normal brain, normal testicle, or streptococcal skin tissue. The sera from rabbits recovered from extensive vaccinial skin infections did not flocculate the virus-skin suspensions. Control antigens of normal skin and streptococcal skin suspensions were not flocculated by sera which caused marked flocculation of the virus-skin suspensions. Calf lymph and crusts from skin lesions of a small pox case were flocculated readily by antisera against the rabbit viruses. Brain and testicle virus suspensions, although they produced potent flocculating sera, were found to be unsuitable antigens for demonstrating the specific flocculation. There is a well marked correlation between the flocculating and neutralizing titers of the various antisera, although occasionally the neutralizing titer may be quite high in the absence of any flocculating power. The flocculating antibodies are specifically absorbed by the virus-skin suspensions and it is indicated, but by no means proved, that they are also absorbed by the non-flocculable virus brain and virus testicle antigens.
Studies on the Serological Reactions of the Flagella of B. Typhosus
Authors: Craigie James
Published: January 2023

A complement-fixation technique applicable to suspensions of the flagella of B. typhosus has shown that such suspensions deviate complement specifically in the presence of (a) somatic agglutinating sera, (b) pure flagellar agglutinating sera. The “antigen” which reacts with (a) is heat stable while that which reacts with (b) is not completely inactivated by exposure to 100°C. for one hour.

If the labilotropic agglutinin of Felix is identical with flagellar agglutinin then the double receptor hypothesis is of doubtful validity. The possibility that the complement-fixation technique adopted by this author is unsuited for the demonstration of fixation in which the labilotropic antibody is involved is discussed.

It is probable that flagella are much more sensitive to the action of agglutinating sera than are somata and, if so, the antibody content of flagellar and somatic sera cannot legitimately be compared on the basis of agglutinin titres. If the H titre of a serum gives an exaggerated impression of the amount of H antibody present the main arguments in favour of the double receptor hypothesis require reconsideration.

The author desires to record his indebteness to Professor W. J. Tulloch for the facilities which he has afforded for the work described in these papers, for his constant interest and for his advice and criticism.
A Method for the Agglutination of Hemolytic Streptococci
Authors: Mueller J. Howard , Klise Katharine S.
Published: January 2023

A simple method for agglutination of broth cultures of hemolytic streptococci is described which avoids in most instances the difficulty due to spontaneous agglutination in saline.
Parenteral Denaturization of Foreign Proteins
Authors: Sox Harold C. , Manwaring W. H.
Published: January 2023

Horse serum incubated in a mixture with 10 to 1000 volumes of normal canine serum, shows a fairly rapid and consistent destruction (or total denaturization) of proteins of full horse protein specificity, accompanied by an initial increase and subsequent gradual decrease in proteins intermediary in specificity between horse and dog.

These intermediary test tube products are apparently identical with the metaphorical “hybrid” specificities demonstrable in the canine circulation after intravenous injection with horse proteins.
Electric Charge of Bacterial Antigens
Authors: Olitzki Leo
Published: January 2023

A number of investigators have studied the nature of the electric charge of bacteria. Bechhold (1904) was the first to record the fact that bacterial cells carry a negative charge. Cernovodeanu and Henri (1906) studied a larger series of bacteria and reported that all species, except B. dysenteriae (Flexner), carried a negative charge; but the claim that the dysentery bacillus is electropositive has been contradicted by Szent-Gyorgi (1921). Since then a number of investigators have reported that bacteria migrate to the anode (Szent-Gyorgi (1921); Putter (1921); Winslow, Falk, and Caulfield (1923); Govaerts (1923)).

