bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression, Regulation, and Function of B Cell-Expressed CD154 in Germinal Centers
Authors: Grammer Amrie C. , McFarland Richard D. , Heaney Jonathan , Darnell Bonnie F. , Lipsky Peter E.
Published: December 2022

Activated B cells and T cells express CD154/CD40 ligand in vitro. The in vivo expression and function of B cell CD154 remain unclear and therefore were examined. Tonsillar B and T cells expressed CD154 at a similar density both in situ and immediately ex vivo, whereas a significantly higher percentage of the former expressed CD154. CD154-expressing B cells were most frequent in the CD38positiveIgD+ pre-germinal center (GC)/GC founder, CD38positive GC and CD38−IgD− memory populations, and were also found in the CD38−IgD+ naive and CD38brightIgD+ plasmablast subsets, but not in the CD38brightIgD− plasma cell subset. B cell expression of CD154 was induced by engaging surface Ig or CD40 by signals that predominantly involved activation of AP-1/NF-AT and NF-κB, respectively. The functional importance of CD154-mediated homotypic B cell interactions in vivo was indicated by the finding that mAb to CD154 inhibited differentiation of CD38positiveIgD− GC B cells to CD38−IgD− memory cells. In addition, mAb to CD154 inhibited proliferation induced by engaging sIg or CD40, indicating the role of up-regulation of this molecule in facilitating B cell responsiveness. Of note, CD154 itself not only functioned as a ligand but also as a direct signaling molecule as anti-CD154-conjugated Sepharose beads costimulated B cell responses induced by engaging surface Ig. These results indicate that CD154 is expressed by human B cells in vivo and plays an important role in mediating B cell responses.
Characterization of RNA Binding Proteins Associated with CD40 Ligand (CD154) mRNA Turnover in Human T Lymphocytes
Authors: Rigby W. F. C. , Waugh M. G. , Hamilton B. J.
Published: December 2022

CD154 (CD40 ligand (CD40L)) has been demonstrated to play an essential role in the development of humoral and cellular immunity through its interaction with CD40. While earlier studies have examined the regulation of CD154 expression by transcriptional and posttranslational pathways, scant data exist on its regulation at a posttranscriptional level. In this report we demonstrate that CD154 mRNA is rapidly turned over in primary culture of activated human T lymphocytes. Moreover, we demonstrate that CD154 mRNA is unstable, but can be stabilized by treatment with either phorbol esters or calcium ionophores. To address this lability of CD154 mRNA, we examined the ability of cytoplasmic proteins to bind to its 3′ untranslated region (3′UTR). Two major proteins (p25 and p50) capable of binding the 3′UTR of CD154 were identified. The p25 binding activity was associated with polysomes and appeared to correlate with CD154 mRNA instability. Intriguingly, these proteins did not appear to bind to the AU-rich elements present in the 3′UTR of CD154. Rather, their binding was localized to unique sites between nt 471–811 of the 3′UTR, which lack any classical AU-rich elements. These data suggest that these proteins interact with distinct cis-acting elements that are important in the posttranscriptional regulation of CD154 expression. As such, identifying these proteins will help us understand the signals that are necessary for CD154 expression by activated T cells.
Failure of Rearranged TCR Transgenes to Prevent Age-Associated Thymic Involution
Authors: Lacorazza H. Daniel , Guevara Patiño Jose A. , Weksler Marc E. , Radu Dorel , Nikolić-Z̆ugić Janko
Published: December 2022

After puberty, the thymus undergoes a dramatic loss in volume, in weight and in the number of thymocytes, a phenomenon termed age-associated thymic involution. Recently, it was reported that age-associated thymic involution did not occur in mice expressing a rearranged transgenic (Tg) TCRαβ receptor. This finding implied that an age-associated defect in TCR rearrangement was the major, if not the only, cause for thymic involution. Here, we examined thymic involution in three other widely used MHC class I-restricted TCRαβ Tg mouse strains and compared it with that in non-Tg mice. In all three TCRαβ Tg strains, as in control mice, thymocyte numbers were reduced by ∼90% between 2 and 24 mo of age. The presence or absence of the selecting MHC molecules did not alter this age-associated cell loss. Our results indicate that the expression of a rearranged TCR alone cannot, by itself, prevent thymic involution. Consequently, other presently unknown factors must also contribute to this phenomenon.
Up-Regulation of NK Cytotoxic Activity Via IL-15 Induction by Different Viruses: A Comparative Study
Authors: Fawaz Lama M. , Sharif-Askari Ehsan , Menezes José
Published: December 2022

