bluuebunny/crossref_metadata_2025 huggingface dataset:
Amplitude and Frequency Modulation of Metabolic Signals in Leukocytes: Synergistic Role of IFN-γ in IL-6- and IL-2-Mediated Cell Activation
Authors: Adachi Yoshiyuki , Kindzelskii Andrei L. , Ohno Naohito , Yadomae Toshiro , Petty Howard R.
Published: December 2022

Many stimuli cause intracellular concentration oscillations of second messengers or metabolites, which, in turn, may encode information in their amplitudes and frequencies. We now test the hypothesis that synergistic cellular responses to dual cytokine exposure correlate with cross-talk between metabolic signaling pathways of leukocytes. Polarized RAW264.7 macrophages and human neutrophils and monocytes exhibited NAD(P)H autofluorescence oscillation periods of ≅20 s. IFN-γ tripled the NAD(P)H oscillatory amplitude for these cells. Although IL-6 had no effect, incubation of cells with IFN-γ and IL-6 increased both oscillatory amplitude and frequency. Parallel changes were noted after treatment with IFN-γ and IL-2. However, IL-1β and TNF-α did not display frequency doubling with or without IFN-γ exposure. To determine whether frequency doubling required complete IFN-γ signaling or simply metabolic amplitude modulation, an electric field was applied to cells at NAD(P)H troughs, which has been shown to enhance NAD(P)H amplitudes. Electric field application led to frequency doubling in the presence of IL-6 or IL-2 alone, suggesting that amplitude modulation is crucial to synergism. Because NADPH participates in electron trafficking to NO, we tested NO production during cytokine exposure. Although IL-6 and IL-2 alone had no effect, IFN-γ plus IL-6 and IFN-γ plus IL-2 enhanced NO release in comparison to IFN-γ treatment alone. When NO production was examined for single cells, it incrementally increased with the same phase and period as NAD(P)H. We suggest that amplitude and frequency modulation of cellular metabolic oscillations contribute to intracellular signaling synergy and entrain NO production.
A Recurrent Breakpoint in the Most Common Deletion of the Ig Heavy Chain Locus (del A1-GP-G2-G4-E )
Authors: Brusco Alfredo , Saviozzi Silvia , Cinque Fernanda , Bottaro Andrea , DeMarchi Mario
Published: December 2022

Human Ig heavy chain constant regions are encoded by a cluster of genes, the IGHC locus, on 14q32.3. Several forms of IGHC deletions and duplications spanning one to five genes have been described in different populations, with frequencies of 1.5–3.5% and 4.5–44%, respectively. Despite the common occurrence of these gene rearrangements, little is known about the breakpoint sites; evidence obtained from deletions in the IGHC locus and in other regions of the human genome suggests that they preferentially occur in highly homologous regions and might be favored by a variety of recombinogenic signals. We present here a detailed study of three homozygotes for the most common type of IGHC multiple gene deletion, spanning the A1-GP-G2-G4-E genes. Using a combination of Southern blotting, long-range PCR, and automated sequencing, the unequal crossover events of all of the six studied haplotypes have been mapped to a region of ∼2 kb with almost complete homology between EP1-A1 and E-A2, flanked by two minisatellites. These results are consistent with the hypothesis that segments of complete homology may be required for efficient homologous recombination in humans. The possible role of minisatellites as recombination signals is inferred, in agreement with current knowledge.
Surfactant Protein A Down-Regulates Proinflammatory Cytokine Production Evoked byCandida albicansin Human Alveolar Macrophages and Monocytes
Authors: Rosseau Simone , Hammerl Peter , Maus Ulrich , Günther Andreas , Seeger Werner , Grimminger Friedrich , Lohmeyer Jürgen
Published: December 2022

Surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammatory events. We analyzed the impact of SP-A on the Candida albicans-induced cytokine response in human alveolar macrophages (AM) and its precursor cells, the monocytes, which rapidly expand the alveolar mononuclear phagocyte pool under inflammatory conditions. Both recombinant human SP-A and natural canine SP-A were employed. SP-A dose-dependently down-regulated the proinflammatory cytokine response of AM and monocytes to both viable and nonviable Candida, including TNF-α, IL-1β, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1. In contrast, SP-A did not affect the baseline liberation of these cytokines. The release of the antiinflammatory cytokines IL-1 receptor antagonist and IL-6 was not inhibited by SP-A under baseline conditions and in response to fungal challenge. The inhibitory effect of SP-A on proinflammatory cytokine release was retained upon reassembly of the apoprotein with natural surfactant lipids and in the presence of serum constituents, for mimicry of plasma leakage into the alveolar space. It was not reproduced by the homologous proteins complement component C1q and type IV collagen. It was independent of Candida-SP-A binding and phagocyte C1q receptor occupancy, but apparently demanded SP-A internalization by the mononuclear phagocytes, effecting down-regulation of proinflammatory cytokine synthesis at the transcriptional level. We conclude that SP-A limits excessive proinflammatory cytokine release in AM and monocytes confronted with fungal challenge in the alveolar compartment. These data lend further credit to an important physiological role of SP-A in regulating alveolar host defense and inflammation.
Paired Stat6 C-Terminal Transcription Activation Domains Required Both for Inhibition of an IFN-Responsive Promoter andTrans-Activation
Authors: Goenka Shreevrat , Youn Jeehee , Dzurek Linda M. , Schindler Ulrike , Yu-Lee Li-yuan , Boothby Mark
Published: December 2022

