bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bradykinin sensitization of colony-stimulating factor-1-responsive murine marrow progenitors to prostaglandin E. A property of the amino-terminal tetrapeptide fragment.
Authors: Moore R N , Duma E M , Bowersock T L 
Published: December 2022

Abstract
The active sequence in bradykinin (BK) responsible for PGE-aided inhibition of CSF-1-stimulated clonal proliferation of murine mononuclear phagocyte progenitors was determined. In total marrow cultures, BK and (D-Phe7)-BK, a specific BK antagonist, inhibited colony formation by CSF-1 responsive precursors that require two signals, CSF and LPS, for clonal proliferation. (Lys1)-BK, an inactive BK analogue with Lys substituted for the amino-terminal Arg, was inactive. Arg-Pro-Pro-Gly, the amino-terminal tetrapeptide fragment of BK, was fully capable, on a molar basis, of replacing either BK or (D-Phe7)-BK as an inhibitor. Bk, (D-Phe7)-BK, and Arg-Pro-Pro-Gly were not inhibitory for colony formation in cultures containing indomethacin or in cultures depleted of adherent marrow cells. However, in these cultures addition of 10(-9) M PGE2 fully restored inhibition of two-signal-dependent colony formation. PGE2-dependent inhibition by the three peptides was equivalent on a molar basis indicating that Arg-Pro-Pro-Gly contains the sequence responsible for this inhibitory effect of BK and is sufficient to exert PGE-dependent inhibition of two-signal-dependent colony formation. The two-signal-dependent progenitors appear to be in transition to CSF competence suggesting that BK and PGE produced in an hematopoietic environment may act together to limit the production of new macrophages by inhibiting progenitors in transition to CSF competence.
Synergistic action of phorbol ester and IL-3 in the induction of "connective tissue-type" mast cell proliferation.
Authors: Tsuji K , Nakahata T , Takagi M , Kobayashi T , Ishiguro A , Kikuchi T , Naganuma K , Koike K , Miyajima A , Arai K 
Published: December 2022

Abstract
12-O-Tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol ester, induced the proliferation of connective tissue-type mast cells (CTMC) synergistically with IL-3 in a methylcellulose culture, as well as with IL-4. The culture of single CTMC and the serum-free culture of CTMC fractionated by Percoll density gradient centrifugation showed that this synergistic action of IL-3 and TPA required no effects of accessory cells or other humoral factors. Although the populations of CTMC acted on by TPA and IL-4 seemed to be close to each other, the velocity of colony growth induced by the simultaneous stimulation of the combination of TPA and IL-4 was faster than that induced by either TPA or IL-4 in the presence of IL-3. In addition, the addition of anti-IL-4 antibody did not neutralize the effect of TPA on the proliferation of CTMC. These results suggest that TPA and IL-4 act on the proliferation of CTMC synergistically with IL-3 via a different pathway. Beside TPA, other phorbol derivatives capable of activating protein kinase C (PKC) induced the proliferation of CTMC synergistically with IL-3, but phorbol derivatives which were unable to activate PKC did not. These results indicate that the activation of PKC is involved in the process of TPA action on the proliferation of CTMC. Furthermore, the facts that 1-oleoyl-2-acetylglycerol, which activated membrane PKC transiently, and staurosporine, which has been reported to inhibit PKC, did not induce the proliferation of CTMC in the presence of IL-3 and that the effect of TPA was exhibited by the sustained stimulation suggest that the action of TPA on the proliferation of CTMC requires at least two steps. The first one is the primary activation of membrane PKC and the second one is the disappearance of PKC from the cells, "down-regulation."
IL-2 can enhance the cyclosporin A-mediated inhibition of Theileria parva-infected T cell proliferation.
Authors: Eichhorn M , Magnuson N S , Reeves R , Williams R O , Dobbelaere D A 
Published: December 2022

