bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement and Feline Leukemia
Authors: O'Neill G. J. , Hardy W. D. , Kassel R. , Old L. J. , Day N. K. 
Published: January 2023

Abstract
Our interest in complement and leukemia has emerged from studies by Kassel et al. (J. Exp. Med., 138:925, 1973) and Hardy et al. (unpublished results) that infusion of normal plasma in mice, cats, and dogs causes massive dstruction of leukemic cells. Evidence in the mouse indicates that the anti-leukemic factor is a component of the complement system, C5. We have therefore begun to assay C and C component levels in cat serum. With functionally pure C1 and C2 and intermediate cells (EAC1, EAC4, EAC1,4) prepared from cat serum, the measurement of C1, C4 and C2 can be accomplished when the source of terminal C components, C3 to C9 is guinea pig serum in EDTA. With cat serum in EDTA, lysis does not occur. The blocking effect appears to be due to a potent inhibitor present in cat serum. This inhibitor is anti-complementary to guinea pig and human serum.
Complement Dependent Adherence, Phagocytosis and Hemolysis Initiated by C-Reactive Protein (CRP)
Authors: Osmand A. P. , Mortensen R. F. , Gewurz H. 
Published: January 2023

Abstract
Interactions of CRP with several substances have been shown to result in activation of the C system at the level of C1. By using sensitized C-polysaccharide-coated erythrocytes (E-CPS), we have investigated both the qualitative and quantitative differences between IgG antibody and CRP in their ability to promote a variety of C-dependent reactions. Sensitization with CRP or antibody to CPS (1 to 10 µg/ml) rendered E-CPS susceptible to C-dependent lysis during incubation with suitably absorbed human or guinea pig sera. Extensive hemolysis (60 to 85%) in C4- and C2-deficient sera and potentiation by human C1q of hemolysis by guinea pig serum were suggestive both of the ability of CRP and antibody to activate the C1-bypass and of the sensitivity of the cells to this C pathway. The ability of CxRP, the analogous protein in the rabbit, to promote these reactions indicated that these properties are a general function of C-reactive proteins.
C1q Binding Substances in Cancer and Complement Deficient Sera
Authors: Teshima H. , Kunkel H. G. , Day K. Noorbibi 
Published: January 2023

Abstract
We recently reported the presence of C1q-binding substances in serum of a patient with CLL and circulating antigen-antibody complexes (Day et al., Clin. Res. 23:410a, 1975). We have extended this observation to study of patients' sera with various forms of malignancies and with genetically inherited C deficiencies (c1r, C2, and C3). Two methods are used: one by a modified agar diffusion (Agnello et al., Immunology 19:909, 1970) and two, by the C1q deviation test (Bokisch et al., Clin. Res. 23:409a, 1975). The modified agar diffusion test correlated with C1q levels determined by the Mancini technique (normal: 17 to 23.5 µg/ml). Fifteen of 50 malignant sera (2/3 breast, 2/2 melanoma, 5/12 acute myelogenous leukemia, 1/1 chronic lymphatic leukemia, 1/1 oat cell, 2/3 esophagus, 1/5 rectal, 1/5 ovary, 1/1 bone) wath low levels of C1q (&lt;10 µg/ml) were strongly positive by the precipitation test. These low sera also showed high C1q-binding activity in the C1q deviation test.
Activation of the C1r Subunit of C1 by Proteolytic Cleavage
Authors: Ziccardi R. J. , Cooper N. R. 
Published: January 2023

Abstract
C1r, isolated by an improved method, was found to be a 190,000-dalton glycoprotein consisting of two non-covalently linked 95,000 dalton polypeptide chains. Antisera to C1r detected a protein with a sedimentation coefficient of 19S on ultracentrifugation of serum in the presence of calcium and a 7S protein on analysis in EDTA. No reaction with C1r-deficient sera was observed. Isolated C1r formed C1 in the presence of C1q and C1s. Binding of 125I-C1r to sensitized sheep erythrocytes required the presence of C1q and calcium but not C1s, whereas the binding of 125I-C1s required C1q and C1r and calcium. Thus C1r serves as the physical link between C1q and C1s is macromolecular C1.
Acquisition of ability to activate C1s was associated with cleavage of each of the noncavalently bonded 95,000 dalton chains into disulfide linked subunits of 60,000 and 35,000 daltons, respectively. Thus, C1r is converted from a precursor form by proteolytic cleavage into an enzyme, C, able to cleave and activate C1s.
Opinion
Authors: Kilbourne Edwin D. 
Published: January 2023