The cytokines IL-4 and IFN-γ exert biologically antagonistic effects that in part reflect opposing influences on gene transcription. While the molecular mechanisms for IL-4-mediated transcription activation have been extensively studied, little is known about molecular mechanisms required for IL-4 inhibition of IFN-γ signaling. We have investigated IL-4 inhibition of the IFN-γ-inducible promoter for IFN regulatory factor-1 (IRF-1). In a cell line with low endogenous Stat6, increasing levels of activated Stat6 at constant doses of IFN-γ and IL-4 leads to inhibition of the IRF-1 promoter. The Stat1-dependent IFN-γ activation sequence element of the IRF-1 promoter is a target for Stat6-mediated inhibition despite apparently normal Stat1 DNA binding. However, our data are inconsistent with competition between Stat1 and Stat6 for access to the IRF-1 IFN-γ activation sequence or for an essential coactivator as a mechanism for this Stat6-mediated inhibition. Instead, the data demonstrate that a threshold of Stat6 transcription activation domains is required for IL-4-dependent inhibition. The findings provide evidence of a novel mechanism in which the Stat6 transcription activation domains play a critical role in the IL-4-mediated inhibition of an IFN-γ-inducible promoter.
Presence of CpG DNA and the Local Cytokine Milieu Determine the Efficacy of Suppressive DNA Vaccination in Experimental Autoimmune Encephalomyelitis
Authors: Lobell Anna , Weissert Robert , Eltayeb Sana , Svanholm Cecilia , Olsson Tomas , Wigzell Hans
Published: December 2022

We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68–85, against Lewis rat experimental autoimmune encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5′-AACGTT-3′ motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68–85 and containing three ISS of 5′-AACGTT-3′ sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-α with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-α-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We conclude that the presence of ISS and induction of a local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.
A “Stealth Effect”: Adenocarcinoma Cells Engineered to Express TRAIL Elude Tumor-Specific and Allogeneic T Cell Reactions
Authors: Giovarelli Mirella , Musiani Piero , Garotta Gianni , Ebner Reinhard , Di Carlo Emma , Kim Yunsoo , Cappello Paola , Rigamonti Laura , Bernabei Paola , Novelli Francesco , Modesti Andrea , Coletti Anna , Ferrie Ann Kim , Lollini Pier-Luigi , Ruben Steve , Salcedo Theodora , Forni Guido
Published: December 2022

BALB/c mammary adenocarcinoma cells engineered to express TNF-related apoptosis-inducing ligand (TRAIL)/APO-2 ligand (APO-2L) on their membrane (TSA-TRAIL) grow with kinetics similar to that of parental cells (TSA-pc) in vitro and in nu/nu mice. In contrast, TSA-TRAIL cells grow faster than TSA-pc in normal BALB/c mice. In DBA/2 mice, which differ from BALB/c mice at minor histocompatibility Ags, they also grow faster and display a higher percentage of tumor takes than TSA-pc. In fully histoincompatible C57BL/6 (B6) mice, TSA-TRAIL cells form evident tumors that are slowly rejected by most mice, but outgrow in a few. In contrast, TSA-pc cells are rejected at once by B6 mice. Since TRAIL/APO-2L induces apoptosis by interacting with a variety of specific receptors, this rapid growth in both syngeneic and allogeneic mice may be the result of an immunosuppressive mechanism. The following evidence supports this hypothesis: 1) TSA-TRAIL cells overcome the strong immunity against TSA-pc cells elicited in BALB/c mice by preimmunization with TSA cells engineered to release IL-4; 2) their rejection by B6 mice does not prime a CTL-mediated memory; 3) thymidine uptake by T lymphocytes unstimulated or stimulated by allogeneic cells is inhibited when TSA-TRAIL cells are added as third party cells; 4) CTL kill TSA-pc but not TSA-TRAIL cells in 48-h assays; and 5) activated lymphocytes interacting with TSA-TRAIL cells in vivo and in vitro undergo apoptosis.
Cloning and Characterization of a Novel Activating Ly49 Closely Related to Ly49A
Authors: Makrigiannis Andrew P. , Gosselin Pierre , Mason Llewellyn H. , Taylor Lynn S. , McVicar Daniel W. , Ortaldo John R. , Anderson Stephen K.
Published: December 2022