IL-15 is a recently identified cytokine that belongs to the four α-helix bundle cytokine family and possesses biological activities similar to those of IL-2. Its ability to induce effectors of NK activity suggests its involvement in innate immunity. In this study, we analyzed the effect of different viruses (HSV, EBV, respiratory syncitial virus, vesicular stomatitis virus, influenza virus, reovirus, and Sendai virus) on the up-regulation of NK activity in vitro. Exposure of human PBMC to the these viruses resulted in an immediate up-regulation of NK activity of PBMC via IL-15 induction; this effect was abrogated in the presence of mAbs to IL-15. Results of experiments conducted in parallel using mAbs to IL-15, as well as to other cytokines (IL-2, IL-12, IFN-γ, and TNF-α), clearly indicated that IL-15 was specifically responsible for the observed effect. Furthermore, supernatants of virus-infected PBMC cultures significantly enhanced NK activity of uninfected PBMC in vitro. An increase of IL-15 protein levels 20 h postinfection was also confirmed in a bioassay using the IL-2-dependent cell line CTLL. Kinetic analysis of IL-15 mRNA expression using a semiquantitative RT-PCR revealed that the level of IL-15 messages peaked at different time points (up to 12 h) postinfection, depending on the nature of the virus. Taken together, these results suggest that the IL-15 response of the host to viral infection and the subsequent NK cell activation represent an important effector mechanism of the innate immune surveillance of the host against viral infections.
Ectosomes Released by Human Neutrophils Are Specialized Functional Units
Authors: Hess Christoph , Sadallah Salima , Hefti Andreas , Landmann Regine , Schifferli Jürg-Alfred
Published: December 2022

Here we show that human polymorphonuclear leukocytes (PMN) release ectosomes independently of complement attack during their activation both in vitro and at the site of inflammation in vivo. Patterns of biotinylated proteins on the surface of PMN and on PMN-derived ectosomes indicated a specific sorting of cell surface proteins into and out of ectosomes. Ectosomes expressed clusters of complement receptor 1 (CR1), which allowed them to bind efficiently to opsonized bacteria. Myeloperoxidase and human leukocyte elastase, both stored within the azurophilic granules of PMN, were found to colocalize on ectosomes with CR1. Furthermore, myeloperoxidase colocalized with human leukocyte elastase. In contrast, not present on CR1-expressing ectosomes were CD63, a selective marker for the azurophilic granules, and CD14, which is located within the same granules and the secretory vesicles as CR1. Of the other complement regulatory proteins expressed by PMN, only CD59 colocalized with CR1, while CD55 and CD46 were almost absent. Ectosomes released by activated PMN at the site of inflammation may function as a well organized element (ecto-organelle), designed to focus antimicrobial activity onto opsonized surfaces.
Normal Induction of Oral Tolerance in the Absence of a Functional IL-12-Dependent IFN-γ Signaling Pathway
Authors: Mowat Allan McI. , Steel Margaret , Leishman Andrew J. , Garside Paul
Published: December 2022

There is considerable evidence that regulatory cytokines play an important role in mediating the systemic tolerance found after oral administration of protein Ags. Although most existing work has focused on cytokines such as IL-4, IL-10, and TGF-β, recent evidence from TCR transgenic systems suggests that the induction of oral tolerance is accompanied by priming of Ag-specific IFN-γ production. IFN-γ has also been implicated as a mediator of T cell tolerance in other models in vivo and in vitro, including that induced by aerosol administration of protein. We show here that feeding tolerogenic doses of OVA primes for IFN-γ production in the spleen of mice with a normal T cell repertoire. However, depleting IFN-γ at the time of feeding OVA had no effect on the induction of tolerance. In addition, tolerance was induced normally in both IFN-γ receptor knockout (IFN-γR−/−) and IL-12 p40 knockout (IL-12−/−) mice. This was the case for all components of the systemic immune response and also with a variety of feeding protocols, including those believed to induce distinct regulatory mechanisms. We conclude that IL-12-dependent IFN-γ-mediated regulation does not play an essential role in oral tolerance.
Defective CD8+ T Cell Activation and Cytolytic Function in the Absence of LFA-1 Cannot Be Restored by Increased TCR Signaling
Authors: Shier Peter , Ngo Karen , Fung-Leung Wai-Ping
Published: December 2022

Signaling through the TCR as well as engagement of costimulatory molecules are required for efficient T cell activation and progression into differentiated effector cells. The β2 integrin LFA-1 (CD11a/CD18) has been implicated in TCR costimulation as well as in cell-cell adhesion function, but its exact role is still ambiguous. The present study focuses on the requirement for LFA-1 in CD8+ T cell activation and effector function using LFA-1-deficient cells expressing the 2C transgenic TCR as a model system. The lack of LFA-1 expression in 2C T cells resulted in severely diminished proliferative response toward allogeneic BALB/c splenocytes. Increase in TCR signaling alone by pulsing stimulators with high affinity peptides, p2Ca or QL9, had minimal effects in restoring proliferation. Addition of exogenous IL-2, however, enhanced the effect of peptide pulsing on proliferation of LFA-1-deficient 2C T cells. LFA-1-deficient 2C CTLs generated from alloantigen stimulation exhibited a defective cytotoxic activity when tested on a variety of target cells. Cytolysis could be improved, but not fully rectified by peptide pulsing of target cells. Thus, in the 2C TCR model, LFA-1 has a requisite role for optimal CD8+ T cell activation and effector function, which cannot be overcome by increasing peptide/MHC density on either the APCs or target cells, respectively.
Influence of Lymphocytes on the Presence and Organization of Dendritic Cell Subsets in the Spleen
Authors: Crowley Mary T. , Reilly Christina R. , Lo David
Published: December 2022

