bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Physicochemical and Immunologic Comparison of the Cell Growth Inhibitory Activity of Human Lymphotoxins and Interferons in vitro
Authors: Ware Carl F. , Granger Gale A. 
Published: December 2022

Abstract
The physicochemical, immunologic, and biologic relationships between human lymphotoxins (LT) and interferons (IF) present in supernatant fluids from lectin-stimulated peripheral blood lymphocytes (PBL) and a continuous B-lymphoblastoid cell line (PGLC-33h) were analyzed. LT activity obtained from lectin-activated PBL could not be resolved from IF activity by gel filtration chromatography. LT activity eluted in multiple peaks of activity at 70 to 90,000, and 40 to 50,000 m.w., characteristic of α and β LT, respectively. IF activity in these supernatant fluids eluted as a broad band between 35 and 80,000 m.w., also suggestive of molecular heterogeneity. In contrast, this m.w. heterogeneity was not observed in LT and IF activities obtained from the PGLC-33h cell line. LT and IF eluted as separate peaks of activity at 90,000 and 25,000 m.w., respectively. In addition, acid and heat lability of PGLC-33h IF suggested similarity to type II IF. Immunologic studies, with a rabbit anti-α class serum that neutralized LT activity from both PBL and PGLC-33h, did not affect IF activity from either of these sources.
Supernatant fluids from PGLC-33h cultures were also capable of inhibiting the proliferation of HeLa cells in vitro. The growth inhibitory activity was attributed to LT- and IF-like molecules. This evidence suggests that although cytotoxic and anti-viral activities were due to separate molecules, LT and IF have overlapping biologic activities in their ability to inhibit the proliferation of cells in vitro.
DRw Antisera React with Activated T Cells
Authors: DeWolf William C. , Schlossman Stuart F. , Yunis Edmond J. 
Published: December 2022

Abstract
Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with “Ia-like” antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear.
Human B Cell Differentiation
Authors: Bich-Thuy Le Thi , Brochier Jean 
Published: December 2022

Abstract
In vitro human plasma cell generation induced by both T-dependent (PWM) and T-independent (NWSM) mitogens was found to be suppressed by peripheral blood lymphocytes preincubated with human aggregated IgG. T cells, but not B lymphocytes, were able to mediate the suppressive activity; since aggregated (Fab)′2 fragments were found unable to generate suppressor cells, it was concluded that the suppressor cell was a T lymphocyte bearing Fcγ receptors. These cells appeared to be largely radiosensitive. In most cases the proliferative responses remained unchanged. Since NWSM-induced activation is not dependent on the presence of T cells, these results show that, at least in this case, T cells exert their suppressor function directly on B lymphocytes. Whether PWM-induced B cell differentiation is suppressed by the same mechanism or/and by inactivation of T helper lymphocytes remains under investigation.
Somatic Cell Hybrids of Mouse Myeloma Cells and B Lymphocytes from a Patient with Agammaglobulinemia: Failure to Secrete Human Immunoglobulin
Authors: Schwaber Jerrold F. , Rosen Fred S. 
Published: December 2022

Abstract
Somatic cell hybrid clones were isolated from the fusion of RPC5.4 mouse myeloma cells and B lymphocytes from a patient with common varied agammaglobuinemia. The patient has B lymphocytes that synthesize immunoglobulin but fail to secrete immunoglobulin. The hybrid character of the six clones was established by examination of metaphase chromosome spreads. Most of the hybrid clones expressed mouse and human surface immunoglobulin. All of the clones synthesized immunoglobulin of mouse and human parental origin. Mouse parental immunoglobulin was secreted, whereas the human parental immunoglobulin was not secreted. Human light chain molecules were secreted as part of hybrid H2L2 molecules formed with mouse heavy chains. Human heavy chains had a reduced m.w. in comparison to the mouse heavy chains. Kinetic experiments indicated that human Ig was synthesized in amounts that were comparable to the mouse Ig. Pulse-chase experiments showed that that the intracellular human Ig was removed from the cytoplasm, probably by degradation. These experiments demonstrate that the hybrid cells are an in vitro model of naturally occurring failure of immunoglobulin secretion from agammaglobulinemia. The failure of fusion with mouse myeloma cells to complement the secretion defect suggests that these B cells produce an altered immunoglobulin molecule that is not programmed for secretion.
Mechanisms of Leukemogenesis
Authors: Schenk Paul J. , Howe Michael L. 
Published: December 2022

