bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD34+ Cell-Derived CD14+ Precursor Cells Develop into Langerhans Cells in a TGF-β1-Dependent Manner
Authors: Jaksits Silvia , Kriehuber Ernst , Charbonnier Anne Sophie , Rappersberger Klemens , Stingl Georg , Maurer Dieter 
Published: December 2022

AbstractLangerhans cells (LC) are CD1a+E-cadherin (E-cad)+Birbeck granule+ but CD11b−CD36−factor XIIIa (FXIIIa)− members of the dendritic cell (DC) family. Evidence holds that LC originate from CD1a+CD14− rather than CD14+CD1a− progenitors, both of which arise from GM-CSF/TNF-α-stimulated CD34+ stem cells. The CD14+CD1a− progenitors, on the other hand, can give rise to a separate DC type characterized by its CD1a+CD11b+CD36+FXIIIa+E-cad−BG− phenotype (non-LC DC). Although GM-CSF/TNF-α are important for both LC and non-LC DC differentiation, TGF-β1 is thought to preferentially promote LC development in vitro and in vivo. However, the hemopoietic biology of this process and the nature of TGF-β1-responsive LC precursors (LCp) are not well understood. Here we show that CD14+ precursors in the presence, but not in the absence, of TGF-β1 give rise to a progeny that fulfills all major criteria of LC. In contrast, LC development from CD1a+ progenitors was TGF-β1 independent. Further studies revealed that CD14+ precursors contain a CD11b+ and a CD11b− subpopulation. When either subset was stimulated with GM-CSF/TNF-α and TGF-β1, only CD14+CD11b− cells differentiated into LC. The CD11b+ cells, on the other hand, acquired non-LC DC features only. The higher doubling rates of cells entering the CD14+ LCp rather than the CD1a+ LCp pathway add to the importance of TGF-β1 for LC development. Because CD14+CD11b− precursors are multipotent cells that can enter LC or macrophage differentiation, it is suggested that these cells, if present at the tissue level, endow a given organ with the property to generate diverse cell types in response to the local cytokine milieu.
CD44-Deficient Mice Develop Normally with Changes in Subpopulations and Recirculation of Lymphocyte Subsets
Authors: Protin Ursula , Schweighoffer Tamas , Jochum Wolfram , Hilberg Frank 
Published: December 2022

Abstract
Cell adhesion molecules are considered to be pivotal elements required for proper embryo development. The transmembrane glycoprotein CD44, which is expressed in numerous splice variants on the surface of many different cell types and tissues, has been suggested to be involved in several physiological processes such as cell-cell interactions, signal transduction, and lymphocyte homing and trafficking during embryogenesis and in the adult organism. Some splice variants are thought to play an important role in tumor progression. To investigate the physiological roles of CD44 in vivo, we abolished expression of all isoforms of CD44 in mice by targeted insertion of a lacZ/neo cassette into the reading frame of the leader peptide. CD44-deficient mice are viable without obvious developmental defects and show no overt abnormalities as adults. However, CD44-deficient lymphocytes exhibit impaired entry into the adult thymus, although lymphocyte development is apparently unaltered. Our data indicate that all splice variants of CD44 are dispensable for embryonic development and implicate a critical function for CD44 in lymphocyte recirculation.
Quantitative Alleles of CR1: Coding Sequence Analysis and Comparison of Haplotypes in Two Ethnic Groups
Authors: Xiang Lianbin , Rundles Jennifer R. , Hamilton Derrick R. , Wilson James G. 
Published: December 2022

AbstractThe quantitative expression of complement receptor type 1 (CR1) on erythrocytes is regulated by two CR1 alleles that differ in having genomic HindIII fragments of either 7.4 or 6.9 kb and that determine high (H allele) or low (L allele) CR1 expression, respectively, across a 10-fold range. To investigate whether the product of the L allele may contain amino acid substitutions that make it more susceptible to proteolysis, cDNA sequence spanning the CR1 coding region was analyzed in two donors who were homozygous for the H and L alleles and differed by 7-fold in their mean numbers of CR1 per erythrocyte. Sequence differences were detected at 10 nucleotide positions, including 6 that would cause amino acid substitutions. The HindIII RFLP and 3 of the latter 6 sites were analyzed in genomic DNA of 85 Caucasians and 75 African Americans; sites encoding the other amino acid substitutions were analyzed less extensively. Two major haplotypes defined prototypic H and L alleles in both ethnic groups, suggesting that these alleles existed before the African and European populations diverged. Decreased erythrocyte CR1 expression is associated with impaired clearance of immune complexes from blood. Persistence of the L allele in all populations that have been analyzed may suggest a compensatory survival advantage, perhaps related to malaria or another infectious disease.
Molecular Defects in Variant Forms of Mannose-Binding Protein Associated with Immunodeficiency
Authors: Wallis Russell , Cheng Jason Y. T. 
Published: December 2022