Abstract
Influenza persists in this last quarter of the 20th century as an important cause of wholesale human incapacity and death. Paradoxically, it does so in the face of recent improvements in inactivated vaccines developed 30 years ago and striking advances in the understanding of the structure, replication, and genetics of the influenza viruses during the past decade. Neither prior infection nor artificial immunization provides lasting immunity against the constantly changing virus of influenza. In part, the transient protection induced by presently available inactivated viral vaccines is related to rapid decline of vaccine-induced homologous antibody; in part, vaccine obsolescence is the result of viral mutation to antigens unlike or less like those contained in the vaccine.
The threat of pandemic influenza is so awesome that major efforts are required for its curtailment upon even the hint of its inception, as was the case with swine influenza during 1976 (1).
Nonspecific Activation of Murine Lymphocytes
Authors: Goodman Michael G. , Weigle William O. 
Published: January 2023

Abstract
Recent evidence has indicated that addition of 2-mercaptoethanol (2-ME) to culture medium is able to activate murine lymphocytes to undergo blastogenesis, to synthesize polyclonal antibody, and to develop cytotoxicity to both autologous and heterologous target cells. In order to explore the basis for these phenomena, a study of the physical interaction between the cell and 2-ME was undertaken by using a radiolabeled preparation of 2-ME. Uptake of labeled 2-ME increased over the initial 24 hr of culture, after which a steady state was achieved. Cells were found to have maximal susceptibility to activation by 2-ME after incubation for 24 hr in the absence of the thiol compound. This observation was not explicable in terms of any alteration in the kinetics of 2-ME uptake. The amount of labeled 2-ME taken up was a function of the 2-ME concentration with which the cell was incubated, with the exception of the concentration range that is optimal for mitogenesis. At this range, the curve was suggestive of a saturation effect. Uptake by B cell cultures was found to exceed that by T cell cultures. Uptake was shown to result from interaction with protein, to be independent of metabolic energy, to be governed by temperature-dependent kinetics, and to be highly specific.
Genetic Control of Immunologic Unresponsiveness to Adjuvant-Free Solutions of β-D-Galactosidase
Authors: Rotman Boris 
Published: January 2023

Abstract
Two genetic loci, Ir-Z1 and ir-Z2, controlling the immune response to adjuvant-free bacterial β-D-galactosidase (Z) are present in inbred mouse strains SJL/J and CE/J, respectively. Each locus segregates as a single, autosomal gene: Ir-Z1 as dominant and ir-Z2 as recessive. The response is characterized by production of activating and precipitating IgG. Maximal levels of circulating IgG occur between 16 and 20 days after immunization with a single, 50-µg dose of enzyme. Failure of proteins other than Z to elicit an immune response indicates that the Ir-Z control is specific for determinant(s) of this enzyme. The immunogenicity of β-D-galactosidase preparations cannot be attributed to either the catalytic activity of the enzyme or adjuvant contamination. Non-responder mice acquire immunologic memory without detectable increase in circulating specific IgG under the same conditions that elicit antibody production in responder strains.
Patterns of Expression of Human “Ia-Like” Antigens during the Terminal Stages of B Cell Development
Authors: Halper J. , Fu S. M. , Wang C. Y. , Winchester R. , Kunkel H. G. 
Published: January 2023

Abstract
The “Ia-like” antigens characteristically present on the membrane of B lymphocytes were shown to be absent in most terminally differentiated Ig-producing plasma cells. This was most evident in analyses of myeloma plasma cells that uniformly lacked the Ia-antigens. Also, in B lymphoid cell lines, the lymphoblasts were uniformly Ia-positive but the plasma cells were negative. In contrast, however, the majority of plasma cells produced after pokeweed mitogen stimulation remained positive. Plasma cells in tonsil and in the tissue of peripheral blood of patients with Waldenström's macroglobulinemia were also sometimes Ia-positive although the majority were negative. Studies of membrane IgM and IgD indicated a similar loss in some instances. However, the SIg and Ia antigens were not invariably associated. These results lead to the conclusion that Ia-antigens are differentiation antigens for B cells and are usually lost by the end stage cells in this series.
Characterization of Lymphocyte-Activating Factor (LAF) Produced by a Macrophage Cell Line, P388D1
Authors: Mizel Steven B. , Oppenheim Joost J. , Rosenstreich David L. 
Published: January 2023