The majority of the known Ly49 family members have been isolated from either C57BL/6 (B6) or BALB/c mice. Interestingly, the anti-Ly49 Ab reactivities observed in 129/J mice are different from those of B6 mice. Furthermore, immunoprecipitation of 129/J NK cell lysates with YE1/32 and YE1/48, Abs specific for the inhibitory Ly49A in B6, resulted in detection of the activation-associated DAP12 molecule. These results indicated a need for a more detailed study of this strain. Therefore, a cloning strategy was devised to isolate Ly49 cDNAs from 129/J mice. An immunoreceptor tyrosine-based inhibitory motif-containing, Ly49D-related clone was discovered that we have named Ly49O, and one immunoreceptor tyrosine-based inhibitory motif-lacking, Ly49A-related clone was discovered that we have named Ly49P. No anti-Ly49 mAb reacted with Ly49O, whereas the molecule encoded by the Ly49P cDNA was found to react with YE1/32 and YE1/48. Ly49P was found to associate with mouse DAP12, and Ab-mediated cross-linking of Ly49P resulted in mouse DAP12 phosphorylation and Ca2+ mobilization, indicating that Ly49P is a competent activation receptor. Ly49P, therefore, represents a novel member of the Ly49 activating receptor subfamily.
Nitric Oxide and the Th2 Response Combine to Prevent Severe Hepatic Damage DuringSchistosoma mansoniInfection
Authors: Brunet L. Rosa , Beall M. , Dunne D. W. , Pearce E. J.
Published: December 2022

During infection with Schistosoma mansoni, NO production increases following the deposition of parasite eggs in the liver. In wild-type C57BL/6 mice, NO levels peak during the sixth week of infection and are subsequently down-regulated. Inducible NO synthase (iNOS) mRNA was found in diseased liver tissue along with TNF-α and IFN-γ, which are known promoters of iNOS expression. Mice treated with aminoguanidine, a selective inhibitor of iNOS, exhibited cachexia and exacerbated liver pathology, suggesting that NO limits hepatocyte damage when the liver is first exposed to eggs. Hepatic iNOS is up-regulated in SCID mice, indicating that NO production is part of an innate response. Studies with infected highly susceptible IL-4−/− mice revealed that prolonged NO production is in itself deleterious and that a major function of the Th2 response, which is severely compromised in the absence of IL-4, is to regulate NO production. In these animals, plasma NO levels are high compared with those in infected wild-type mice and remain elevated until death. Nevertheless, the underlying importance of NO is illustrated by the finding that aminoguanidine treatment leads to more severe liver disease and reduced time to death in infected IL-4−/− mice.
Neutralization of Endogenous Granulocyte-Macrophage Colony-Stimulating Factor Subverts the Protective Immune Response toHistoplasma capsulatum
Authors: Deepe George S. , Gibbons Reta , Woodward Erin
Published: December 2022

We examined the influence of endogenous GM-CSF on the course of primary and secondary pulmonary histoplasmosis. A high proportion (≥75%) of C57BL/6 mice given mAb to GM-CSF did not survive primary infection, whereas 88–94% of infected controls survived. Analysis of leukocytes revealed significantly fewer CD4+ and CD8+ cells in lungs, but not airways, of anti-GM-CSF-treated mice as compared with infected controls. However, the histopathology was similar between the two groups. Lungs of mice given mAb to GM-CSF manifested depressed levels of TNF-α, IFN-γ, and reactive nitrogen intermediates and elevated levels of IL-4 and IL-10. Administration of mAb to IL-4, to IL-10, or both restored protective immunity in GM-CSF-neutralized mice. In secondary infection, administration of mAb to GM-CSF exacerbated infection but did not alter survival over 30 days. The character of the inflammatory response was similar, and no differences were detected in Th1 or Th2 cytokine production between the two groups. Thus, endogenous GM-CSF is essential for survival in primary but not secondary infection, and blockade perturbs protective immunity. These findings reveal a new mechanism whereby GM-CSF contributes to host protection and demonstrate differences in control of primary and secondary histoplasmosis.
C1q and C4b Bind Simultaneously to CR1 and Additively Support Erythrocyte Adhesion
Authors: Tas Sander W. , Klickstein Lloyd B. , Barbashov Sergei F. , Nicholson-Weller Anne
Published: December 2022

Previously, we showed that soluble C1q bound specifically to CR1 on transfected cells. If the CR1-C1q interaction were to participate in immune complex clearance, then this interaction should support E adhesion. Using a tip plate adhesion assay, we found that immobilized C1q mediated adhesion of human E. E binding to C1q was specifically inhibited by polyclonal anti-CR1 Fab fragments. Intact C1 was not efficient as an adherence ligand until it was treated with EDTA or the C1 inhibitor to remove the C1r2C1s2 complex from C1, leaving C1q. Titration of C1q alone, C4b alone, and C1q + C4b indicated that the two complement ligands were additive in their ability to support CR1-mediated adhesion of E. Analysis of binding to immobilized CR1 using a BIAcore instrument documented that C1q, C4b, and C3b binding were independent events. Additionally, C1q-dependent binding of immune complexes and heat-aggregated IgG to E was documented. These experiments confirm that the immune adherence receptor in humans, CR1, is the single receptor for all of the opsonic ligands of complement, provide evidence for a single C1q binding site on LHR-D of CR1, and suggest that C1q may participate in immune clearance.
The Deterioration of Diphtheria Toxin in Dilution
Authors: Dow Jessie E.
Published: December 2022

Dilutions of freshly prepared diphtheria toxin of 1:100 or less in phenolized 0.85-per-cent NaCl solution, while stored at from 3° to 8°C. for approximately two years, followed a curve of deterioration similar to that of the undiluted toxins from which they were made. After reaching a state of relative stability such dilutions withstood, without appreciable loss in potency, five days' exposure to conditions involving moderate temperatures and transportation. The 1:100 dilutions did not maintain their potency when subjected for five days to conditions involving extreme heat and transportation, although the routine undiluted toxin for the Schick test which accompanied them gave no evidence of deterioration. The dilutions were also affected by frequent alternations between room temperature and extreme cold.
Studies in Isohemagglutination
Authors: Polayes S. H. , Lederer M. , Wiener A.S.
Published: December 2022

Summary and Conclusions

The agglutinogen and agglutinin contents of maternal and cord bloods were studied in 500 cases.