Winslow and his co-workers (1923, 1924) used the microscopic cell devised by Northrop (1922) to study the electrophoretic migration of a large number of microörganisms under a wide range of pH values. This method enabled the authors to determine the migration velocities of various microörganisms and particles in substrates having various pH values.
Bacterial Endotoxin
Authors: Hanks John H. , Rettger Leo F.
Published: January 2023

Since Pfeiffer (1894) first used the word “endotoxin” to describe the toxic substances which he derived from the cholera vibrio and the typhoid bacillus, numerous efforts have been made to demonstrate similar substances in various pathogenic organisms. A review of the voluminous literature which has accumulated on the subject of toxin production by members of the colon-typhoid group of bacteria reveals that the organisms employed in such investigations were grown under cultural conditions which are widely different from those of the animal body, and that, with few exceptions, the toxins thus obtained were studied in animals other than the natural host.

It would appear that the more nearly the conditions of the animal body are approximated in artificial culture the greater will be the possibility of the in vivo and in vitro metabolism of the parasite being similar or identical.

This consideration seems important in any study of the rôle of bacterial toxins in disease.
Purification of Concentrated Antitoxins
Authors: Gerlough Tillman D. , White Woodford
Published: January 2023

A study has been made of the application of the isoelectric method for further purification of concentrated antitoxins of varying age and previous treatment dialyzed to different specific conductances. The effectiveness of this method for removal of objectionable impurities was compared with that of fractional precipitation by salting out. The potency and amount of protein found in the isoelectric precipitates varied not only with age and previous treatment of the antitoxin, but also with the conductivity of the dialyzed solution. The specific conductance of the diluted antitoxin solutions which afforded optimum practical separations was found to be between 125 and 85 × 10-6. In the concentration of antitoxins, heating of the plasma renders subsequent isoelectric purification of the concentrates more effective for the removal of phosphorus bearing materials. After the removal of isoelectric protein from tetanus and diphtheria antitoxins and especially after electrodialysis the potencies of the fractions precipitated at lower concentrations of ammonium sulphate were increased. In the case of electrodialyzed tetanus the fractions precipitating between 34 and 43 per cent of saturation with ammonium sulphate, representing the bulk of the active protein, were of uniform potency. Data are submitted which show quantitatively the superiority of the isoelectric method over salt fractionation for removing euglobulin, fat and phospholipins from concentrated antitoxin.
Immunological Studies in Tuberculosis
Authors: Petroff S. A. , Steenken, W. , Winn W. A.
Published: January 2023

Discussion and Summary

The prevalence of avian tuberculosis has been pointed out in the preceding pages. What rôle this type of disease and avian tubercle bacilli play in the epidemiology of human infection and disease is not yet clear.

Human tuberculosis, as we see it today, is unquestionably due in most cases to human tubercle bacilli. The occasional isolation of types of bacilli from sputum or lesions of tuberculous patients which do not fit into the standard pattern of human, bovine and avian strains, suggest the possibility of a mutation. At present we have no definite proof that the avian organism may change into the human or bovine type. The only evidence we have is that it has apparently been isolated from human beings by Lowenstein, Urbach, Joannovich, Deutsch and others and that of L'Esperance finding it in Hodgkin's disease. Although the avian tubercle bacillus is found very rarely in human beings, we must take into consideration that this organism is a possible epidemiological factor when we map out our campaign against tuberculosis in man. The infection may enter the body either through eggs (raw or partially cooked) which contain the bacilli or through partially cooked chickens.

The eradication of avian tuberculosis must be advised not only for epidemiological reasons, but also as an actual practical economic factor.

In the past ten years attempts have been made to eliminate fowls reacting to tuberculin. This method has been moderately successful. We must hope also to direct our efforts to building up resistance to avian tuberculosis by some method of vaccination.