Studies were undertaken to clarify the roles of individual leukocyte populations in maintaining the presence and organization of splenic dendritic cells (DCs). Using Abs specific for DC subsets, we found that the distinct types of DC maintained appropriate compartmentalization within the white pulp of lymphocyte-deficient mice despite an unusual overall distribution of DCs. Even in mice lacking both B and T lymphocytes, the central arteriole remained the structure around which T area DCs were organized. Marginal zone area DCs remained in a peripheral sheath excluded from the T area DCs. Additionally, we revealed an important role for splenic B cells in the presence and organization of marginal zone cells. B-deficient or B- and T-deficient mice lacked sialoadhesin+ marginal zone macrophages and lacked MAdCAM-1 expression in marginal zone reticular endothelial cells. Adoptive transfer of B lymphocytes induced MAdCAM-1 expression but failed to recruit marginal zone macrophages. Taken together, our results demonstrate that the arrival, localization, and persistence of DCs in spleen are events not solely dependent upon signals from the mature B and T cells or marginal zone macrophages. We suggest that specific stromal elements in the vicinity of the central arteriole are primarily responsible for providing directional cues to the DC.
A Novel Role for H-Ras in the Regulation of Very Late Antigen-4 Integrin and VCAM-1 Via c-Myc-Dependent and -Independent Mechanisms
Authors: Liu Zhao-Jun , Tanaka Yoshiya , Fujimoto Hiroko , Mine Shinichiro , Morinobu Akio , Yagita Hideo , Okumura Ko , Oishi Isao , Udagawa Jun , Yamamura Hirohei , Minami Yasuhiro
Published: December 2022

Despite extensive studies on the crucial functions of Ras and c-Myc in cellular proliferation and transformation, their roles in regulating cell adhesion are not yet fully understood. Involvement of Ras in modulating integrin activity by inside-out signaling has been recently reported. However, in contrast to R-Ras, H-Ras was found to exhibit a suppressive effect. Here we show that ectopic expression of a constitutively active H-Rasv12, but not c-Myc alone, in a hemopoietic cell line induces activation of very late Ag-4 (VLA-4, α4β1) integrin without changing its surface expression. Intriguingly, coexpression of H-Rasv12 and c-Myc in these cells results in not only the activation of VLA-4, but also the induction of expression of VCAM-1, the counterreceptor for VLA-4, thereby mediating a marked homotypic cell aggregation. In addition, H-Rasv12-induced VLA-4 activation appears to be partly down-regulated by coexpression with c-Myc. Our results represent an unprecedented example demonstrating a novel role for H-Rasv12 in the regulation of cell adhesion via c-Myc-independent and -dependent mechanisms.
The Antigenic Substances of the Tubercle Bacillus
Authors: Dienes L.
Published: December 2022

Guinea pigs sensitized with killed bacteria compared with infected guinea pigs give relatively stronger reactions with the protein substances extracted with weak NaOH from the bacillary bodies than with the filtrate of broth culture.

When groups of tuberculous guinea pigs are treated with different tuberculin preparations with different antigen specificity the skin reactions in each group (compared to the reaction of the other groups) are relatively slighter with the preparations used for the treatment than with the other preparations. These observations show that between different tuberculin preparations not only quantitative, but also qualitative differences are present with respect to the tuberculin effect.

Of our purified preparations only the protein substances have had tuberculin effect, and these preparations with few exceptions have also had antigenic properties in vitro. Two of the important tuberculin preparations, the protein substances precipitable at low pH, and the tuberculin-active substances of the broth, nonprecipitable with acids, gave reaction only with a few of our sera.

The tuberculin effect probably is one of the several manifestations of the specific properties of the antigens.
Anaphylaxis
Authors: Bally L. H.
Published: December 2022

Although the literature on the effects of histamine is quite extensive it deals mostly with observations made upon dogs and cats, while observations upon reactions produced in the rabbit are particularly conspicuous by their absence. Possibly this is due to one of the peculiar anomalies of histamine in failing to produce an immediate depressor effect in rodents as it does in carnivora. This has been quite puzzling since histamine is known to be a strong stimulant of plain muscle, yet produces a pronounced fall in blood pressure of carnivora, apparently due to capillary dilation. In the rabbit the exact opposite reaction occurs—a rise in blood pressure, presumably due to vasoconstriction as one would expect.

Dale and Richards (1) point out that vasodilator effects of histamine are purely peripheral effects upon the blood vessels, independent of any nervous connection. They conclude that the vasodilation is due to the relaxation of the tone of the capillaries since histamine has a constrictor effect upon the arteries.
Anaphylaxis
Authors: Bally L. H.
Published: December 2022

Among immunologists the rabbit has enjoyed considerable popularity as an experimental animal, but for some unknown reason has not been used in anaphylactic studies as extensively as some other animals—dogs and guinea pigs. This situation has probably been fostered by statements and inferences in the literature that the rabbit is very difficult to sensitize, and that the usual criteria used to denote sensitization among other species give rather variable and inconclusive results when applied to the rabbit.

Auer (1) states that rabbits are not so easily prepared, nor can as high a degree of sensitization be obtained as readily and as certainly as in the guinea pig. He suggests that of various methods employed to sensitize rabbits, perhaps some modification of the Arthus method—4 to 8 injections of antigen subcutaneously 4 to 8 days apart—is the best. He also quotes Arthus as finding the incubation period from 8 to 15 days after the last injection.
A Method for Comparison of Antipneu-Mococcus Sera
Authors: Goodner Kenneth
Published: December 2022

A simple method for the comparison of the curative properties of antipneumococcus serum has been described, and the value of such a method discussed.
The Examination of 2,433 Human Sera for Agglutinins of Brucella Abortus
Authors: Welsh M. F.
Published: December 2022

During the winter months of 1926–27 this Laboratory through the courtesy of the Maryland State Board of Health, was able to test 2,433 human sera for reactions against a Brucella abortus antigen by the agglutination method. The sera had been sent in for routine Wassermann examination, from various parts of the Satate.