The mothers' bloods were found to occur in the following groups in order of frequency: A, β, 40.0 per cent; O, αβ, 37.4 per cent; B, α, 16.8 per cent; and AB, o, 5.8 per cent. The cord bloods were classified in the following subdivisions2 in order of frequency: A, o, 24.6 per cent; A, β, 15.0 per cent; O, αβ, 14.4 per cent; O, o, 12.4 per cent; B, o, 10.0 per cent; B, α, 9.4 per cent; O, β, 6.0 per cent; AB, o, 4.6 per cent; O, α, 3.6 per cent. When classified according to agglutinogen content, however, the cord blood groups and maternal blood groups occurred in nearly the same frequency. The full quotient of agglutinogen and agglutinins were found in 43.4 per cent of the cord bloods.

In tabulating the number of offspring from the A, β; B, α; AB, o; and O, αβ mothers, and arranging the cord bloods in their nine different subdivisions, two very interesting phenomena were observed: Firstly, in no case did the cord blood contain agglutinins specific to the mother's cells. It was observed, however, that out of the 500 cases examined, about 25 per cent of the cord bloods were incompatible with the blood of their respective mothers, the incompatibility being due to the agglutination of the cells of the cord blood by the serum of the mother, and never vice versa. These findings suggest the presence of a protective mechanism against danger to the mother in case of passage of the child's serum into the maternal circulation. Secondly, out of 187 cases of O, αβ mothers, not one group AB, o offspring was found. Similarly, not a single group O, αβ offspring was found out of 29 group AB, o mothers. This strengthens Bernstein's multiple-allelomorph theory.
A Simple Method of Obtaining Soluble Specific Substances from Various Bacteria (Streptococcus Viridans, B. Dysenteriae and B. Mallei)
Authors: Ando K.
Published: December 2022

Chemical and immunological studies to determine the nature of the substances responsible for the specific reactions of a number of microorganisms have been reported recently by several investigators. If the conclusions of Avery and Heidelberger in regard to the pneumococcus should be found to be applicable to other species of bacteria, some problems such as diagnosis of glanders and also the question in regard to the variety of B. dysenteriae may be simplified or solved. As it seemed that studies on such problems have not been reported on account of the difficulties encountered in the method of isolating the specific substance, simpler methods of obtaining this substance in a relatively pure form were sought.

After confirming the results of Lancefield on Streptococcus viridans, we have succeeded in isolating a soluble specific substance from the glucose broth culture filtrate of Streptococcus viridans in a simple manner according to a modification of Avery and Heidelberger's method.
The Production of Antibodies for Cypridina Luciferase and Luciferin in the Body of a Rabbit
Authors: Harvey E. Newton , Deitrick John E.
Published: December 2022

An antiluciferase can be produced in the blood of rabbits by repeated injection of luciferase solution prepared from the luminous ostracod crustacean, Cypridina hilgendorfii. The antiluciferase is not destroyed by a temperature of 56 or 61° for thirty minutes but is destroyed at 71° for thirty minutes and 95° for five minutes. No indication that complement is necessary for the action of antiluciferase was obtained.

No indication that antiluciferin can be produced in the blood of rabbits was obtained.

The results suggest that luciferase is a protein or associated with protein, whereas luciferin is not an antigenic protein.
Allergic Testis Reactions in Guinea Pigs with Coccidioidal Granuloma
Authors: Hirsch Edwin F. , D'Andrea Dorothy
Published: December 2022

The testes of guinea pigs with coccidioidal granuloma respond to injections of broth culture filtrates of coccidioides immitis, as do other allergic tissues in the presence of antigen, by the appearance of an acute inflammatory exudate far in excess of that in the tissues of uninfected hosts similarly injected.

These results are further evidence that the tissue reactions of hosts with coccidioidal granuloma injected with culture filtrates of coccidioides immitis are allergic.
Study of a Case of Hodgkin's Disease in a Child
Authors: L'Esperance Elise S.
Published: December 2022

The results of a previous study of 2 cases of Hodgkin's disease seemed to constitute prima facie evidence of the probable etiological significance of the avian tubercle bacillus in that disease. This evidence could not be considered conclusive on account of the small number of experiments and the lack of pure cultures of that microörganism from the inoculated birds.

The present study confirms the previous findings and includes the successful isolation of an acid-fast bacillus possessing many of the cultural characters of the avian tubercle bacillus from chickens and guinea pigs, which were infected with tissue from Hodgkin's granuloma.

The material for this study was obtained from the New York Hospital through the courtesy of Dr. James Denton, and consisted in the organs from a fatal case of Hodgkin's disease in a female child of eight years.