Abstract
Examined in this paper is the capacity of 334C murine leukemia virus (MuLV) to stimulate the generation of virus-specific cytotoxic effector cells in mice of the C57BL/6 strain that are relatively resistant to Friend, Moloney, and Rauscher (FMR) MuLV-induced leukemia, and in BALB/c mice that are relatively susceptible to leukemia induced by FMR MuLV. Generation of cytotoxicity requires in vivo administration of the virus followed by in vitro culture of lymphoid cells from virus-injected animals. Lymphoid cells from MuLV-resistant C57BL/6 donors develop high levels of specific cytotoxicity after secondary in vitro stimulation with syngeneic MuLV-induced tumor cells. Cells derived from these same donors, cultured in the absence of MuLV-induced tumor cells, fail to exhibit cytotoxicity. Secondary in vitro stimulation of lymphocytes from MuLV-susceptible BALB/c animals results not only in generation of cytotoxic reactivity against syngeneic MuLV-induced tumor cells but also induces apparently autoreactive effector cells capable of lysing other H-2d tumor cells as well as normal peritoneal cells bearing H-2d antigens. Moreover, generation of cytotoxicity by BALB/c lymphocytes occurs whether or not MuLV-induced tumor cells are included in the secondary culture system.
Immune Suppression in vivo with Antigen-Modified Syngeneic Cells
Authors: Sherr David H. , Cheung Nai-Kong V. , Heghinian Krikor M. , Benacerraf Baruj , Dorf Martin E. 
Published: December 2022

Abstract
Intravenous administration of syngeneic spleen cells coupled with the palmitoyl derivative of fowl γ-globulin (p-FγG) results in a profound state of FγG-specific tolerance in C57BL/6 mice. Administration of p-FγG coupled syngeneic cells specifically reduces both the primary and secondary hapten and carrier-specific PFC responses to TNP-FγG. Since the haptenic response is affected, the tolerance functions at the level of the FγG-specific helper T cell. As few as 103 p-FγG spleen cells carrying only 1 ng of p-FγG can induce tolerance. At least a 2-day-induction period is required. This nonresponsiveness is long lived, lasting over 120 days. Spleen cells from tolerized mice can transfer suppression to normal syngeneic recipients. Treatment of tolerant spleens with anti-Thy 1.2 antiserum + C eliminates the suppressor cell activity. In addition, thymocytes and purified splenic T cells from tolerized mice can transfer suppression to normal recipients. Thus, at least a component of this nonresponsiveness is mediated by suppressor T cells. The requirement of antigen association with cell membrane components and the general applicability of this method of inducing T cell nonresponsiveness are discussed.
The Structural Basis of a Hapten-Inhibitable κ-Chain Idiotype
Authors: Vrana Mark , Rudikoff Stuart , Potter Michael 
Published: December 2022

Abstract
The complete κ-chain variable region sequences from two murine myeloma proteins (U-61 and E-109) with binding specificity for β(2-1) fructofuranosyl moieties have been determined. The two κ-chains differ from each other by four amino acids. Earlier studies with recombinant molecules have assigned three different idiotypes to these two light chains. One of these determinants is hapten inhibitable and is presumed to be in or near the combining site, whereas the remaining two are not hapten inhibitable. Analysis of the four sequence differences found between these two chains in conjunction with a hypothetical three-dimensional model of the anti-fructan antibodies reveals that the hapten-inhibitable idiotype appears to be determined by the association of two amino acids found in complementarity-determining regions I and III. One of the nonhapten-inhibitable determinants could be caused by any of the three substitutions occurring in the framework portion of the variable region. The second of these determinants appears to result from the three-dimensional proximity of more than one framework amino acid.
A comparison of the U-61 and E-109 structures with partial sequences from several other light chains from fructofuranose-binding proteins revealed a total of eight differences occurring both in framework and complementarity-determining regions. The identification of Ser in two proteins at residue 30 and Asn at this position in three other proteins suggests that despite the great degree of homology exhibited by these light chains at least two germline genes would be required to code for these molecules.
Is Genetically Related Macrophage Factor (GRF) a Soluble Immune Response (Ir) Gene Product?
Authors: Erb Peter , Meier Barbara , Feldmann Marc 
Published: December 2022