In this series of tests, Myer's strain no. 80 of Br. abortus was used. The cultures were grown on agar slants having a pH of about 6.8. These were incubated at 37°C. for forty-eight hours and then washed off with about 10 cc. of phenolized physiological salt solution. The heavy suspension of organisms resulting was filtered through a thin layer of sterile cotton to remove any foreign material present. The filtrate was stored as a stock antigen at about 15°C. and examined occasionally for purity. For test purposes, the stock antigen was diluted with phenolized physiological salt solution until the turbidity corresponded with the no. 1 tube of McFarland's nephelometer.
Studies in Hypersensitiveness
Authors: Cooke Robert A. , Spain W. C.
Published: December 2022

Introduction The hypersensitive state in man, which is clinically expressed as asthma and hay fever, though studied now for nearly twenty years is by no means fully understood. We do not yet know exactly how and why a sensitiveness to one or several particular substances originates and persists in a certain small percentage (about 5 per cent) of the human race.

The condition was originally assumed to be anaphylaxis (1) (2), but early studies (3) in asthma and hay fever disclosed facts regarding this type of sensitization in man that were not in entire accord with those that obtain in anaphylaxis. Briefly stated, these facts were: that inherited factors play an important part for they influence the age of onset of clinical sensitization as well as the number to become sensitive among the offspring of sensitive antecedents; that the condition is apparently spontaneous, since clinical sensitization is not obtained by artificial means.
Further Experiments on the Agent of Herpes
Authors: Zinsser Hans , Tang Fei-Fang
Published: December 2022

In working on the neutralizing powers of the serum of rabbits immunized against the agent of herpes, the writers noticed some years ago (1) that salt solution suspensions of this material taken from the brains of rabbits dead of the disease rapidly lost virulence, upon incubation at 37.5°C. There was a distinct diminution of infectiousness within two or three hours, and often complete loss of virulence within five or six hours, the time period varying with the densities of the suspensions. Suspensions in which the amount to be inoculated into a rabbit (0.1 to 0.25 cc.) contained not more than three or four fatal doses—that is, dilutions of 1:16,000 according to the potency of the virus—were often completely inactivated within four or five hours, whereas heavier suspensions would last correspondingly longer, probably because of the presence of minute particles of brain material within which the herpetic agent was protected to some extent from the deteriorating influences active in the salt solution.
The Dick Test and Allergic Skin Reactions to Streptococcus Nucleoproteins
Authors: Ando K.
Published: December 2022

There are those who believe that the specific poison of Streptococcus scarlatinae, though thermostable, is a soluble toxin comparable to that of diphtheria, and there are others who hold that it is endotoxic in nature (especially Duval and Hibbard); correspondingly, there is a conflict of opinion as to the nature of Dick reaction. According to the prevalent opinion, the Dick test indicates the presence or absence of antitoxin to the scarlatinal toxin, but there are also a few who still believe in the allergic nature of Dick reaction (v. Gröer, Dochez, Cooke, Bristol etc.). In examining the purification and concentration of the Dick toxin, we have recently succeeded in isolating two substances with which skin reactions can be elicited in human beings. The first seems to be bacterial protein, which may be considered as the so-called nucleoprotein and the second as the essential specific toxin which is heat-labile and exotoxic in nature.
Some Cellular Reactions and Immunity in Tuberculosis
Authors: Sherwood Marion B.
Published: December 2022

Inasmuch as tuberculosis occurs and becomes progressive in both allergic animals and those of primary infection, despite the fact that in both the tubercule bacilli are ingested by the polymorphonuclear leucocyte, it has long been believed that the polymorphonuclear cell serves merely as a vehicle for the transport of the organisms throughout the body. That this view is still held is clearly shown by certain statements made in the recently published Tuberculosis in Man and Animals by Calmette (1). An increasing number of publications, particularly abundant during the past few years, suggest that this theory should not go unchallenged. The various papers of Sabin and her co-workers (2) are particularly pertinent in this connection. These contributions have dealt with the cytology of the fluids of the animal body and have considered not only the cellular picture in the normal animal but also the changes following the inoculation of various substances.
Variation in Susceptibility to Diphtheria Toxin Among Guinea Pigs and Rabbits and Accuracy of Various Methods of Toxinantitoxin Titration
Authors: Ando K. , Nishimura H.
Published: December 2022