This previously healthy child of normal parents had a routine tonsillectomy and one month after this operation developed a low fever ranging to 102°F.
The Relationship of Two Hemotoxic Antigens in B. Welchii Growth Products
Authors: Schnayerson A. F. , Samuels S. L.
Published: December 2022

In the sterile filtrates of B. welchii broth cultures two hemotoxins have been demonstrated. One of these designated as A is active in vitro and probably to some extent in vivo; the other, B, causes no hemolysis in vitro but marked blood destruction in vivo. These two principles were not completely separated.

The hemotoxin A (hemolysin) was produced in such strength that 0.0075 cc. completely lysed 1 cc. of 5 per cent washed red blood sheep cells in eighteen hours.

Hemotoxin B was generally found to be much more toxic for pigeons than A.

Immune sera were produced with these two hemotoxins. It was found that anti-hemotoxin A serum in high dilution would neutralize its homologous antigen whereas anti-hemotoxin B had no effect on it.

On intravenous inoculation into rabbits it has been found that hemotoxin B alone caused approximately as marked an anemia as a mixture of A and B. Although A apparently gave rise to a more rapid initial hemolysis in vitro than B, the continuing anemia and morphological blood changes were evidently due to the action of hemotoxin B.
The Rate of Disappearance of Injected Horse Serum from the Blood of the Rabbit
Authors: Dean H. R. , Goldsworthy N. E. , Broeck C. Ten
Published: December 2022

A series of rabbits have received intravenous injections of horse serum, usually 10 cc. Samples of blood have been taken from these rabbits at intervals from a few minutes to twelve days after the injection. The volume of horse serum present in the rabbit serum obtained from these samples has been determined by the optimal proportions method. The blood volume of each rabbit has been calculated by a formula put forward by G. Dreyer and W. Ray (1912) and the serum volume has been taken as 60 per cent of the blood volume. The results obtained by the titration of each sample together with the calculated serum volume of the rabbit provide data for the estimation of the volume of horse serum present in the blood of the rabbit at various intervals after the injection. In a considerable proportion of the experiments the results obtained during the first hour after the injection have yielded ridiculously high figures, results indeed which appeared to show that the rabbit's blood contained more horse serum than had in fact been injected. In other experiments the results obtained from the titration of the earlier samples were more reasonable. A satisfactory explanation of the more surprising results has not been found. In all experiments the rate of disappearance of horse serum from the blood of the rabbit was rapid during the first six hours after which on an average about 50 per cent of the injected horse serum had disappeared. After the sixth hour the rate of disappearance was much more gradual. Quantitative determinations of the volume of the horse serum which remained in the rabbit's blood, could be made until about the eighth day when rather less than ten per cent of the injected volume of horse serum remained.
The Nature of the So-Called Conglutination Reaction (Bordet-Streng)
Authors: Eagle Harry
Published: December 2022

The adsorption (fixation) of complement midpiece by antigen-antibody suspensions (sensitized red cells or bacteria; specific precipitate) causes a change in their surface properties, evidenced by an increased tendency to cohesion and flocculation.

So-called conglutination is simply a specific instance of this general property of complement-midpiece, involving sensitized cells and the slight quantities of midpiece present in heated sera.

Since the terms conglutinin and conglutination do not define a distinctive substance or reaction, it is suggested that they be dropped from immunologic nomenclature.
Studies in Isohemagglutination
Authors: Wiener Alexander S. , Lederer Max , Polayes S. H.
Published: December 2022

Summary and Conclusions

The bloods of 1334 mothers and their 1462 children were typed. Although 485 group O mothers with 516 children and 94 group AB mothers with 142 children were examined, not once did the combinations AB mother—O child or O mother—AB child appear. The authors' data together with Schiff's and Thomsen's, therefore completely support the Bernstein theory.

A survey of the literature shows that many apparent exceptions were found. On careful analysis of these cases, not a single completely proven exception to Bernstein's theory could be found.

It may therefore be concluded that although the existence of bona fide exceptions to the Bernstein theory cannot be entirely disproved, it is certainly true that of all the theories of heredity of blood groups, Bernstein's theory agrees best with the facts. Any true exceptions to this theory may be due to other factors complicating the mechanism of heredity.
The Antigenic Substances of the Tubercle Bacillus
Authors: Dienes L. , Schoenheit E. W.
Published: December 2022

In the filtrates of cultures grown on the synthetic medium of Long, beside the carbohydrate precipitable substance, we can demonstrate the presence of two antigenic substances. They are separated from each other by acid precipitation. Both by the serological reactions and the antibody production these antigens are well differentiated from each other and from the other antigens of the tubercle bacillus. The difference between these two fractions can be observed also concerning the tuberculin reaction in guinea pigs treated with one or the other of these preparations.

The acid-precipitable antigen readily forms antibodies in tuberculous animals which are specific toward this antigen. The acid non-precipitable fractions did not form antibodies reacting with the same preparations or with the acid precipitate and concentrated culture medium, but the sera of the majority of the guinea pigs treated with these preparations gave strong reactions with the bacillary emulsion.