AbstractDistinct molecular mechanisms underlying immunodeficiency caused by three different naturally occurring point mutations within the collagen-like domain of human mannose-binding protein (MBP; also known as mannose-binding lectin) have been revealed by introduction of analogous mutations into rat serum MBP. The change Arg23→Cys results in a lower proportion of the large oligomers most efficient at activating the complement cascade. The presence of cysteine at position 23, which forms aberrant interchain disulfide bonds, causes disruption of the normal oligomeric state. The deficiency in MBPs containing Gly25→Asp and Gly28→Glu substitutions also results in part from reduced formation of higher oligomers. However, decreased ability to interact with downstream components of the complement cascade due to changes in both the N-terminal disulfide-bonding arrangement and the local structure of the collagenous domain make more important contributions to the loss of activity in these mutants.
Recombinant Human (rh)IL-4-Mediated Apoptosis and Recombinant Human IL-6-Mediated Protection of Recombinant Human Stem Cell Factor-Dependent Human Mast Cells Derived from Cord Blood Mononuclear Cell Progenitors
Authors: Oskeritzian Carole A. , Wang Zhiliang , Kochan Jarema P. , Grimes Margaret , Du Zhongmin , Chang Hyeun-Wook , Grant Steven , Schwartz Lawrence B. 
Published: December 2022

AbstractAlthough stem cell factor (SCF) appears to be the major growth factor for human mast cells, other factors undoubtedly play important roles in the development, survival, and function of these cells. The current study examined the effects of recombinant human (rh) IL-4 and rhIL-6 on rhSCF-dependent development and survival of human mast cells derived in vitro from cord blood progenitor cells. After 4–8 wk of culture with rhSCF and various amounts of rhIL-4, a dramatic decline in mast cell numbers was observed with rhIL-4, the EC50 being about 0.1 ng/ml. Numbers of other cell types remained high. Mast cells derived from cord blood progenitors after 7 wk of culture with rhSCF alone displayed an MCT phenotype and expressed Kit, FcεRI, and IL-4R on their surface. Mast cells examined after purification by immunomagnetic sorting became apoptotic within hours after exposure to rhIL-4, a phenomenon blocked by anti-IL-4 Ab. Because rhIL-4-dependent apoptosis but not the loss of mitochondrial membrane potential was prevented by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-(Z-VAD)-fluoromethylketone, mitochondrial perturbation most likely preceded caspase activation. Consistent with this conclusion was the observation that both apoptosis and loss of mitochondrial membrane potential (Δψm) were inhibited by cyclosporin A in combination with aristolochic acid. rhIL-6 protected cord blood mast cells from rhIL-4-induced apoptosis. Thus, IL-4 can cause both maturation and apoptosis of human mast cells, the latter effect being abrogated by IL-6.
Granulocyte-Colony Stimulating Factor Treatment of Lupus Autoimmune Disease in MRL-lpr/lpr Mice
Authors: Zavala Flora , Masson Annie , Hadaya Karine , Ezine Sophie , Schneider Elke , Babin Olivier , Bach Jean-François 
Published: December 2022