The sensitiveness of the skin of guinea pigs and rabbits to a small amount of diphtheria toxin shows considerable variation locally and individually. The skin of the side-chest and flank gives a uniform and more marked reaction to the injection of a small amount of diphtheria toxin than the skin of the abdomen. Abnormally low skin sensitiveness to diphtheria toxin is an indication of antitoxin content in the blood serum. We propose to define the term “susceptibility” as follows: Susceptibility is expressed by the m.l.d. of one toxin determined with guinea pigs of average susceptibility divided by the m.r.d. of the same toxin on the guinea pig or rabbit tested. The introduction of this idea of susceptibility would yield more accurate experimental results in regard to the assay of toxin and antitoxin. Individual variation in susceptibility to diphtheria toxin among guinea pigs was considerable, and the susceptibility varied from 2000 to 75 in our tests with almost 300 guinea pigs. Normal susceptibility seems to be from 1000 to 500. The susceptibility to diphtheria toxin of rabbits varied from 3000 to 500 in our tests with 30 rabbits. Pregnancy and littering seem temporarily to reduce very much the skin sensitiveness to diphtheria toxin. The m.r.d. and the Lr/500 dose of a given toxin showed considerable variation according to the varying susceptibility of the guinea pig employed for titration. The Roemer method of toxin-antitoxin titration, therefore, must be conducted as follows: the m.r.d. or the Lr/500 dose of a given toxin is determined from the ratio of the m.r.d. or the Lr/500 dose of test toxin to that of a standard toxin tested on the same guinea pig, at the same time. Male guinea pigs over 400 grams weight are preferable as test animals for the intracutaneous method. By the Schick test we are enabled to discover the guinea pig of abnormal susceptibility which might cause irregularities in the result of the determination of m.l.d. of a diphtheria toxin. Individual variation of susceptibility among guinea pigs might have some influence on the determination of the “Immunity index.”
Further Studies on Heterophilic Antibodies in Serum Sickness
Authors: Davidsohn I.
Published: December 2022

Eighty-three patients were treated with normal horse serum or horse immune sera. Twenty-seven had agglutinins for sheep cells before the treatment. Of the fifty-six remaining, all but five developed agglutinins for sheep red blood cells in titers from 1:4 upward. The five negative cases were apparently tested too early or too late following treatment. Many of the cases showed a very marked increase of their sheep hemolysin titer. In a control series of 810 normal cases 9 per cent agglutinated sheep red cells in a dilution of 1:4, and the highest titer for the hemolysin for sheep cells was 1:128 in a very small number of cases (six of 381), the highest titer in most sera being 1:16. All forty-five patients who developed serum sickness showed agglutinins and many a very high hemolysin for sheep blood. The agglutinins were present at the onset of the disease whenever the blood was then obtained. In a series of 6 cases, they appeared in each of them before the onset of the initial symptoms, the intervals being six hours to eight days. The average titers for the agglutinins and hemolysins were very much higher in the cases who have had serum sickness than in those who did not have it. The difference is so marked that a hemolysin titer of 1:128 or higher and an agglutinin titer of 1:32 or higher is suggestive of serum sickness in a more or less recent past. Of ten patients who developed an immediate or accelerated reaction, eight had agglutinins before the injection of the serum, and the two remaining showed them three days after the injection. The incidence of immediate or accelerated reactions was 30 per cent among patients with agglutinins before the injections of the horse sera, and only 5 per cent among those without agglutinins before the injection. Three out of four patients, who reacted with a late local reaction, had agglutinins demonstrable in a dilution 1:4 before the injection. Only one of the patients responding with an immediate or accelerated reaction, and none of those responding with local reactions developed serum sickness. There seems to be a relation between the pre-existence of agglutinins for sheep cells before the injections of horse sera and the type of reaction. The rôle of the agglutinins may be merely that of an indicator of some changes predisposing for such type of reactions. Agglutinins for ox blood are normally present in a relatively high percentage of cases, and when absent they frequently appeared in immunized patients after the onset of serum sickness. Agglutinins for guinea pig red cells are present in a very large number of normal sera, and almost all sera agglutinate rabbit blood cells. This gives the agglutinins for sheep blood a unique significance.
Vaccinia: Studies of Immunity, Reactions and Effects of Heat
Authors: Andervont H. B. , Rosenau M. J.
Published: December 2022

Pirquet (3) and Force (4) mention a reaction following the introduction of vaccine virus heated to 80°C. into the skin of previously vaccinated persons. This was noted during the course of experiments in which heated material served as “control” for unheated virus. Our experiments confirm their findings as regards the appearance of a reaction with heated virus and also indicate that with the single scratch method of vaccination, virus heated to 70°C. for one hour, kept in boiling water for one hour, autoclaved for one hour or kept at room temperature for five years is capable of eliciting the response in previously vaccinated individuals; in fact, our experience teaches that the reaction following the use of heated virus is as constant as that observed when unheated virus is employed. The reaction to heated virus appears and disappears somewhat earlier than the reaction to unheated virus. The heated virus produces a reaction with papules indistinguishable from the well known immediate reaction.

We found also that no reaction occurs when heated virus is used to vaccinate previously unvaccinated children or adults, and that such vaccination induces no immunity.

So far as studies concerning the antigenic substance responsible for the immediate reaction are concerned, our observations tend to show that the virus is the causative factor. An extract of vaccine pulp freed of virus by filtration is incapable of causing the reaction. Furthermore, individuals immunized against cowpox by vaccination with calf virus give the immediate reaction when revaccinated with vaccine virus derived from rabbit brain. These results indicate a common antigen in calf and rabbit material. The vaccine virus is known to be present in both. The possibility of another antigenic substance being responsible is excluded because normal calf skin or glycerinated normal rabbit brain fail to evoke any reaction in previously vaccinated persons.
A Case of Pel Ebstein's Syndrome of Tuberculous Origin
Authors: L'Esperance Elise S.
Published: December 2022

Among the various clinical types of Hodgkin's disease, there is a rather rare form in which gradual splenic enlargement with intermittent attacks of pyrexia, lasting for two weeks or longer, are the most prominent features, the associated lymph node involvement being either absent or insignificant.