From the observations that neither of the two antigens separated by acid precipitation or their mixture gave a positive reaction with several sera produced with the concentrated culture medium and that the latter did not react with the sera produced with the acid precipitate we draw the conclusion that in the culture medium the antigens which are separated by acid precipitation are united in a higher complex which has a specificity markedly different from that of the isolated antigens, and in the reactions of which the effect of the isolated antigens does not appear. The differences which we found concerning the serological reactions between the culture filtrate of different tubercle bacillus strains are probably caused not by the absence or presence of a certain antigen, but by the differences in the way in which the acid-precipitable part is united to the higher complex.

Probably the above mentioned complex antigen is responsible for the production of antibodies by the concentrated culture medium and the acid filtrate, although this complex often gives no, or gives only a slight, reaction with these sera.
The Titration of Scarlatinal Antitoxin in White Pigs
Authors: Ando K. , Kurauchi K.
Published: December 2022

The relative merits and limitations of various methods of titrating scarlet fever antitoxin reported by many authors have been described and discussed in brief.

A method of titration of scarlatinal antitoxin with white pigs has been described. This method is not only convenient, but also reasonable since firstly the substance which is responsible for the skin reaction of white pigs was proved to be the essential scarlatinal toxin, and secondly this animal does not react to the nucleoprotein contained in the ordinary Dick toxin which may interfere with the results of the skin test method on human beings.
Certain Characteristics of the Infectious Processes in Connection with the Influence Exerted on the Immunity Response
Authors: Dienes L. , Schoenheit E. W.
Published: December 2022

The observations described in this paper inform us concerning important properties of the lesions, with the help of which the production of the tuberculin type of sensitiveness is successful. Twenty-four hours after the injection of a large dose of the R1 strain into the testicle, the injection of eggwhite in the same place produces tuberculin type of sensitiveness. When intraparitoneal injections are used, forty-eight-hour intervals were necessary between the two injections. In the production of the sensitiveness the local reaction at the site of the tubercle bacillus injection played the preponderant rôle because only the injection of eggwhite in this place was effective. The intravenous injection of small doses is without effect. At the stage when we injected the eggwhite an acute inflammatory reaction is present, with large accumulation of leucocytes around the injected bacteria. The typical tissue reaction of tuberculosis is not yet developed. The latter is not a prerequisite of the development of the tuberculin type of sensitiveness.

It was possible to produce a tuberculin type of sensitiveness with the injection of eggwhite into the testicle of guinea pigs infected with smallpox vaccine.

With extensive acute inflammatory processes produced with infusorial earth, tapioca, turpentine, the immunity response of the animals was not influenced. The local reactions produced with the antigenic lipoid substances of the tubercle bacilli also remained without effect.

With the soluble substances of the tubercle bacillus we did not succeed in increasing the antigen response. Different considerations make it improbable that the substances of the bacterium are directly responsible for the influence exerted by the lesions on the immunity response.

We give also a review of unsuccessful experiments in which we tried to transfer passively the increased response toward the antigens with the products of tuberculous lesions.
Effect of Repeated and Continuous Peptone Injections and Ingestion in Dogs
Authors: Petersen WM. F. , Müller E. F. , Saelhoff C.
Published: December 2022

In previous communications we have published experiments dealing with the effect of continuous injections of antigen in sensitized dogs (1) and of suspension of B. coli in normal dogs (2) and have discussed the correlation of lymph and blood chemistry with the clinical effects observed (3).

In this paper we should like to present graphs illustrative of the changes that are to be observed when Witte peptone is injected either continuously or at repeated intervals in animals with thoracic duct incannulation and also the effect on the leucocyte curve following repeated ingestion of a meat peptone prepared in the laboratory.

Experimental. Normal dogs were used and thoracic duct incannulation made under local anesthesia. After a period of observation, the injection of peptone was made intermittently—with small doses at repeated intervals—or continuous injections were made with the Woodyat Pump. The technic has been completely described in previous publications (4).

Experiment 7 (chart 1).
The Reaction of the Human Skin to Normal and Immune Guinea Pig Serum
Authors: Ramsdell Susan Griffith
Published: December 2022

The human skin reacts rather regularly, with the immediate type of reaction, to normal guinea pig serum in a dilution of 1:10, and to a lesser degree to one of 1:50. Usually, after this reaction, the skin becomes normal in appearance in two to twenty-four hours. When an anti-human serum in a dilution of 1:10 is injected, the immediate reaction is not always greater than that due to the normal serum. But a difference is made more evident by using higher dilutions of the sera, indicating a specific antigen-antibody response. A further difference in the reactions is seen in the persistence of that to the immune serum, with induration and inflammation for twenty-four hours. The degree of the reaction, with both sera, is only slightly reduced by heating the sera for ten minutes at 50°C.
On the Dialyzability of Proteins
Authors: Coca Arthur F.
Published: December 2022

The dialyzability of the excitants of atopic hypersensitiveness in egg-white reported by W. Jadassohn is confirmed. With the aid of specific antisera and chemical methods the dialyzable excitants are shown to be native proteins. The proteins in the dialysate are antigens.
The Transfer of the Skin-Reacting Antibody in Human Serum to Guinea Pig Skin
Authors: Ramsdell Susan Griffith
Published: December 2022