In this paper we have presented experimental studies using heat-killed and living avirulent organisms to produce sensitization. Chickens sensitized with various types of dissociated avian tubercle bacilli may be thus made tuberculin hypersensitive. Those sensitized with heat-killed “R” developed a greater sensitiveness; those sensitized with heat-killed “S” reacted to a lesser degree. The heat-killed undissociated culture and the living “R” inoculated into fowls were allergic only for a short period and showed a lower intensity (see tables 1, 2, 3 and 4). So far as this experiment can be taken as an indication, a greater degree of protection was demonstrated in chickens vaccinated with heat-killed “S” organisms. In this group 28 out of 48 fowls were free from tuberculosis. Unfortunately, 8 out of 42 controls were free from tuberculosis. We cannot explain at present these negative results in the controls. Possibly the first attempt to give them an enteric infection gave them a resistance against the intravenous infection. It will be noted histological examination revealed greater calcification and healing in the vaccinated fowls and especially those vaccinated with heat-killed “S” organisms.
Dissociation of the Specific Protein Precipitate of Antipneumococcus Horse Serum, and a Comparison with a Protein Isolated by Chemical Means from this Immune Serum
Authors: Felton Lloyd D.
Published: January 2023

Summary and Conclusions

Afterheating in 0.85 per cent sodium chloride with or without sodium carbonate (Gay and Chickering method), the relationship of protection to nitrogen was found to be approximately the same in precipitate and supernatant fluid of the pneumococcus carbohydrate-protein complex. It has been found possible to dissociate the specific precipitate, that is, separate the soluble specific substance from the protein by means of calcium or strontium phosphate. The protein thus separated is water-insoluble and salt soluble. In the material studied, it protects mice against one million lethal doses of virulent pneumococci, when the protein content is, in case of Type I, 0.0004 mgm. nitrogen per cubic centimeter, and with Type II 0.004 mgm. per cubic centimeter. The protein isolated by dissociation and that isolated by a zinc method are approximately alike in protective titer; both are water-insoluble, but readily soluble in neutral salts, and both alike react in similar fashion in all chemical analyses carried out. The nitrogen percentage by weight of the protein obtained by dissociation was with Type I, 14.9 per cent, and with Type II, 15.2 per cent. Three preparations by the zinc method gave respectively 15.7, 15.3 and 15.5 per cent nitrogen.
Agglutination Reactions in Rheumatoid Arthritis
Authors: Dawson Martin H. , Olmstead Miriam , Boots Ralph H.
Published: January 2023

In the preceding paper (1) it was shown that sera from the majority of patients with rheumatoid arthritis possess the property of agglutinating various strains of hemolytic streptococci to an extraordinarily high titer. No correlation was observed between the source of the strains and their agglutinability in the sera of rheumatoid arthritis patients. It was further shown that a variety of strains of other Gram-positive cocci were not agglutinated in a titer which was at all comparable with that obtained with strains of Streptococcus hemolyticus. An exception to this rule was observed in the case of strains of R pneumococci which were agglutinated in a titer almost as high as were strains of Streptococcus hemolyticus. In the present communication the nature of the agglutination phenomenon is analyzed and its possible significance is discussed.

Analysis of Patients Examined.

Early in the course of studies on the sera of rheumatoid arthritis patients it was observed that the agglutination phenomenon with hemolytic streptococci was subject to the widest variations.
The Mouse Protection Test on Antipneumococcic Serum Type I
Authors: Beard Stanley D. , Clapp Frances L.
Published: January 2023

In our paper of the above title, published in The Journal of Immunology, XXIII, No. 1, July, 1932, we inadvertently omitted reference to a paper by Falk, McGuire, Valentine and Whitney, published in The Journal of Immunology, XXI, No. 3, September, 1931, 199–219, in which the authors say in reference to the protection test on Antipneumococcic Serum Type I (page 203):

“Even with preparations which give irregular results on the individual experiments, it was found that if these experiments were repeated sufficiently frequently so that perhaps fifty to one hundred mice were tested at each dilution of antibody the total results would be progressively uniform, that is, with less antibody, a greater percentage of deaths.”