This peculiar syndrome was first described by Murchison in 1871, but received very little attention. Pel, in 1885, described three similar cases as pseudoleukemia. This was followed in 1887 with a detailed report by Ebstein of a new infectious disease. From time to time isolated cases of this form of Hodgkin's disease have been reported by Symmers (1909), Wade (1913), Mellon (1916) and the author (1924).

In the further study of the experimental inoculation of chickens with Hodgkin's nodes, a case of Hodgkin's disease with the Murchison-Pel-Ebstein's syndrome was submitted to me from the Memorial Hospital:

The patient was a young man, twenty-five years of age, from the British West Indies.
The Effect of the Injection of Colloidal Substances on Experimental Typhus Fever
Authors: Reimann Hobart A.
Published: December 2022

Many studies have been made to ascertain the effect of the injection of various colloidal substances on the reticulo-endothelial system particularly in regard to the influence on immunity or on the production of demonstrable immune bodies. It is well known that colloidal substances when injected either intravenously or intraperitoneally are rapidly taken up by the endothelial cells. The whole endothelial system takes part in the process but by far the greatest amounts of the substances are found in the reticulo-endothelial cells of the liver, spleen, lungs, lymph nodes and bone marrow (1) (2). It seemed of interest therefore to observe the effect of the injection of certain colloidal substances on typhus fever, a disease which involves chiefly the endothelial cells.

Typhus fever is characterized by proliferative and degenerative changes in the smaller blood vessels of the skin and viscera (3).
On the Inheritance and Racial Distribution of Agglutinable Properties of Human Blood
Authors: Landsteiner K. , Levine Philip
Published: December 2022

The studies reported substantiate the view that an agglutinable property of human blood detected by an agglutinin present in certain exceptional human sera (“extra agglutinin 1”) is inherited and that its frequency shows a racial difference in the two populations examined. Consequently it must be considered as a constitutional property. The same conclusion seems to hold for other properties of red cells demonstrable by atypical human sera.

Evidence is presented to show that the qualities characterizing the two subgroups of group A are inherited.

The experiments reported were made with the use of some atypical sera containing agglutinins of marked activity.
Distribution of Antibodies in the Serum and Organs of Rabbits
Authors: Freund Jules , Henderson Howard J.
Published: December 2022

The action of bile upon bacteria, toxins and other antigens has been the subject of numerous investigations, for the biliary system is frequently infected and the bile of carriers of typhoid bacilli may contain them for years after the disease has been contracted.

We selected agglutinins for the present inquiry into the antibody content of the bile after immunization because they are the most readily demonstrable antibodies. The reports on agglutinins in the bile are very contradictory. Exhaustive reviews of the literature can be found in the papers of Neilson and Meyer (1) and in the article by Perry (2). Perry immunized dogs with red blood-cells of goat and rat. She did not find specific hemagglutinins in the bile of dogs that had been given a single injection of erythrocytes and had agglutinins in their blood. Neilson and Meyer came to the following conclusion:
The Serologic Diagnosis of Pullorum Disease in Domestic Fowls
Authors: Valley George , Casman E. P.
Published: December 2022

The precipitate obtained in the agglutination tube consists of protein and lipoid fractions. It is suggested that under the conditions (increased H-ion and salt concentration) prevailing in the agglutination tube a lipin-protein complex formed from substances in the serum is precipitated.

Evidence is cited to show that phenol in 0.5 per cent concentration may cause precipitation of certain protein constituents of serum.

It is further indicated that, aside from the metabolic changes accompanying egg laying, such factors as muscular exercise or shock may influence the pH and the lipoid content of the serum and consequently cause “cloudy” reactions.

While the predisposing causes for the “cloudy” reaction undoubtedly arise in the serum, the phenomenon of precipitation is nevertheless profoundly influenced by the conditions prevailing in the agglutination tube.
The Question of the Elimination of Foreign Protein (Egg-White) in Woman's Milk
Authors: Donnally Harry H.
Published: December 2022

Evidence of the elimination in the breast milk of food proteins ingested by lactating women, has been clinical. Stuart's inability to confirm Shannon's experiments and conclusions casts grave doubt upon their validity. Walzer's egg absorption work makes it possible to determine when the lactating mother has unaltered egg protein in her blood stream. This constitutes a valuable guide as to the time to collect the breast milk for the study of its egg content. A human anti-egg serum, such as serum F, once found, is available for a long time, and offers considerable latitude to the experimenter. Among receptive skins moderate differences in reactivity are found. A specific test of great delicacy for egg-white is offered by the site in a reactive skin sensitized by human anti-egg serum of high reagin content. Serum F sites may react to one part of egg-white in ten billion parts of salt solution or breast milk whey. A method for the preparation of concentrated breast milk whey for testing is presented, although its concentration may not be of great importance. The concentrated whey of breast milk obtained after raw egg ingestion, on an empty stomach and without other food, from three of eight women, gave the specific reaction for egg-white greater than the control, in sensitized sites in two normal recipients for each whey. Four recipients were utilized for the tests. By comparison of the skin reactions obtained with the breast milk whey, with those of known dilutions of egg-white, it is estimated that the concentration of egg-white in one of them was one part in a million, and in each of the others one part of egg-white in a billion parts. An unsuccessful attempt was made to sensitize a guinea pig passively to egg-white with 2.5 cc. of serum F intraperitoneally, as shown by the uterine strip method of Dale.
Renaissance of Pre-Ehrlich Immunology
Authors: Manwaring W. H.
Published: December 2022