A specific reaction in the guinea pig skin may be obtained, with fair regularity, where the test-antigen can be used in a considerable concentration, on transfer of the serum of asthmatic subjects to the animal skin. The sera of hay-fever, urticarial, and eczematous patients only occasionally transfer this reaction. This failure is ascribed to a relatively low antibody content in such sera and to the limitations of the technic used.
A Quick Method for Preparing Homogeneous Suspensions of Hemolytic Streptococcus Antigens for Agglutination Testing
Authors: Spicer Sophie
Published: December 2022

It is well known that the greatest single difficulty encountered in the application of the agglutination and agglutinin absorption tests to the hemolytic streptococcus, is the fact that the hemolytic streptococcus almost invariably grows in liquid media, with sedimentation of the cells, leaving at the end of eighteen to twenty-four hours incubation, a clear supernatant fluid, whereas a cloudy homogeneous suspension of cells is essential for the agglutination test.

The belief that the spontaneous clumping of the streptococci in broth media is due to excessive acidity produced during the growth of the bacteria brought about the adaptation of special methods of growing these organisms. One of the methods is to cultivate the organisms in calcium-carbonate-glucose broth in which the carbonate is supposed to neutralize the acidity in the broth culture. Another method, developed by Dochez, Avery and Lancefield, depends on the use of a special sugar-free broth containing buffer. The buffer used is dibasic potassium phosphate.
A Study of the Comparative Value of Rough and Smooth Strains of B. Typhosus in the Preparation of Typhoid Vaccines
Authors: Grinnell Francis B.
Published: December 2022

That prophylactic vaccination has been of the greatest value in reducing the incidence of typhoid fever, especially in military organizations under war conditions, as well as in times of peace, can hardly be questioned. The instances, however, of failure of such vaccination to protect against ordinary exposure to typhoid are sufficiently frequent to suggest that the present procedure is open to improvement.

A number of writers (1) have, on the basis of active and passive protection experiments with laboratory animals, and also on theoretical grounds, pointed out the probable importance of selecting smooth, virulent strains of the organisms used in preparing the vaccines. Larkum (2) obtained six strains of B. typhosus “Rawlins” used by different laboratories in the preparation of vaccines and found that five of them were non-virulent rough strains.
Protection Against Fatal Anaphylactic Shock with γ-Globulins in Guinea Pigs and Mice
Authors: Halpern Bernard N. , Frick Oscar L.
Published: December 2022

The effects of γ-globulins originating from various animal species on fatal anaphylactic shock induced by passive sensitization have been investigated in guinea pigs and mice.

Human and rabbit γ-globulins completely protected guinea pigs against fatal anaphylactic shock when injected in adequate doses before or simultaneously with sensitization. However, γ-globulin was injected after passive sensitization, the protective effect decreased when the interval between sensitization and injection of γ-globulin was increased.

A similar effect of human γ-globulin was observed in Haemophilus pertussis-treated and passively sensitized mice.

The quantity of γ-globulin required to prevent fatal anaphylaxis was much higher in mice than in guinea pigs.

Horse and bovine γ-globulins were ineffective even in very high doses.

The significance and the possible mechanism of action of the γ-globulins are discussed.
Studies on Simian Virus 40
Authors: Meyer Harry M. , Hopps Hope E. , Rogers Nancy G. , Brooks Barbara E. , Bernheim Barbara C. , Jones William P. , Nisalak Ananda , Douglas Robert D.
Published: December 2022

Simian virus 40 or vacuolating virus infection, in our experience as in that of others, is common in rhesus monkeys and uncommon in Cercopithecus monkeys that reach laboratories in this country. Cynomolgus monkeys resemble the Cercopithecus in this respect. The infection rate in laboratory rhesus has been high for a number of years, at least since 1953.

Experimental infection of Cercopithecus monkeys with SV40 by intranasal instillation results in viremia but no apparent illness; virus also appears in the nasopharyngeal secretions and in the feces. Susceptible monkeys contract infection when intimately exposed to those that are excreting virus.

A positive correlation exists between complement-fixing and neutralizing antibodies against SV40 in the sera of monkeys. Hence, in most serologic studies the more rapid complement fixation test may be substituted for the neutralization test.

Serologic tests serve as a guide in selecting SV40-free monkeys whose kidneys are to be used for the preparation of cell cultures. Animals with antibodies are likely to provide contaminated tissues. On the other hand, monkeys which remain free of antibodies for a number of weeks while maintained under isolation conditions should provide tissues which do not yield SV40 in cell cultures.

The multiplication of SV40 in primary cell cultures prepared from Cercopithecus monkey kidney, in continuous line cells obtained from the same source (BS-C-1) and in rhesus continuous cell culture (LLC-MK2) has been studied. The observations provide information on the time of appearance of cytopathogenic changes following inoculation of different amounts of virus, and the relation of the level of virus in the culture to presence of recognizable CPE and detectable complement-fixing antigen.