Abstract
The possibility that the antigen-presenting “macrophages” interacting with helper cells either directly or via the intermediary action of a soluble factor consisting of Ia antigen and a fragment of immunogen, termed GRF (genetically related factor), are a site of Ir gene action was investigated by using the synthetic polypeptide antigen (T,G)-A—L. It was found that T cells from (responder × nonresponder) F1 mice were stimulated by responder “macrophages” or GRF derived from these cells but not by the nonresponder macrophages of GRF from these cells. This suggests that the defect in helper cell induction in nonresponders is at the level of the presenting cell and that the macrophage factor GRF is a soluble Ir gene product. This conclusion was supported by the observation that there was normal presenting cell and GRF function in nonresponders, mouse strains such as CBA that yield helper cells and helper factor with (T,G)-A—L and have defects elsewhere.
Two Migration Inhibitory Factors Differ in Density and Susceptibility to Neuraminidase and Proteinases
Authors: Remold Heinz G. , Mednis Alma D. 
Published: December 2022

Abstract
It has been shown that migration inhibitory factor (MIF) from guinea pigs can be separated into two subfractions. These are pH3-MIF (isoelectric point of 3.0 to 4.5 and apparent m.w. of 65,000) and pH5-MIF (isoelectric point of 5.0 to 5.5 and apparent m.w. of 25,000 to 40,000). Upon centrifugation of pH3-MIF in CsCl gradients, activity was found in the density range of 1.38 to 1.46 g/ml. pH5-MIF banded in CsCl gradients in fractions with a density ranging from 1.29 to 1.38 g/ml. Thus, pH3-MIF bands with glycoproteins having a high carbohydrate content. pH5-MIF has a density similar to pure proteins or to glycoprotein with low carbohydrate content. This interpretation is reinforced by the finding that pH3-MIF is neuraminidase sensitive, whereas pH5-MIF is neuraminidase resistant. Furthermore, the activity of pH5-MIF but not that of pH3-MIF was destroyed by treatment with trypsin. In contrast, chymotrypsin inactivated both MIF species. Thrombin and plasmin, on the other hand, did not inactivate pH5-MIF or pH3-MIF. The activity of pH5-MIF was also destroyed by incubation with peritoneal exudate cells, whereas the activity of pH3-MIF was unaltered after incubation with peritoneal exudate cells. Reaction of the peritoneal exudate cells with diisopropylfluorophosphate abolished their ability to inactivate pH5-MIF. Thus, inactivation of MIF is caused by a cell-associated serine protease(s) that may play a role in the regulation of the macrophage's response to one MIF species.
Studies of Congenitally Immunologic Mutant New Zealand Mice
Authors: Gershwin M. Eric , Castles James J. , Erickson Kent , Ahmed Aftab 
Published: December 2022

Abstract
Congenitally athymic (nude) mice on an NZB, NZW, and BALB/c background were produced by repetitive selective backcrossing. F'12 generation nude mice of these three strains were compared to their littermate nu/+ controls with respect to survival, histology, blood counts, splenic surface markers, response to mitogens, spontaneous plaque-forming cells, and appearance of naturally occurring thymocytotoxic antibodies (NTA). Under specific pathogen-free conditions, NZB nude mice survive less than 3 weeks, dying of a runting-like disease with infection by local normally noninvasive organisms. A contributing factor to this premature death is the relative absence of T cell progenitor populations in the NZB nude vs NZW nude or BALB/c nude groups. Furthermore, NZB nude mice have a significantly earlier appearance of NTA than nu/+ littermates and likewise appear to have heightened spontaneous polyclonal B cell responses against the haptens dansyl, nitroiodophenyl, trinitrophenyl, 2,4 dinitrophenyl, and sulfonate. It is suggested that NZB mice have several critical immunologic defects, including abnormalities of thymic epithelial cells, T cell differentiation pathways, and chronically polyclonal activated B cell populations. These defects interact to produce the clinical expression of autoimmunity.
Determination of the Number of Lytic Sites in Biconcave and Spheroid Erythrocyte Ghosts After Complement Lysis
Authors: Bauer Johann , Podack Eckhard R. , Valet Guenter 
Published: December 2022