Abstract
G-CSF not only functions as an endogenous hemopoietic growth factor for neutrophils, but also displays pro-Th2 and antiinflammatory properties that could be of therapeutic benefit in autoimmune settings. We evaluated the effect of treatment with G-CSF in a murine model of spontaneous systemic lupus erythematosus, a disease in which G-CSF is already administered to patients to alleviate neutropenia, a common complication. Chronic treatment of lupus-prone MRL-lpr/lpr mice with low doses (10 μg/kg) of recombinant human G-CSF, despite the induction of a shift toward the Th2 phenotype of the autoimmune response, increased glomerular deposition of Igs and accelerated lupus disease. Conversely, high-dose (200 μg/kg) treatment with G-CSF induced substantial protection, prolonging survival by &gt;2 mo. In the animals treated with these high doses of G-CSF, neither the Th1/Th2 profile nor the serum levels of TNF-α and IL-10 were modified. Despite the presence of immune complexes in their kidney glomeruli, no inflammation ensued, and serum IL-12 and soluble TNF receptors remained at pre-disease levels. This uncoupling of immune complex deposition and kidney damage resulted from a local down-modulation of FcγRIII (CD16) expression within the glomeruli by G-CSF. Our results demonstrate a beneficial effect of high doses of G-CSF in the prevention of lupus nephritis that may hold promise for future clinical applications, provided caution is taken in dose adjustment.
B Cell Repertoire Diversity and Clonal Expansion in Multiple Sclerosis Brain Lesions
Authors: Baranzini Sergio E. , Jeong Matthew C. , Butunoi Catalin , Murray Ronald S. , Bernard Claude C. A. , Oksenberg Jorge R. 
Published: December 2022

AbstractMultiple sclerosis (MS) lesions in the CNS are characterized by disseminated demyelination with perivascular infiltrates of macrophages, T cells, and B cells. To investigate the origin and characteristics of the B cell population found in MS plaque tissue, we performed molecular studies in 10 MS patients and 4 non-MS control samples. Ig transcripts from the perivascular infiltrated brain lesions were analyzed by complementary-determining region 3 spectratyping to ascertain the B cell heavy chain gene rearrangement repertoire expressed in MS brains. Significant rearrangement diversity and deviation from the normal Ig heavy (H) chain repertoire was observed. The cloning and sequencing of RT-PCR products from families VH1 and VH4 showed a correlation with the profiles obtained by spectratyping. Generally, restricted spectratyping patterns concurred with repetition of in-frame complementary-determining region 3 identical sequences. The analysis of heavy chain variable (VH), diversity (D), and joining (JH) gene segments revealed the increased usage of VH1–69, VH4–34, and VH4–39. Similarly, gene segments from families D2, D3, and JH4 were over-represented. The presence of restricted patterns of rearranged Ig mRNA within the plaque lesion suggests that Ab production in the demyelinating plaque is a local phenomenon and supports the idea that in MS an Ag-driven immune response might be responsible for demyelination.
The Antigenic Substances of the Tubercle Bacillus
Authors: Dienes L. 
Published: December 2022

Summary
Date are given concerning the chemical composition of preparations of antigens 3, 4, 2 and 5. The preparations of antigens 3 and 4 contain large amounts of fatty substances. In the preparations of antigens 2 and 5 only 8 to 10 per cent are present. All preparations contain carbohydrates in varying amounts without apparent connection with the specific properties. The N content of the purified preparations of antigens 3 and 4 is low (0.3 to 0.4 per cent). In the preparations of antigens 2 and 6 which we analyzed it was somewhat higher (1.7 to 3.2 per cent).
From our observations it seems probable that in antigen 3 a specific part containing only little fat is in chemical connection with non-specific lipoid substances. We were not successful in determining the conditions under which the separation of the components occurs regularly. Studying the effect of water and HCl on the ether-solution of antigen 3 we made observations which probably will be of value for a more thorough study of this preparation.
Inflammation and Immunity
Authors: Opie Eugene L. 
Published: December 2022

Abstract
Existing knowledge of immunity is in large part concerned with the production of antibodies in experimental animals and the reactions of antibodies in vitro. Something is known about the way these agents act within the living body to neutralize or destroy invading microörganisms or other injurious substances but defects in our knowledge of the subject are very conspicuous. Many of the books on immunology include infection and immunity in their titles but there can be found in them little consecutive discussion of the fate of microörganisms after entering the body of an animal. Present knowledge of the subject is highly controversial and doubtless authors wisely refrain from discussions that would contain little more than speculation.
Inflammation may be defined as the process by which cells and serum accumulate about an injurious agent and tend to remove or destroy it (1). Phagocytes and other cells are mobilized at the site of invasion and plasma containing opsonins and the normal bactericidal substances of the blood exudes from the blood vessels.
Horse Serum as a Heterophilic Antigen. I
Authors: Davidsohn I. , Ramsdell Susan Griffith 
Published: December 2022