Abstract
Unstimulated P388D1 cells, as well as P388D1 cells stimulated with PHA-activated guinea pig T lymphocytes or LPS, produced a lymphocyte activating factor (LAF). In order to have a chemical basis for comparing this LAF with the LAF produced by normal macrophages, we have analyzed several biochemical characteristics of the P388D1-derived LAF. Sephadex G-75 chromatography of concentrated LAF-containing supernatants from cultures of unstimulated and T cell stimulated P388D1 cells demonstrated that the cell line LAF had a m.w. of approximately 16,000. On DEAE cellulose, the T cell-induced LAF fractionated into at least three major peaks and one minor peak. By using hydroxylapatite chromatography, two of the major peaks of LAF activity were separated from residual contaminating Lowry positive material.
LPS-stimulated P388D1 also produced LAF with a m.w. of 16,000. However, the LPS-induced LAF appeared to lack one of the DEAE peaks of LAF activity observed with the T cell-derived LAF. In contrast to LPS, T cells may induce the synthesis and/or release of an additional LAF component or enzymatically modify one or more of the LAF species that are produced in response to both stimulants.
Based on the results of chemical characterization studies, the P388D1-derived LAF appears to be similar in size and charge to the lymphocyte activating factor produced by normal macrophages.
The Activation of Lymphocytes by the Ionophore A 23 187
Authors: Resch Klaus , Bouillon Dorothea , Gemsa Diethard 
Published: January 2023

Abstract
The possible mechanism by which a divalent cation ionophore, A 23 187, initiated the activation of lymphocytes was investigated. Rabbit lymphocytes were cultured in the presence of the ionophore, the T cell mitogen Con A, or the B cell mitogen GARIG serum. The proliferative response, assessed by incorporation of 3H-thymidine into DNS, as well as the increase in incorporation of 3H-uridine induced by the ionophore was comparable to that caused by the receptor-binding B mitogen in T-B mixtures. Thymocytes responded weakly and inconsistently to the ionophore, whereas purified B lymphocytes proved to be highly reactive, suggesting that A 23 187 is primarily a B mitogen in rabbits. Removal of macrophages did not impair the activating capacity of the ionophore. To initiate cell activation the ionophore had to be present for at least some hours.
At optimal concentrations of Ca++ (1 mM), increasing doses of Mg++, which has the same binding affinity to the ionophore but does not support activation, did not suppress the response to the ionophore. Similarly, Mn++ which binds to the ionophore with a 100-fold higher affinity than Ca++ was not able to interfere with the activation of lymphocytes. Both ions, however, inhibited the ionophore-dependent Ca++ influx at concentrations not affecting activation. Within 1 hr of contact the ionophore increased the turnover of the phospholipid fatty acids. The dose response curve for the activation of the membrane phospholipid metabolism and that for the stimulation of RNA or DNA synthesis were identical.
These data suggest that the ionophore A 23 187 interacts directly with rabbit (B) lymphocytes to induce cell activation. The activating capacity does not depend on the translocation of Ca++. We propose that the ionophore intercalates into the lipid phase of the plasma membrane, initiating the same changes in the membrane itself that are induced by mitogens that bind to surface receptors, i.e., increasing the turnover of membrane phospholipids.
Progressive Changes in Cytotoxic Potential during Mixed Lymphocyte Culture
Authors: Touton Mary H. , Clark William R. 
Published: January 2023

Abstract
In a previous study it was shown that at least one round of DNA synthesis is required for initial expression of cytotoxic function in mouse lymphocytes responding to alloantigen in vitro. In the experiments reported here we ask whether subsequent rounds of cell division are required simply for clonal expansion of this initial level of cytotoxic function within the population, or whether the amount of cytotoxicity per cytotoxic cell is altered during subsequent rounds of cell division. The amount of cytotoxicity per unit number of cells at various stages of culture was compared with the frequency of cytotoxic cells as estimated principally by effector-target cell conjugates. Our results strongly suggest that the amount of cytotoxicity per cell (cytotoxic potential) is not a static property of cytotoxic cells, but can be modulated up or down during the course of a reaction.
Melanoma-Associated Immunosuppression through B Cell Activation of Suppressor T Cells
Authors: Ninnemann John L. 
Published: January 2023