Abstract
C5b-9 binding to erythrocyte membranes was quantitated with the aid of C7-depleted serum, reconstituted with 125-J-C7. The number of C5b-9 complexes/cell was correlated with the transformation of ghosts from the biconcave to the spheroid shape by the combination of flow cytometry and sucrose density gradient ultracentrifugation. At low complement levels the mean number of C5b-9 complexes ranged from 300 to 1200 complexes/erythrocyte ghost, and biconcave as well as spheroid ghosts were found simultaneously in the same sample. The separation of both types of ghosts by sucrose density gradient centrifugation showed that the irreversible transition from the biconcave to the spheroid form occurred at a critical value of 850 C5b-9 complexes/erythrocyte ghost. Ghosts bearing less than 850 C5b-9 complexes were biconcave, and resealed ghosts bearing more than 850 C5b-9 complexes were spheroid and leaky. The spheroid transition is abrupt; no intermediate forms could be detected. The spheroid transformation is interpreted as a direct interaction between the C5b-9 complexes and membrane proteins resulting in a disturbance of the cytoskeleton of the erythrocyte ghost followed by spheroidization.
The Activation of the Alternative Complement Pathway by Fetal Calf Serum and Mouse Thymocytes
Authors: Eisenberg Robert A. , Theofilopoulos Argyrios N. , Dixon F. J. 
Published: December 2022

Abstract
Mouse thymocytes activated the alternative complement pathway of mouse serum in the presence of heated fetal calf serum. The activation required C3 from the fetal calf serum but was independent of antibody either in the murine or bovine serum. No other murine cells tested, including erythrocytes, peripheral blood lymphocytes, lymph node cells, spleen cells, and various cultured cell lines, activated the alternative complement pathway as effectively as thymocytes. In addition, sera from species other than cows could not substitute for fetal calf serum. The C3 deposited on thymocytes was in the form of both C3b (immune adherence positive) and C3bi (conglutinable). We propose that the basis of activation in this system is the specific protection of bovine C3b on mouse thymocyte surface.
Insulin-Specific Murine Antibodies of Limited Heterogeneity
Authors: Kapp Judith A. , Strayer David S. , Robbins Paul F. , Perlmutter Roger M. 
Published: December 2022

Abstract
Immune responses by mice to porcine and bovine insulins are controlled by dominant genes linked to the H-2 gene complex. Mice bearing the H-2d haplotype respond to porcine insulin, whereas mice bearing other H-2 haplotypes do not; mice bearing the H-2b,d,v haplotypes respond to bovine insulin, whereas other strains do not. Analysis of serum antibody by isoelectric focusing demonstrates that antibodies specific for both porcine and bovine insulin are of restricted heterogeneity, suggesting that heterologous insulins stimulate a limited number of B cell clones. Banding patterns (spectrotypes) of sera from individuals of a given responder strain are remarkably uniform and these spectrotypic profiles are strain associated. In addition, phenotypic expression of spectrotypes is codominant in F1 hybrid mice and is controlled principally by allotype-linked genes. Analysis of cross-reactivity patterns demonstrates that all anti-porcine insulin antibodies bind bovine insulin and the majority of anti-bovine insulin antibodies bind porcine insulin. The minority of anti-bovine insulin antibodies that fails to bind porcine insulin may be specific for the A chain loop region of bovine insulin. These observations suggest that murine anti-insulin antibodies will provide a valuable model system for the identification of variable region genes that encode binding sites specific for protein molecules.
Increased Prostaglandin Production by Human Monocytes after Membrane Receptor Activation
Authors: Passwell Justen H. , Dayer Jean-Michel , Merler Ezio 
Published: December 2022