There is convincing evidence that injected antigens undergo a series of chemical “hybridizations” in animal tissues, and suggestive evidence that the resulting antigen-tissue “hybrids” become semi-permanently “symbiotic” with these tissues, both terms, of course, being used metaphorically. Whether or not these “symbiotic hybrids” are to be regarded as partially homologized antigens, as specifically alienated somatic proteins (30), or as antigen-somatic-protein conjugates can not be predicted from present biochemical knowledge. There is convincing evidence that some of these antigen-tissue “hybrids” have properties simulating those of specific antibodies, but no proof thus far that they are identical with these antibodies. There is, however, no evidence at the present time that there is any other physiological method of specific antibody formation.
Pertussis Toxic Filtrates and Toxin-Vaccines
Authors: Mishulow Lucy , Mowry Isabelle W. , Scott Eleanore B.
Published: December 2022

The work of Shwartzman (1) on toxic filtrates of organisms of which heretofore no specific toxic filtrate had been definitely shown, suggested testing B. pertussis for toxin production. It occurred to us that the failure of all previous attempts to clearly demonstrate a specific pertussis toxin may have been due to a combination of two factors: (a) the method of growing the organisms for toxin production, (b) the method of testing for toxicity.

The present investigation was undertaken with the above two points in view.

We selected two strains of B. pertussis for the experiment. One of them was recently obtained from Bordet and was designated “Bordet,” and the other was one of our old stock strains; both of them were type B.

In our preliminary tests we grew the organisms in the same way as for a vaccine.
Biochemical Studies of Bacterial Derivatives
Authors: Funk Elmer H. , Huntoon F. M.
Published: December 2022

Human tubercle bacillus protein MA-100 was isolated by Masucci and McAlpine (1) in November, 1929, from the filtrate of cultures of the human tubercle bacillus H-37, grown on Long's synthetic culture medium. This medium contains no protein, but contains asparagin as a source of organic nitrogen. All proteins present with various other substances, not medium constituents, therefore, in the filtrate must have been synthesized by the tubercle bacillus.

One of the most important of these substances is a specific polysaccharide, closely associated with the proteins. However, Masucci and McAlpine have been able to isolate not only a protein MA-100 free from the polysaccharide, but to obtain the poly-saccharide free from the protein. The designation MA-100 is given the protein to classify the material with the chart published by Johnson (2).

Only one phase of these investigations; namely, the skin sensitivity of man to this particular human tubercle bacillus protein MA-100, when the protein is introduced intradermally, is dealt with in this communication.
A Study of the Blood Group Distribution among Polynesians
Authors: Nigg Clara
Published: December 2022

The incidence of the four blood groups among 413 fullblooded Hawaiians was found to be as follows: group O, 36.5 per cent; group A, 60.8 per cent, group B, 2.2 per cent, group AB, 0.5 per cent. The A1 agglutinogen was found in 100 per cent of the 237 group A Hawaiian bloods examined for this factor. This incidence is in contrast to 80 per cent found in the white race.
Typhoid Agglutinin Production: The Rôle Dosage, Total Amount of Agglutinogen Injected and Frequency of Inoculation Play
Authors: Behrens C. A. , Keipper C. H.
Published: December 2022

Frequency of injections plays a major rôle in typhoid agglutinin production.

A close relationship exists between the interval of injections and the dose employed.

Total amounts of agglutinogen injected have but little direct influence, however some indirect influences are apparent.

The axiom of frequent stimulation of the body cells of the animal by the use of small doses of agglutinogen and by larger doses as the intervals between inoculations are increased, is emphasized.

Typhoid agglutinins with greatest potencies are produced by injecting 0.1 cc. frequently; 1 cc. less frequently and 5 cc. still less often.

Typhoid agglutinins with high titers are possible with any of the three doses studied; the highest, however, follow the employment of the largest dose.

Typhoid agglutinins of equal potencies are elaborated irrespective of dosage, when inoculations are made every third day.

Increasing the dose with each subsequent injection results in agglutinins with much higher titers than when the reverse is true.

Non-specific agglutinin formation is negligible.

Physical deterioration of the rabbits shows its effect on. agglutinin production.