Abstract
The effect of cyclosporin A on the continuous proliferation of Theileria parva-infected T cells was tested and compared with its effect on the Con A-induced proliferation of bovine lymph node cells. The effect of rIL-2 on cyclosporin A-treated cells was also tested. Whereas the Con A-induced proliferation of bovine lymph node cells was completely inhibited by cyclosporin A, the continuous growth of T. parva-infected cells was only partly inhibited. In both cases the inhibition was accompanied by a reduction in the level of IL-2R/Tac mRNA and surface IL-2R expression. The cyclosporin A-mediated inhibition of Con-A stimulated lymphoblasts was, over a period of 5 days, largely abrogated by human rIL-2. In the short term, rIL-2 could also alleviate the growth inhibition of T. parva-infected cells caused by treatment with cyclosporin A. In the long term, however, rIL-2 enhanced the cyclosporin A-mediated inhibition of T. parva-infected cells, gradually leading to their complete growth arrest. This enhanced inhibition was accompanied by a further reduction in surface IL-2R expression, but not by a further decrease in the levels of steady state IL-2R/Tac mRNA. The fact that IL-2 can enhance the inhibition caused by cyclosporin A could be of relevance for the immunosuppressive activity of cyclosporin A.
Identification of enhancer-like elements in human IFN-gamma genomic DNA.
Authors: Ciccarone V C , Chrivia J , Hardy K J , Young H A 
Published: December 2022

Abstract
We have previously shown that transfection of a plasmid clone containing full length human IFN-gamma genomic DNA into a murine T-lymphoblastoid line is followed by basal expression of the transfected gene, with increased transcription occurring upon stimulation of the cells with either phorbol ester or IL-2. In addition, upon transfection of this DNA into murine fibroblasts, high level constitutive transcription was observed. In contrast to the results obtained under tissue culture conditions, introduction of the same DNA into the mouse germline resulted in tissue-specific expression of the transgene. We now report identification of a region 500-bp 5' of the human IFN-gamma TATAA box that has strong, PMA-inducible, enhancer-like activity when linked to a reporter gene (CAT) and transfected into a murine T cell line. However, when the same region of IFN-gamma genomic DNA was introduced into NIH-3T3 cells, no enhancer activity was detected either in the presence or absence of PMA. We have further found that an intronic region of the IFN-gamma genomic DNA (nucleotides 405-674) also contains enhancer activity that is functional in either fibroblasts or T cells. Enhancer activity of the intronic region is also PMA-inducible in the mouse T cells but constitutive in fibroblasts. Collectively, our observations suggest that control of human IFN-gamma gene expression is complex, involving noncontiguous regulatory domains in both 5' flanking and intronic regions of that gene.
Idiotype matching: correlation of expression of protective idiotype in sera with survival of tumor mice.
Authors: Chen J J , Saeki Y , Köhler H 
Published: December 2022

Abstract
A monoclonal anti-Id, 2F10, has previously been shown to protect against transfer of L1210/GZL tumor cells in DBA/2 mice and also to have therapeutic effects in mice with growing tumor. In this study we have measured expression of an idiotope which reacts with a tumor-protective anti-idiotypic antibody, 2F10, in the sera of mice bearing the L1210/GZL tumor. The levels of antibodies binding to 2F10, referred to as the "2F10 idiotope," are different in individual mice and also fluctuate over time. A statistical analysis demonstrated a significant correlation between these changes in 2F10 levels in mice with tumors and their survival times. Increasing 2F10 idiotope in sera of tumor mice correlated with long-term survival, whereas a decreasing trend was found in mice which died shortly after tumor transfer. Correlations between the 2F10 idiotope and survival were observed in groups of mice which had received surgery, cyclophosphamide, a combination of cyclophosphamide and anti-idiotype, or no treatment at all. No correlation between a nonrelated idiotope and survival was noted. Although 2F10 is an idiotope expressed by an anti-tumor-associated Ag antibody, the correlation between anti-tumor-associated Ag titers and survival was significantly lower than that between the 2F10 idiotope and survival. This demonstrates that 2F10 is preferentially associated with antibodies which are involved in tumor regression. Thus, the 2F10 idiotope in sera of tumor-bearing mice has predictive value for survival and tumor regression.
Identification and characterization of monoclonal antibodies specific for macrophages at intermediate stages in the tumoricidal activation pathway.
Authors: Paulnock D M , Lambert L E 
Published: December 2022