Summary
From the foregoing study there is evidence: Of the presence in horse serum of heterophilic antigens of the Forssman type, as shown by the development of a relatively strong antisheep hemolysin in rabbits immunized with large quantities of the serum. Absorption with heterophilic organs removed the hemolysin, while absorption with non-heterophilic organs diminished its titer only slightly, possibly due to physical absorption. The immune sera did not contain agglutinins for sheep red cells, neither did they contain hemolysins and agglutinins for horse and guinea pig red cells.That antistreptococcus serum has antigenic qualities similar to those of plain horse serum, while diphtheria globulin does not stimulate the production of heterophilic antibodies; and that subcutaneous injection of any one of the three sera fails to call forth a response.That the sera of rabbits, as a result of treatment, as outlined, become toxic for the guinea pig. This toxicity is shown to be not identical with the sheep cell hemolysin.
Antibody Studies in Serum Sickness
Authors: Tuft Louis , Ramsdell Susan Griffith 
Published: December 2022

Summary
In a study of the antibody response to immune sera as determined by serial bleedings of the patient, the Prausnitz-Küstner, the transferred guinea pig skin, and the passive anaphylactic reactions were shown to appear, usually, within three to ten days after treatment, and to have disappeared within thirty days—usually earlier. No one type of reaction occurred to a maximal extent in the absence of all the others in any given case; and no definite correlation could be established for the appearance of the various types. We were likewise unable to correlate the presence of any particular circulating antibody with the appearance of the phenomenon of serum sickness. Further, we have shown that serum sickness may occur (two instances) in the entire absence of circulating antibody of the types described.
Is the Sensitizing Effect of Cholesterol for the Antigen Used in the Complement-Fixation Test for Syphilis Due to the Contaminating Sterol, Ergosterol?
Authors: Maltaner Elizabeth 
Published: December 2022

Abstract
Cholesterol which is widely used to increase the sensitivity of antigens employed in the complement-fixation test for syphilis was for many years considered to be a chemically pure substance. Through the studies made recently, however, of cholesterol as a source of vitamin D, the antirachitic vitamin, it is now known that cholesterol, as ordinarily prepared, contains another sterol of an unsaturated and labile type of which ergosterol is the only known representative. Furthermore, it is because of this small amount of contaminating sterol that cholesterol, following irradiation with ultra-violet light, acquires antirachitic properties (1, 2, 3, 4). When ergosterol is removed, cholesterol is inert after irradiation (1, 2, 5, 6). Ergosterol, on the contrary, is very highly active.
In view of these observations, Professor Knudson of the Albany Medical College suggested that it would be of interest to determine whether cholesterol, after removal of the contaminating sterol, would lose its property of sensitizing the antigen used in the complement-fixation test for syphilis just as it loses its property of being rendered antirachitic by irradiation with ultraviolet light.
The Effect of Experimental Typhus Fever on B. Typhosus and Pneumococcus Agglutinins
Authors: Reimann Hobart A. , Wu C. J. 
Published: December 2022

Abstract
The Weil-Felix reaction or the presence of agglutinins for B. proteus X19 in the blood is of great value in the diagnosis of typhus fever. Except in clinical (1) and experimental (2) Rocky Mountain spotted fever this reaction rarely occurs during other febrile diseases (3) (4). On the other hand, the presence or appearance of the Widal reaction, or agglutinins for typhoid bacilli in the serum is a common occurrence during typhus fever. During typhus, the Widal reaction may appear alone or together with the Weil-Felix reaction and is often stronger and increases in titer more rapidly than the Weil-Felix reaction, thus often giving rise to confusion in making early diagnoses. The temperature curve of a case of undoubted typhus fever in which both reactions were encountered is illustrated in figure 1. This patient had been immunized with typhoid and paratyphoid A and B vaccine one year prior to his illness.
Diagnosis of Glanders by Precipitation with So-Called “Soluble Specific Substance” Derived from B. Mallei
Authors: Sakamoto K. 
Published: December 2022