Abstract
Human monocytes in culture release small amounts of prostaglandin E (PGE) into the medium. Addition of Fc fragments of IgG to human monocyte monolayer cultures results in a marked increase in PGE release; Fab fragments, monomeric IgG, and human serum albumin have no effect. An IgG1 myeloma has no effect on PGE levels but addition of the heat aggregated protein results in a marked increase of PGE secretion. Exposure of the cells to Con A, which binds to a specific monocyte plasma membrane receptor, also results in a large increase in PGE release. The magnitude of the increase in PGE secretion produced by exposure of the monocytes to these ligands greatly exceeds the stimulation observed after the addition of antigen-activated mononuclear cell supernatants, zymosan, Sephadex beads, or endotoxin, to monocyte cultures. Prostaglandin E2 (PGE2) accounts for approximately 70% of the total prostaglandins released by stimulated cells.
After addition of Indomethacin to monocyte cultures, the stimulatory effects of the ligands on PGE release are inhibited. Addition of Con A to monocyte cultures results in an increased incorporation of [3H]-arachidonic acid into PGE2. These results suggest that this ligand stimulates synthesis as well as release of this prostaglandin.
A Role for Fatty Acid Composition of Complex Cellular Lipids in the Susceptibility of Tumor Cells to Humoral Immune Killing
Authors: Schlager Seymour I. , Ohanian Sarkis H. 
Published: December 2022

Abstract
Treatment of line-10 tumor cells with metabolic inhibitors (adriamycin, actinomycin D) or hormones (epinephrine, prednisolone) increases and decreases, respectively, the sensitivity of the cells to antibody-C mediated killing. Concomitantly, drug treatment inhibits the synthesis by the cells of specific complex lipids (cardiolipin, phosphatidyl choline, and triglycerides). Hormone treatment of these cells stimulates their synthesis of phosphatidyl choline and phosphatidyl serine and inhibits cardiolipin, phosphatidyl ethanolamine, and cholesteryl ester synthesis. Analysis of the newly synthesized fatty acids in the lipids extracted from drug-treated cells showed that the drug-induced sensitivity to antibody-C killing was accompanied by an increase in the amount of unsaturated fatty acids (C18:1, C18:2, and C18:3) in the cellular lipids. Cells washed free of drug and recultured in drug-free medium regained their resistance to antibody-C killing; these reverted cells had regained their ability to synthesize complex lipids and showed a fatty acid composition similar to that of untreated control cells. The effect of hormone treatment on the sensitivity of the cells to antibody-C killing could not be correlated with detectable changes in fatty acid synthesis. The results suggest that the drugs that increase the sensitivity of the cells to antibody-C killing may do so by altering the physical properties of the cell membrane through an effect on the synthesis of the fatty acid constituents of cellular lipids. Hormone treatment does not appear to affect the physical properties of the membrane by this mechanism.
Kinetic Analysis of Human Spontaneous Cell-Mediated Cytotoxicity
Authors: Pollack Sylvia B. , Emmons Sandra L. 
Published: December 2022

Abstract
We tested whether the kinetics of human spontaneous cell-mediated cytotoxicity (SCMC) fit the enzyme-substrate model for cellular cytotoxicity. As predicted by the model, the maximal rate of killing (Vmax) was proportional to the number of effector cells added, whereas the apparent affinity constant, K1/2, was a function of the source of effector cells, and remained unchanged when the number of effector cells was doubled. The linear initial velocity of lysis was maintained for only 90 min; thereafter, lysis proceeded at a lower rate. Thus the model strictly applies only during the initial phase.
Two lines of evidence suggested that NK cells that mediate SCMC function as recycling catalysts. Zone analysis of the log-dose relationship for SCMC indicated that effector cells are present in negligible amounts compared to the substrate. Although the rate of killing decreased with time, it appeared that each NK cell killed more than one target. When the same effector cell population was tested on two different targets, K562 and Chang, different K1/2 values were obtained. This result suggested that the two cell types are recognized differently, e.g., because they bear different determinants. Finally, we demonstrated formally that immune complexes competitively inhibit SCMC. If the enzyme-substrate analog holds, then FcR on NK cells are implicated either to be the “active site” for SCMC or to be closely linked to the active site.