We regret that this observation escaped our memory, since our work in this respect confirms that of the above mentioned authors.
The Use of an Intradermal Test in the Diagnosis of Trichiniasis
Authors: McCoy O. R. , Miller J. J. , Friedlander R. D.
Published: January 2023

Of 36 persons ill with trichiniasis (i.e., two to six weeks after infection) 25 (70 per cent) gave positive immediate skin reactions following intradermal injection with 0.1 cc. of a 1:10,000 dilution (in terms of dry weight of powder) of a saline extract of Trichinella spiralis larvae. An additional 8 reacted to a 1:500 dilution of the antigen making a total of 33, or 92 per cent positive. Of 39 persons tested from three to twenty-two months after infection, 19 (49 per cent) reacted to the 1:10,000 dilution and an additional 12 were positive to a 1:500 dilution, a total of 31 or 80 per cent positive. Of 13 persons ill three and one-half to seven and one-half years prior to the test, 3 (23 per cent) were positive to the 1:10,000 dilution, and 5 more reacted to the 1:500 dilution, a total of 8 or 62 per cent positive. One hundred and four control persons from Rochester, New York, showed an incidence of 9 per cent positive with the 1:10,000 dilution and a total of 18 per cent positive with both the 1:10,000 and 1:500 dilutions. Forty-seven control persons from San Francisco, California, showed an incidence of only 4 per cent positive to the 1:10,000 antigen and 6.5 per cent positive with both the 1:10,000 and 1:500 dilutions. Ninety-two persons from southern Louisiana infected with Trichuris trichiura showed an incidence of 18 per cent positive with the 1:10,000 dilution and a total of 62 per cent with both the 1:10,000 and 1:500 dilutions. The practical use of the skin test in the diagnosis of trichiniasis is discussed.
Studies on Cultures and Broth Filtrates of Staphylococci. II
Authors: Burky Earl L.
Published: January 2023

The reactions of different types of rabbits to different types of filtrates are summarized in table 1 and confirm the findings of Burnet (2) and Parker (5) that immunity can be induced by intradermal injection of staphylococcus filtrates. This immunity manifests itself by a change in the skin reactions and a decrease in the lethal effect of toxic filtrates. Variation in reaction of rabbits is associated with the rabbits reaction to barium sulphide depilatory and probably the heredity of the animal.
Differentiation of Optically Isomeric and Related Cinchona Alkaloids by Quininesensitive Subjects
Authors: Dawson W. T. , Sanders J. P. , Tomlinson L. M.
Published: January 2023

The results of skin tests in three quinine-sensitive subjects with 42–48 cinchona alkaloids, including several pairs and one quartette of optical isomers, and with some chemically related substances show that the allergic reactions rest on somewhat different chemical bases in all three cases. In the optically isomeric quartette, quinine (ddll), epiquinine (ddld), epiquinidine (dddl) and quinidine (dddd) all three had allergic reactions to quinine that did not appear on administration of quinidine, and judging from skin tests were possibly insensitive to both epialkaloids also.

Results with five of the more common alkaloids in a fourth individual, with coryzal reaction to quinine, are given. Two other subjects, with urticarial reaction to quinine, had no such side effect from quinidine. These subjects with allergic reactions to quinine did not give positive skin scratch reactions to quinine.

A female subject with bleeding from the genital tract as a result of quinine administration was similarly affected by quinidine.
Merthiolate As a Preservative for Biological Products
Authors: Powell H. M. , Jamieson W. A. , Jones F. G.
Published: January 2023

Introduction. It is common knowledge that bacteriophage is somewhat more resistant to heat and the usual antiseptics than the homologous bacteria on which the bacteriophage is produced. Also, just as bacteria may vary among themselves in resistance to heat and chemicals, different bacteriophages may be found to vary in the same way. Furthermore, the same strains, either of bacteria or bacteriophage, may show considerable variation in these properties in different subcultures during laboratory propagation.

In a recent comprehensive study, using “raw” and “purified” bacteriophage, Kligler and Olitzki (1) found that the resistance of bacteriophage to antiseptics and heat depends to some extent on the associated proteins and other factors which may be present in different bacterial culture media. Adsorbed and eluted (“purified”) bacteriophage was markedly more labile than bacteriophage as it exists just after production in broth culture media. This paper is referred to simply as an example of conditions sometimes ignored.
H and O Agglutination Following Typhoid Vaccination and in an Unselected Group of Individuals
Authors: Dulaney Anna Dean , Wikle Walter T. , Stewart R. L. , Rayfield J. D. , Walker J. K. , Preacher A. B.
Published: January 2023

This paper presents the results of H and O agglutinations on 90 serums from individuals who had received triple typhoid (TAB) vaccine and on 100 unselected serums sent in for the Wassermann test.