Summary
Two substances could be isolated from culture filtrate of B. mallei, of which one seems to be the nucleoprotein in nature and the other the specific substance analogous to that of pneumococcus, streptococcus etc. Preliminary chemical examination indicates that this specific substance may belong to carbohydrates. The former—the so-called N.P.—is relatively nonspecific and gives rise to nonspecific precipitation. The relative nonspecificity of the precipitation reaction with the culture filtrate (or mallein) seems to depend upon this substance. The latter substance is highly specific; it gives rise to precipitation only with sera of infected or artificially immunized animals, but not with those of animals neither infected nor immunized with B. mallei. Specific precipitation with this specific substance is closely related to the complement-fixation reaction. The precipitation test with this specific substance appears the most simple and reliable means for the practical diagnosis of glanders applicable as well to mules and donkeys, as to horses.
Use of Broth Culture Filtrates in Anaphylaxis Experiments
Authors: Sugg John Y. , Neill James M. 
Published: December 2022

Summary
Experiments were made on two questions. First, the primarily toxic (anaphylactoid) action was studied by intravenous injection of normal guinea pigs with formolized and unformolized filtrates of diphtheria and other bacilli and with the non-bacterial constituents of the filtrates (uninoculated broth, solutions of phenol and of formol). The possibility of sensitization to the non-bacterial constituents during immunization with the filtrates was studied by intravenous tests on animals previously given repeated subcutaneous injections of formol solution or of formolized broth. With diphtheria filtrates, neither the primary toxicity nor the possibility of sensitization to the broth constituents, introduced significant complications in their use as material for active sensitization and for subsequent intravenous tests. The adaptability of broth culture filtrates of other bacteria to anaphylaxis experiments would depend upon the quantitative effectiveness of the antigens they liberate into their culture fluids.
On the Heatstability of the Scarlet Fever and Diphtheria Toxins
Authors: Ando K. 
Published: December 2022

Abstract
The thermostability of scarlet fever toxin has been dealt with by many authors and this property is one of the reasons that aroused suspicion as to the exotoxic nature of this toxin and also as to the toxin-antitoxin theory of the Dicks. There are many reports that even boiled Dick toxin (scarlet fever streptococcus culture filtrate) is capable of eliciting skin reactions in human beings if it is used in a dose corresponding to 1 or more skin test doses. But it must be noted that positive reactions to a dose of boiled toxin corresponding to 1 s.t.d. seem to have been found mainly by those authors who employed a streptococcus filtrate toxin containing blood element.
The Preparation of Antigens from Cultures of Treponema Pallidum
Authors: Wadsworth Augustus B. , Van Amstel Jeanne E. , Brigham Margaret W. 
Published: December 2022

Summary
The conclusions of this work are based upon the study of one strain of the Treponema pallidum.
The results with aqueous and alcoholic extracts of Treponema pallidum agree essentially with the original observations of Noguchi. By the aqueous extraction of the organisms antigenic substances were obtained which react in a marked degree with sera from rabbits immunized with the same cultural strains, but not with syphilitic rabbit or syphilitic human sera. Under the conditions of our experiments either the antigenic substances which react with rabbit immune sera, syphilitic rabbit, and syphilitic human sera were not readily extractable in ethyl alcohol or were present in very low concentration. The addition of cholesterol to the aqueous, strong salt and alcoholic extracts of Treponema pallidum did not increase their sensitivity but in the case of the alcoholic extracts especially, it rendered them extremely anticomplementary. The results obtained with dialyzed aqueous extracts of Treponema pallidum which had been previously extracted with alcohol indicate that the antigenic substances obtained by aqueous extraction of the organism differ from those obtained by extraction with alcohol. Antigenic substances which reacted with rabbit immune sera, with syphilitic rabbit, and markedly with syphilitic human sera, were obtained by the extractions of uninoculated medium with alcohol. Slightly increased antigenic activity was noted with similar extracts of the whole culture medium containing Treponema pallidum. These observations suggest that the divergent results which are reported in the literature concerning the solubility in alcohol of antigenic substances of this organism may be due to differences in the media used and the culture materials which were extracted. Treponema pallidum produced in culture substances which fixed complement in the presence of very small amounts of the sera of rabbits immunized with the homologous strain and the activity of these substances corresponded to that obtained by aqueous extracts of the treponemata free from medium.