Comparable results are obtained with various agglutinogens, precipitinogens and lysinogens.
Correlation of the Content in Heterophilic Antibody in Human Serum and the Skin Reaction to Guinea Pig Serum As an Antigen
Authors: Ramsdell Susan Griffith
Published: December 2022

Guinea pig serum, used as a native heterophilic antigen, occasioned skin reactions of the immediate type, with regularity, in a group of individuals with skin disturbances believed to be allergic in nature. In the normal group, this reaction appeared in about half the members. The presence of agglutinin for sheep cells was a regular finding in the allergic group in titers considerably higher than that found in the normal. The hemolysin titers did not vary with the groups. No correlation could be established between the occurrence of a skin reaction to guinea pig serum and the heterophilic antibody titers. Haptene and lecithin suspensions did not occasion a marked reaction in any instance. The sub-maximal response could not be correlated with any other finding. The skin response to guinea pig serum could not be identified as a reaction between human heterophilic antibody and a native heterophilic antigen assumed to be contained in the guinea pig serum.
Antigenic Analysis of Cultures of B. Paradysenteriae and B. Morgani Isolated During an Epidemic of Summer Diarrhea
Authors: Mackenzie G. M. , Batt Louise N.
Published: December 2022

The cultures forming the material for this study were obtained during an outbreak of diarrhea in August and September, 1927, in a small rural community in New York State. There were 10 cases in three families; only two children in the three families had no manifestations of the infection; no adults were affected. The symptoms were diarrhea with blood and mucus in the stools, fever, vomiting, prostration. The duration varied from two days to three weeks. The youngest patient was one year of age; the oldest was fifteen; the intensity and duration of symptoms were less in the older children. Organisms obtained for study were isolated from Endo and eosin methylene blue plates seeded with fresh specimens of stools.1
The Sustained Suppression of Hemolysin Response in Passively Immunized Rats
Authors: Neiders Mirdza E. , Rowley Donald A. , Fitch Frank W.
Published: December 2022

When adult rats were immunized with sheep erythrocytes, the secondary hemolysin response was lower than the primary response. The effect of circulating hemolysin on the rat's response to sheep erythrocytes was investigated. A marked inhibition of the primary hemolysin response in the rat was produced by administering homologous anti-sheep erythrocyte serum 24 hr before the injection of sheep erythrocytes. Significant inhibition of the antibody response occurred with a wide range of doses of antiserum and antigen. Inhibition of the antibody response by antiserum occurred when rats were actively immunized intravenously, intraperitoneally, or intradermally. The presence of circulating hemolysin was necessary to demonstrate the inhibition of the hemolysin response. Unresponsiveness to antigenic stimulation induced by a single passive immunization was sustained if small doses of sheep erythrocytes were injected at weekly intervals. The possible mechanisms responsible for this phenomenon were discussed.
Antigens of Coxiella Burnetii
Authors: Ormsbee Richard A. , Bell E. John , Lackman David B.
Published: December 2022

Dimethylsulfoxide and dimethylacetamide have been shown to be capable of extracting protective antigen from the Ohio 314 (Phase I) strain of Coxiella burnetii but not from the Nine Mile (Phase II) strain. The antigen extracted from either strain by these organic solvents fixes complement in the presence of specific antiserum and is precipitable by specific antiserum. The antigen preparations are markedly less toxic than whole organisms in normal animals and much less reactive in the skin of sensitized guinea pigs and rabbits. Some physical and chemical properties of the extracts are given, and the character of the response in guinea pigs to immunization with antigen preparations made from Phase I and Phase II organisms is described.
Potensi Dan Keabsahan Non-Fungible Token Sebagai Objek Jaminan Fidusia
Authors: Haryadi Putri Azura Hana , Taupiqqurrahman
Published: December 2022

Perkembangan teknologi informasi mendorong hampir seluruh bidang dalam kehidupan masyarakat menjadi sesuatu yang berbentuk digital terutama dalam bidang perdagangan. Saat ini masyarakat lebih memilih sesuatu yang bersifat praktis, cepat, dan efisien sehingga berbagai platform digital digunakan dalam kegiatan sehari-hari. NFT merupakan aset digital yang kepopulerannya meroket beberapa tahun ke belakang ini. Adanya karya pada NFT sudah seharusnya karya NFT tersebut bisa dijadikan objek jaminan fidusia. Permasalahan dalam penelitian ini adalah bagaimana potensi NFT sebagai objek jaminan fidusia serta bagaimana keabsahan NFT apabila dijadikan objek jaminan fidusia. Metode penelitian ini adalah yuridis normatif dengan pendekatan undang-undang. Hasil penelitian ini menyatakan bahwa dalam konteks regulasi, Indonesia sudah memberikan suatu peluang atau potensi NFT sebagai jaminan fidusia yang berasal dari Undang-Undang Hak Cipta. Terdapat regulasi di Indonesia yang berkaitan untuk dijadikan ketentuan apabila menjadikan NFT sebagai jaminan fidusia. Itu menjadi cara agar pembebanan jaminan fidusia pada NFT tetap sesuai dengan ketentuan yang ada dan tidak melanggar hukum. Potensi tersebut perlu dilakukan penambahan regulasi yang lain terkait dengan NFT sebagai objek hak cipta. Selanjutnya, kedudukan NFT sebagai objek jaminan fidusia belum sah secara khusus, begitu pula legalitasnya. Berdasarkan regulasi-regulasi terkait yang sudah berlaku, terlihat potensinya untuk dibuat atau dikembangkan suatu produk hukum sebagai regulasi tambahan baru yang mengatur secara khusus dan terperinci. Dengan begitu, masyarakat dapat memanfaatkan NFT dengan maksimal dan bukan hanya sebagai investasi namun dijadikan hal lainnya seperti objek jaminan. Pemanfaatan NFT perlu diiringi dengan produk hukum dan ketentuan yang mengatur secara khusus untuk memberikan perlindungan dari segi hukum.