The serums from vaccinated individuals were furnished by members of the class in Medical Bacteriology. Histories of previous vaccination or typhoid fever were obtained and these histories were properly considered in recording results.

It was impossible to obtain histories on the second group of serums but these were regarded as representative of any random group of individuals.

All of the serums were titrated for H and O typhoid agglutinin content using the formalinized antigen recommended by Dreyer (1) and an alcoholized antigen prepared according to Gardner's (2) method. A strain of typhoid which had been isolated from the blood stream of a patient six months previously was used for the preparation of the two antigens.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R.
Published: January 2023

Summary and Conclusions

The weight in itself of the host animals cannot be considered as having contributed more than a minor part in the differences in mortality between the strains. The stock of the latest average weight at injection showed the greatest proportionate number of resistant animals.

The determinative influence of the weight upon the variation in mortality within the various strains was variable, with a tendency in each for a lower mortality to be associated with the litters of greater weight.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R. , Hughes T. P.
Published: January 2023

The whole blood of rats from two inbred strains highly susceptible to infection with Salmonella enteriditis showed little or no bactericidal activity toward this organism. Those individuals whose blood showed varying degrees of bactericidal activity were, on experimental infection, approximately equally distributed in surviving and non-surviving groups.
The Effect of Flagellar and Somatic Sensitization of the Typhoid Bacillus on Phagocytosis by Macrophages and Polymorphonuclear Leucocytes—Intracellular Digestion
Authors: Mudd Stuart , Lucké Balduin , Strumia Max
Published: January 2023

Summary and Conclusions

Sera containing both flagellar and somatic antibodies against the typhoid bacillus and sera containing chiefly or only flagellar and chiefly or only somatic antibodies were prepared. Such sera were tested in parallel agglutination and phagocytosis experiments. Somatic sensitization has promoted phagocytosis of flagellate typhoid bacilli to an equal degree by both macrophages and polymorphonuclear leucocytes. The bacteriotropin effect has closely paralleled the agglutination in such experiments. Flagellar sensitization under the conditions of our experiments has promoted phagocytosis of flagellate bacilli by both macrophages and polymorphonuclear leucocytes. The phagocytosis-promoting effect in such experiments has been inferior both in completeness and in titer to the agglutination; this difference is readily explained, however, by the secondary physical factors involved in phagocytosis and agglutination. Intracellular digestion of typhoid bacilli occurs with great rapidity in both types of phagocytes. The phagocytic behavior of the two types of cells has been in essential agreement under the various conditions used in these experiments.
Certain Characteristics of the Water-Insoluble Protein of Normal as Compared with That of Antipneumococcus Horse Serum
Authors: Felton Lloyd D. , Kauffmann Gladys
Published: January 2023

The hydrogen ion concentration of minimum solubility of the water-insoluble protein of antipneumococcus horse serum soluble at various percentages of saturation with ammonium sulfate, namely 30, 36, and 50 per cent, was found to be as follows: for the 30 per cent, a zone between pH 5.8 and 5.9; for the 36 per cent, pH 6.1 to 6.2; and for the 50 per cent, pH 6.8 to 7.0. These same fractions of the protein obtained from normal horse serum all lay in the zone between pH 6.0 and 6.2. At the hydrogen ion concentration of minimum solubility, the protein of immune serum was from one-fifth to one-tenth as soluble as that obtained from normal serum. The protein obtained by dissociating the S. S.-antibody complex was found to have a hydrogen ion concentration of minimum solubility at pH 6.7 or above. The highest protective potency in relation to the amount of protein was found in the fractions precipitated by ammonium sulfate at 36 and 50 per cent saturation. The percentage of total serum protein (pooled serum) present in the different fractions was respectively, with 30 per cent, type I 4.6 per cent; normal 3.8 per cent; with 36 per cent, type I 7.3 per cent, normal 3.3 per cent; and with 50 per cent, type I 3.0 per cent, normal 0.9 per cent.
Effect of pH on Heat Inactivation of Tetanolysin
Authors: Schrek Robert
Published: January 2023