Abstract
Macrophage activation for tumor cell killing is a multistep pathway in which responsive macrophages interact sequentially with priming and triggering stimuli in the acquisition of full tumoricidal activity. A number of mediators have been identified which have activating capability, including in particular IFN-gamma and bacterial LPS. Although the synergistic functional response of normal macrophages to sequential incubation with these activation signals has been well-established, characterization of the intermediate stages in the activation pathway has been difficult. We have developed a model system for examination of various aspects of macrophage activation, through the use of the murine macrophage tumor cell line, RAW 264.7. These cells, like normal macrophages, exhibit a strict requirement for interaction with both IFN-gamma and LPS in the development of tumor cytolytic activity. In addition, these cells can be stably primed by the administration of gamma-radiation. In the studies reported here, we have used RAW 264.7 cells treated with IFN-gamma alone or with IFN-gamma plus LPS to stimulate the production of rat mAb probes recognizing cell surface changes occurring during the activation process. In this way we have identified three Ag associated with intermediate stages of the activation process. One Ag, TM-1, is expressed on RAW 264.7 cells primed by IFN-gamma or gamma-radiation. This surface Ag thus identifies cells at the primed cell intermediate stage of the tumoricidal activation pathway regardless of the mechanism of activation. A second Ag, TM-2, is expressed on IFN-treated RAW 264.7 cells but not on RAW 264.7 cells primed with gamma-radiation alone. Expression of this Ag can be induced by treatment of irradiated cells with IFN-gamma, but is not induced by IFN-gamma treatment of a noncytolytic cell line, WEHI-3. This Ag thus appears to be an IFN-inducible cell surface protein associated specifically with macrophage activation for tumoricidal activity. Finally, Ag TM-3 is detectable on RAW 264.7 cells primed by either IFN-gamma or gamma-radiation, after subsequent triggering of the primed cells with LPS. The addition of the mAb recognizing this antigen to the function assay of tumor cell killing can inhibit they lytic activity of both triggered cells. Thus, this Ag may play a role in the antitumor effector functions of activated macrophages. Overall, the results suggest that these mAb can serve as useful tools for identification of molecules associated with the process of macrophage activation for tumor cell killing.
Heterologous expression and epitope mapping of a human small nuclear ribonucleoprotein-associated Sm-B'/B autoantigen.
Authors: Rokeach L A , Jannatipour M , Hoch S O 
Published: December 2022

Abstract
The U snRNP associated B'/B polypeptides are primary targets of Sm autoantibodies in patients with systemic lupus erythematosus. We have bacterially expressed a Sm-B'/B autoantigen from Raji cells as a fusion with the anthranilate synthase protein from Escherichia coli. The recombinant Sm-B'/B fusion displays comparable immunologic reactivity to the native protein when tested with both monoclonal and polyclonal antibodies. To map Sm-B'/B epitopes, we constructed a series of 12 anthranilate synthase fusions spanning different regions of Sm-B'/B and tested such fusions on immunoblots against a panel of characterized sera. In this manner, we have identified six epitopes, five of which overlap the proline-rich carboxyl-terminus of the protein. Some of these epitopes appear to be conformational. The human sera tested can be divided, according to the epitopes they recognize, into six groups. Finally, we have shown that anti-Sm recognition of the (U1)RNP-specific A protein is attributable to cross-reactivity between the Sm-B'/B and A autoantigens.
Structural basis for variations in the sensitivity of human decay accelerating factor to phosphatidylinositol-specific phospholipase C cleavage.
Authors: Walter E I , Roberts W L , Rosenberry T L , Ratnoff W D , Medof M E 
Published: December 2022

Abstract
Human decay-accelerating factor (DAF) proteins expressed on E and nucleated cells differ in their susceptibility to phosphatidylinositol (PI)-specific phospholipase C (PLC) cleavage/release. To investigate the mechanism of this difference, the glycoinositol-phospholipid anchoring moieties of E DAF, and of HeLa cell, polymorphonuclear cell, and lymphocyte DAF were structurally compared. Labeling of PI-PLC-resistant E DAF with 3-(trifluoromethyl)-3-(m-[125I]-iodophenyl)-diazirine ([125I]TID) and TLC analysis of nitrous acid deamination anchor fragments showed a predominant phospholipid species with less polar migration than the 125I-TID-labeled PI. Gas chromatographic analyses of methanolyzed E protein revealed 2.20 +/- 0.16 mol of fatty acids [16:0, 18:0, 18:1, 20:4, 22:4, and 22:5 (0.76, 0.36, 0.25, 0.15, 0.40, 0.28 mol, respectively)] and 0.86 +/- 0.05 mol of inositol per mol of N-terminal Asp. Gas chromatography-mass spectroscopy demonstrated principally myo-inositol but also variable amounts of the chiro-isomer. Nondenaturing polyacrylamide gel electrophoresis of 14C-radiomethylated E protein revealed that pretreatment with hydroxylamine, a reagent which removes ester-linked lipids, rendered it PI-PLC susceptible. In contrast, parallel analyses of 35S-cys-labeled PI-PLC-sensitive HeLa DAF protein revealed only minor amounts of the hydroxylamine-sensitive phospholipid species. Similar results were obtained with 125I-surface-labeled DAF from polymorphonuclear cells, as well as from unstimulated peripheral blood and anti-CD3-activated lymphocytes. These findings demonstrate that, rather than PI, the E DAF anchor contains an inositol alkylacylglycerol-phospholipid which is heterogeneous with respect to acyl groups and inositol isomers, that an ester-linked substitution in this inositolphospholipid underlies the resistance of E DAF protein to PI-PLC cleavage/release, and that this structural modification is cell-specific.
Development of a diphtheria toxin mutant conjugate directed against antigen-specific B cells expressing high affinity surface Ig.
Authors: Marsh J W , Klinman D M 
Published: December 2022