Abstract
Using normal human lymphocytes isolated by sedimentation and cotton column adherence, we have developed a reliable assay of immunosuppression of PHA-induced blastogenesis by serum from selected melanoma patients. These lymphocyte cultures contained both responder cells (subpopulation x) and regulator cells (subpopulation y). Lymphocytes isolated by gradient centrifugation on sodium metrizoate-Ficoll contained responder cells (x) but no regulator cells (y). Cultures of lymphocytes isolated by this method were stimulated by PHA but were not suppressed by the addition of melanoma serum. When lymphocytes were isolated by a cotton column adherence/Lymphoprep centrifugation-double separation, subpopulations (x) and (y) were isolated. We have established that both subpopulations are necessary for suppression to occur, and that (y) operates as the regulator of (x). Finally, by manipulating B cell and T cell populations isolated by nylon column adherence or AET rosette separation, we have determined that the regulator ability of subpopulation (y) is the result of B cell activation of suppressor T cells.
Trypan Blue Inhibits Complement-Mediated Phagocytosis by Human Polymorphonuclear Leukocytes
Authors: Guckian James C. , Christensen Wayne D. , Fine Douglas P. 
Published: January 2023

Abstract
Trypan blue completely inhibited attachment of human polymorphonuclear leukocytes (PMN) to Sepharose beads coated with C3 and to sheep erythrocytes coated with IgM plus C3, but it did not inhibit attachment to erythrocytes coated with IgG. These results suggested that trypan blue inhibited C-mediated attachment to PMN membranes. Corroborative studies were performed with a strain of Staphylococcus aureus that requires C but not antibody, for opsonization and that activates the alternative pathway. Trypan blue was not toxic to PMN or bacteria, did not interfere with immunoglobulin or C interactions, and did not affect attachment of opsonins to bacteria. However, the dye impaired PMN killing of S. aureus in normal nonimmune serum by inhibiting bacterial attachment to and ingestion by PMN. Further evidence that the inhibition was at the C3 receptor level came from the observations that, 1) once staphylococci were attached to PMN at either 37°C or 0°C, addition of trypan blue did not inhibit killing; and 2) trypan blue inhibited killing of bacteria opsonized with serum sufficient in C but previously absorbed at 0°C with the same strain of organism to deplete specific antibody. Further studies with this agent may elucidate the roles of opsonic receptors on human phagocytes.
Mechanisms of Regulation of Cell-Mediated Immune Responses
Authors: Greene Mark I. , Sugimoto Masanobu , Benacerraf Baruj 
Published: January 2023

Abstract
A new method for inducing contact sensitivity (CS) responses has been developed. The subcutaneous injection of trinitrophenyl (Tnp)-derivatized syngeneic spleen cells into BALB/c mice, without adjuvant, could lead to significant ear swelling CS responses upon challenge of the ear with the same hapten, i.e., picryl chloride (PCI). This response was transferred by lymphoid cells obtained from immunized animals. Such cells were judged to be thymus-derived (T) cells as they could be obtained by nylon wool passage and were sensitive to treatment with AKR anti-Thy 1.2 serum and C. The response displayed the characteristic time course of cell-mediated immune reactions and was maximal at 24 hr after challenge. Histologic investigation revealed a marked mononuclear cell infiltration into the lesion site.
The i.v. administration of either 2,4,6-trinitrobenzene-sulfonic acid (TNBS), or the same moieties capable of eliciting CS, viz, Tnp cells or Tnp cell membranes, could suppress the generation of Tnp cell-induced CS reactions. It was also possible to suppress the CS response by the i.v. transfer of suppressor T cells or factor(s) obtained from suppressed mice.
Furthermore, it was found that Tnp-derivatized syngeneic macrophage (Mø) were more capable of inducing CS responses than similarly derivatized spleen cells or thymocytes, suggesting that Mø surface was a better presentation template for the induction of CS. The notion that the route of presentation of hapten-modified syngeneic membranes dictates the response evoked, i.e., immunity when presented subcutaneously but suppression when the encounter is via the i.v. route, is discussed.
Role of Interferon in the Pathogenesis of Viral Diseases of Mice As Demonstrated by the Use of Anti-Interferon Serum
Authors: Virelizier Jean-Louis , Gresser Ion 
Published: January 2023