Introduction. Kyes and Sachs (1) in 1903 found that acidification of cobra lysin increased its thermostability. This finding was confirmed and extended by Morgenroth and Pane (2). Ando and Nishimura (3) observed recently that the heat stability of diphtheria toxin depended on the acidity, and that the acidified toxin withstood higher temperatures.

On the other hand, several investigators failed to observe any increase of thermostability of lysins after acidification. Famulener and Madsen (4) in a careful quantitative study found that both acidification and alkalization decreased the stability of tetanolysin to heat. Neill (5) did not observe any increase in the thermostability of lysin of B. welchii at pH's ranging between 3 and 9.

The present investigation is a continuation of these studies with reference to the effect of acidification and alkalization on the thermostability and oxidizability of tetanolysin.

Experimental. Methods. Tetanolysin; preparation and titration. Tetanolysin adjusted to various pH's was heated and was then neutralized and titrated.
Studies on Tissue Reactions in Immunity
Authors: Kahn Reuben L.
Published: January 2023

In the course of the studies on acquired sensitivity of rabbits to different organisms, previously reported (1), it had been observed that normal animals showed definite inflammatory responses to intradermal injections of bacterial suspensions of comparatively low concentration. The organisms employed were laboratory strains of B. typhosus, B. paratyphosus A, B. coli, Streptococcus hemolyticus and Staphylococcus albus that had been heated for one hour at 60°C. before use. If, for example, a skin sensitivity test, consisting of intradermal injections of 0.1 cc. quantities of suspensions containing varying numbers of organisms per cubic centimeter, was administered to a normal rabbit, inflammatory responses might have appeared in the course of twenty-four hours in the areas wherein the suspensions containing 1,000,000,000, 100,000,000 or perhaps 10,000,000 organisms per cubic centimeter, had been injected. These inflammatory responses were at first believed to be the result of endotoxins contained in the suspensions.
Studies on Cultures and Broth Filtrates of Staphylococci
Authors: Burky Earl L.
Published: January 2023

I. In previous reports (1), a toxin producing strain of staphylococcus has been described. This strain, “Ha,” produces in 10 day broth cultures a filterable substance that kills rabbits in twenty-four hours or less. The m.l.d. is about 0.1 cc. per kilogram of body weight. Whole cultures kill in a similar fashion. Burnet (2) has studied the lethal properties of similar strains and in particular, one strain, “Wood.” Filtrates of broth cultures of this strain kill rabbits in about five minutes after the intravenous injection of small amounts. A sublethal amount of filtrate, injected intracutaneously, produces an antiserum that neutralizes some, if not all, of the toxic properties of the filtrate. It is the belief of Burnet (2) that intracutaneous immunization produces the most potent antiserum. Further to confirm or disprove the findings of Burnet and to determine the precipitating and protective properties of filtrate Ha antiserums, the following studies were undertaken.
Immune Serum Production in Poliomyelitis Refractory Animals
Authors: Schultz E. W. , Gebhardt L. P.
Published: January 2023

Summary and Conclusions

Studies were carried out to determine the serological responsiveness of various poliomyelitis refractory animals injected with the virus of poliomyelitis. To this end 3 guinea pigs, 4 rabbits, 1 dog, 2 sheep, 1 goat and 1 horse were given repeated injections of suspensions of ground poliomyelitic cords over periods of time ranging from about six months to approximately two years. Virucidal tests were carried out on the sera of these animals at varying intervals of time during and after the period of more intensive virus injections. These virucidal tests were carried out by mixing 1 cc. of virus suspension with an equal volume of undiluted or previously diluted serum, following which the serum-virus mixtures were injected intracerebrally into monkeys. Titration of the virus suspension as well as the serum were carried out on several occasions. Our results confirm the observations of other investigators with reference to the degree in which poliomyelitis refractory animals respond as antiserum producers, the majority responding poorly or not at all to virus injections. Individual animals may, however, respond exceedingly well. A horse included in our series of animals proved exceptionally responsive. It produced a serum which contained sufficient immune substance per cubic centimeter to neutralize at least 25,000 minimum infecting doses of virus.
Experimental Observations on the Antigenic Potency of H. Pertussis Extracts
Authors: Miller J. J.
Published: January 2023