Abstract
Modification of a mutant diphtheria toxin, possessing reduced binding capacity, with TNP groups resulted in an Ag-toxin conjugate capable of eliminating TNP-specific B cells. Previous experimental approaches to the elimination of Ag-specific B cells have involved the conjugation of Ag to holoricin molecules or ricin A chain. Holoricin conjugates possess efficacy, but display high nonspecific toxicity. A chain conjugates, which appear specific, lack high potency. In developing the diphtheria toxin-based conjugate, we found high potency for target anti-TNP hybridoma cells and for spleen cells isolated from TNP-immunized mice. The similar intoxication of nontarget cells required concentrations approximately three orders of magnitude higher. Additionally, it was found that the TNP-specific agent may have selectively depleted B cells producing high affinity IgG anti-TNP antibodies.
Alveolar macrophage function in rats with severe protein calorie malnutrition. Arachidonic acid metabolism, cytokine release, and antimicrobial activity.
Authors: Skerrett S J , Henderson W R , Martin T R 
Published: December 2022

Abstract
To investigate the effects of protein calorie malnutrition (PCM) on alveolar macrophage function, we measured antimicrobial activity, IL-1 and TNF production, and arachidonic acid metabolism in alveolar macrophages of infant rats with moderate and severe PCM. Groups of weanling male rats were fed a diet containing 0.8% protein (PCM) or 24% protein (control). A third group (pair fed) was fed limited amounts of the control diet that matched the mean daily dietary intake of the PCM group. After 4 wk on the diets, alveolar macrophages from all three groups functioned similarly with respect to surface adherence, phagocytosis and killing of Listeria monocytogenes, release of hydrogen peroxide and superoxide anion, and production of IL-1 and TNF. In contrast, Listeria-stimulated alveolar macrophages from the PCM group exhibited a marked shift in arachidonic acid metabolism, with impaired production of leukotriene B4 and enhanced release of thromboxane B2 and PGE2. The membrane arachidonic acid content and the uptake of [3H]arachidonate by alveolar macrophages did not differ among the three groups. The shift toward the cyclooxygenase pathway was not seen after 2 wk of dietary restriction and was reversed if PCM animals were fed the control diet for 1 wk. Thus, PCM does not affect the antimicrobial activity or cytokine production of alveolar macrophages, but causes alterations in arachidonic acid metabolism that may interfere with the modulatory functions of alveolar macrophages.
Regulation of C5a and formyl peptide receptor expression on human polymorphonuclear leukocytes.
Authors: Van Epps D E , Simpson S , Bender J G , Chenoweth D E 
Published: December 2022