Cultures of a continuous cell line (BS-C-1) developed from Cercopithecus kidney tissue are fully as susceptible to SV40 as are primary Cercopithecus kidney cell cultures. A stable line of rhesus kidney cells sustains the growth of SV40, develops cytopathogenic changes after prolonged incubation, but without the characteristic vacuolation produced by this agent in Cercopithecus cells and produces complement-fixing antigen. However, the rhesus stable line lacks the exquisite sensitivity of the continuous Cercopithecus line in detecting minute amounts of virus.
The ultrasound use of simulators, current view, and perspectives: Requirements and technical aspects (WFUMB state of the art paper)
Authors: Dietrich Christoph F. , Lucius Claudia , Nielsen Michael Bachmann , Burmester Eike , Westerway Susan Campbell , Chu Chit Yan , Condous George , Cui Xin-Wu , Dong Yi , Harrison Gill , Koch Jonas , Kraus Barbara , Nolsøe Christian Pállson , Nayahangan Leizl Joy , Pedersen Malene Roland V. , Saftoiu Adrian , Savitsky Eric , Blaivas Michael
Published: December 2022

Simulation has been shown to improve clinical learning outcomes, speed up the learning process and improve learner confidence, whilst initially taking pressure off busy clinical lists. The World Federation for Ultrasound in Medicine and Biology (WFUMB) state of the art paper on the use of simulators in ultrasound education introduces ultrasound simulation, its advantages and challenges. It describes different simulator types, including low and high-fidelity simulators, the requirements and technical aspects of simulators, followed by the clinical applications of ultrasound simulation. The paper discusses the role of ultrasound simulation in ultrasound clinical training, referencing established literature. Requirements for successful ultrasound simulation acceptance into educational structures are explored. Despite being in its infancy, ultrasound simulation already offers a wide range of training opportunities and likely holds the key to a broader point of care ultrasound education for medical students, practicing doctors, and other health care professionals. Despite the drawbacks of simulation, there are also many advantages, which are expanding rapidly as the technology evolves.
A cross-sectional study of musculoskeletal disorder and their environmental determinants among cycle rickshaw pullers of Delhi
Authors: Kumar Nitesh , Rasania S. K. , Acharya Anita Shankar , Rasheed Nazish
Published: December 2022

Introduction:

Rickshaw pulling is among the major activities in the informal sector. Cycle rickshaw pulling involves the task of prolonged sitting, fixed posture, and vibrations which could increase the risk of developing many health problems including one of the major problems of musculoskeletal disorder (MSD). Rickshaw pulling remains important for urban transport system, and such activities contribute in terms of employment and transportation services. The injury and illness resulting from work leads to lower productivity and quality employment which force them to increase their daily hours of working. The work environment and various other environmental determinants for MSD were assessed. The spatial variability of these environmental determinants and MSDs of cycle rickshaw pullers was studied in Delhi.

Material and Methods:

A cross-sectional study was conducted among cycle rickshaw pullers of Delhi. Five districts were randomly selected, and out of 448 study subjects, a total of 425 were included in the study. Consent was obtained before the study. The Nordic Musculoskeletal Questionnaire instrument for MSDs was used. The spatial distribution of MSD and risk factors was studied using QGIS software.

Results:

MSD was observed in 51.5% of the cycle rickshaw pullers and the prevalence increased with age from 9.6% to 34.7%. A statistically significant association of MSD with duration of work, sleeping hour, and sleeping place was observed. Poor road condition and posture were also having an association with MSD.

Conclusion:

Every second cycle rickshaw puller was having MSD. Lifestyle, road conditions, harsh environmental condition, strenuous physical exertion, and ergonomics of the cycle rickshaw were important factors contributing for MSD.
Oral health status and oral health related quality of life in Kodhu tribes – A descriptive cross sectional study
Authors: Chatti Prathyusha , Reddy Vamsi Krishna , Parlapalli Vineela , Pydi Siva Kumar , Pallekonda Adithya Teja Prasad , Janapareddy Karishma
Published: December 2022

Introduction:

In this modern era, a significant group of people is living in isolated hilly areas far away from civilization with their custom and beliefs. They are known as “tribes.” “Kodhu” tribe is one of the major Indian tribes present in the remote areas of Visakhapatnam. The objective is to assess the oral health status and oral health-related quality of life and education level in Kodhu Tribe in residing in Araku and Paderu regions of Visakhapatnam.

Material and Methods:

A descriptive cross-sectional study was conducted among the Kodhu tribal population situated in the Araku and Paderu areas Visakhapatnam, Andhra Pradesh. The study comprised of 800 participants selected using a simple random sampling technique. Chi-square test was used to assess the oral health status of the tribal population, while, independent t-test was used for multiple comparison of OHIP-14 and oral health status. A p-value ≤ 0.05 was considered statistically significant.

Results:

Among 800 participants, 458 were illiterate, and 342 were literate. The prevalence of dental caries was 49% among the illiterates while literates had 50.4% prevalence and the difference was statistically significant (P < 0.03). The periodontal status prevalence was found to be higher in illiterates (56.4%). The domains that are present in OHIP were found to be significantly associated with dental caries, periodontal status, and oral mucosal lesions (P < 0.001).

Conclusion:

The oral health status of Kodhu tribe was found to have high prevalence of the periodontal disease and dental caries. Regular oral examination by dental professionals, dental health education, and motivation to maintain oral hygiene should be insisted to improve the oral health status of this tribal community.