An attempt was made to compare the antigenic potency of extracts of H. pertussis with standard pertusis vaccine. The titer of complement fixing antibodies in rabbits after the injection of these agents was the index used. Observations on a small number of animals suggest the following possibilities.

Fresh extracts of recently isolated strains produce a more rapid rise in titer than does vaccine. The addition of formalin, chinosol and tricresol to these extracts delays the response. Filtration of the extract through a Berkefeld L2 filter removes the antigen. A more rapid response occurs with the small quantity of extract prepared from the given amount of concentrated bacterial suspension than with the large quantity of standard vaccine prepared from the same amount of concentrated bacterial suspension. Therefore the greater concentration of the antigen in the extract is not the factor responsible for the rapid rise obtained. The unfixed and extracellular state of the antigen is the factor responsible. The antigenic component of H. pertussis endotoxin is relatively thermostabile whereas the toxic component is inactivated by temperatures of 37° and higher.
Studies on Vascularization of the Cornea
Authors: Julianelle L. A. , Morris M. C. , Harrison R. W.
Published: January 2023

Summary and Conclusions

A study has been made in rabbits of the passive inducibility of the hypersensitive corneal reaction typified by clouding and vascularization. In these experiments, three methods were employed: (a) intravenous or local injection of specific precipitating serum followed later by injection of antigen (albumin), (b) combination of antiserum and antigen, (c) antigen and later antiserum—reversal of the method of passive anaphylaxis. With all three methods it was possible in certain instances to cause skin reactivity. The passive establishment of the corneal reactivity was not satisfactory. While the majority of the tests were negative, some were of the irritative variety described above rather than typical of hypersensitive corneal reactions. It is not clear, therefore, whether the evidence submitted indicates that corneal reactivity may be passively induced. The significance of the results is discussed.
Studies on Tissue Reactions in Immunity
Authors: Kahn Reuben L.
Published: January 2023

Introduction In the preceding article (1), data were presented dealing with some aspects of the union between specific antigen and the skin of protein-immunized rabbits. Horse serum was employed as the immunizing protein and horse serum antitoxin as the test antigen. It was believed that in testing the skin of the horse serum-immunized rabbits with antitoxin instead of horse serum, a more quantitative picture could be obtained of the skin response, since antitoxin can be measured quantitatively by its toxinneutralizing action. In practice, a lethal amount of diphtheria toxin and a neutralizing quantity of antitoxin were injected some distance apart into the skin of normal and of horse serumimmunized rabbits. The normal animals survived and the immunized animals succumbed. In the former animals, both the toxin and antitoxin diffused from the area of injection and the toxin was evidently neutralized in vivo.
Poliomyelitis
Authors: Kramer S. D. , Schaeffer M. , Park W. H.
Published: January 2023

Large batches of virus prepared by grinding and mixing many cords, preserved in 50 per cent sterile glycerine, retain a constant infectivity for at least twelve to eighteen months. A practical method for standardization of virus and immune serum is suggested. It is possible and practical to prepare large amounts of neutralized mixtures of virus and serum of known and constant value. Nine of twelve animals inoculated intramuscularly and subcutaneously with neutralized mixture of serum and virus developed sufficent immune substance in their blood serum so that 0.5 cc. of the serum neutralized ten infective doses of the virus. It is suggested that the reasons for the higher incidence of immune response obtained, may lie in the ratio of serum to virus in these mixtures.