Abstract
Potent sheep anti-mouse interferon globulin has been used to determine the role of virus-induced interferon in mouse hepatitis virus type 3-infected susceptible (C57BL/6), semiresistant (C3H/He), and resistant (A/J) strains of mice. Injection of anti-interferon globulin accelerated the onset of death in C57BL/6 mice, induced almost 100% mortality in C3H/He mice that usually do not die of acute disease, and caused death in 4- and 6-week-old A/J mice, but not in older mice. We conclude that interferon is an important host defense factor in the initial response of different strains of mice to MHV-3 infection. Other factors, however, such as the capacity of macrophages to restrict viral multiplication probably underlie the genetically determined susceptibility or resistance of mice to MHV-3 infection.
Inhibition of the Alternative Pathway of Complement by Gold Sodium Thiomalate in Vitro
Authors: Burge Joseph J. , Fearon Douglas T. , Austen K. Frank 
Published: January 2023

Abstract
Gold sodium thiomalate (AuTM) in molar concentrations comparable to those observed in plasma of patients undergoing treatment of rheumatoid arthritis inhibits the interaction of C3b, B, and D̄ to form the amplification C3 convertase (C3b,Bb). The inhibitory action of AuTM is dose related and occurs whether or not P is present to stabilize the C3b,Bb convertase. When the convertase is formed in the absence of D̄ so as to be C3b,B, a higher concentration of AuTM is required for inhibition, suggesting an action not only to prevent the association of B with C3b but also on the presentation of the bimolecular complex as a substrate for D̄. Thiomalate alone was not inhibitory and AuTM had no irreversible effects on cell-bound C3b or fluid phase B, D̄, or P. AuTM did not enhance the decay or inhibit the active site of the preformed C3 convertase generated with cleaved or uncleaved B, with or without P stabilization. AuTM is most active in inhibiting convertase formation on cellular intermediates bearing the lowest number of 125I-C3b per cell and requiring development with the highest B concentration, suggesting the binding site on C3b for B as the locus of AuTM action. This interpretation is compatible with the ability of AuTM to prevent B proteolysis during the fluid phase interaction of C3b, B, and D̄. AuTM is a reversible inhibitor of the formation of C3b,Bb, the amplification C3 convertase of the complement system and thus modulates a critical step in the entire reaction sequence.
Murine Ia Antigens: Identification and Mapping of Ia.23 and Further Definition of the I-E Subregion
Authors: David Chella S. , Cullen Susan E. 
Published: January 2023

Abstract
The Ia.23 specificity is a private specificity of the H-2d haplotype which we have assigned to the I-E subregion. It is found on the same Ia molecule that bears Ia.7, a public specificity previously assigned to the I-C subregion of haplotypes H-2d, H-2k, H-2p and H-2r. We suggest a reassignment of specificity Ia.7 to the I-E subregion to simplify the interpretation of the data presented in this paper and elsewhere, and to permit an orderly description of that part of the I region to the right of I-J.
Inhibition of the Induction of Cytolytic T Lymphocytes with Alloantisera Directed against H-2K and H-2D Gene Products
Authors: Lemonnier Francois , Burakoff Steven J. , Mescher Matthew , Dorf Martin E. , Benacerraf Baruj 
Published: January 2023

Abstract
Alloantisera directed at gene products of the H-2Kd or H-2Dd loci on the stimulator cell were shown to inhibit specifically the generation of cytolytic T lymphocytes to those antigens. Thus, masking the antigens of one H-2 locus on the stimulator cell inhibits the induction of CTL to products of that locus but does not inhibit the induction of CTL to antigens of another H-2 locus. Alloantisera inhibition of the induction of cytolytic T lymphocytes occurred with both normal and primed responder cells and also occurred when the stimulating antigens were on whole cells or purified plasma membrane. Absorption on the appropriate spleen cells removed the inhibitory capacity of these alloantisera.