Abstract
Fluorescein conjugates of C5a (FL-C5a) and formyl methionine-leucine-phenylalanine-lysine (FL-FMLPL) have been used to determine how the expression of receptors for these peptides is regulated on human polymorphonuclear leukocytes (PMN). Video intensification microscopy showed that receptors for FL-C5a were homogeneously distributed on the surface of the PMN, but within minutes were mobilized into patches and internalized by the PMN. Internalization of C5a receptors was confirmed in studies in which external FL-C5a fluorescence was quenched by reducing the pH. A similar rapid internalization was observed with FL-FMLPL. This process was inhibited for both fluorescent ligands by monensin. Reexpression of C5a and formyl peptide receptors after internalization occurred with both receptors. By comparison, the rate of reexpression of formyl peptide receptors was much faster than that observed with C5a receptors with the half maximal reexpression time for each being 5 to 10 min and 18 to 60 min, respectively. C5a receptor reexpression was completely blocked by monensin suggesting receptor recycling, whereas monensin had little effect on FMLPL receptor reexpression. The reexpression of both receptors occurred in the presence of cycloheximide indicating that this process occurred independent of protein synthesis. Additional studies on formyl peptide receptor showed that when PMN were treated with ionomycin to fully mobilize the intracellular pool of FMLPL receptors, receptor reexpression failed to occur. These studies show that both C5a and formyl peptide receptors are internalized after binding ligand, but that their reexpression occurs through different mechanisms. C5a receptors appear to be recycled to the cell surface whereas formyl peptide receptors are reexpressed predominantly by translocation from an intracellular pool.
T cell receptor junctional regions and the MHC molecule affect the recognition of antigenic peptides by T cell clones.
Authors: Sorger S B , Paterson Y , Fink P J , Hedrick S M 
Published: December 2022

Abstract
Nine independent pigeon cytochrome c-specific T cell clones were analyzed by using a panel of antigenic peptide analogs presented in association with three allelic IE-encoded MHC glycoproteins. Eight of the T cell clones expressed a TCR composed of a unique alpha- and beta-chain amino acid sequence, and concordantly, each of these T cell clones exhibited a unique Ag specificity. This was true for several clones which differed only in TCR V-J junctional regions. Interestingly, for a given clone, the response to some of the peptide analogs depended to a large extent on the allelic form of the presenting MHC molecule. A simple interpretation of these data would suggest that certain positions of the peptide Ag are most important for Ag-MHC molecule interactions, and that these specific interactions can influence the antigenic epitope recognized by the TCR. We suggest that an antigenic peptide binds to an MHC glycoprotein in a distinct way, but may retain a measure of flexibility.
Molecular cloning of cDNA that encode MHC class I molecules from a New World primate (Saguinus oedipus). Natural selection acts at positions that may affect peptide presentation to T cells.
Authors: Watkins D I , Letvin N L , Hughes A L , Tedder T F 
Published: December 2022

Abstract
To investigate the evolutionary pressures that drive the generation of polymorphism in primate MHC class I molecules, three cDNA that encode MHC class I alleles from a New World monkey, the cotton-top tamarin (Saguinus oedipus), were cloned and sequenced. These tamarin MHC class I alleles contained amino acid substitutions not found in any of the previously sequenced human MHC class I alleles. Moreover, the majority of these unique amino acid substitutions was located in the Ag recognition site at positions that have been shown to be critical in the presentation of viral peptides to T cells in mice and humans. These data suggest that selective pressures on MHC class I molecules preferentially act on the Ag recognition site and that the peptide binding or presenting functions of these molecules may drive the generation of MHC class I polymorphism. The novel Ag recognition sites of the tamarin MHC class I molecules, in addition to their restricted polymorphism, might account for the unusual susceptibility of the cotton-top tamarin to human pathogens.
Partial deletions of the cytoplasmic domain of CD2 result in a partial defect in signal transduction.
Authors: Bierer B E , Bogart R E , Burakoff S J 
Published: December 2022

Abstract
CD2 (T11, the T cell erythrocyte receptor or the SRBC receptor), a nonpolymorphic 47- to 55-kDa glycoprotein, appears to play a role in T lymphocyte adhesion, signal transduction, and differentiation. Pairs of anti-CD2 mAb induce T cell proliferation, suggesting that CD2 may be an Ag-independent pathway of T cell activation. We have expressed the human CD2 and a number of cytoplasmic domain deletion mutants of CD2 in an Ag-reactive murine hybridoma. We have previously shown that a cytoplasmic domain deletion mutant, CD2 delta B, in which the carboxyl-terminal 100 amino acids have been deleted, is no longer capable of signaling through CD2. Here we have expressed a second cytoplasmic domain deletion mutant, CD2 delta S, in which the terminal 41 amino acids have been removed, including the region with greatest conservation between the mouse, rat, and human species. CD2 delta S+ hybridomas were able to respond to Ag and to LFA-3 plus an anti-CD2 mAb. Although the CD2 delta S+ hybridomas responded comparably to the wild-type CD2+ hybridomas to certain pairs of anti-CD2 mAb (e.g., MT110 + 9-1 mAb), these CD2 delta S+ hybridomas were markedly deficient in their ability to respond to other pairs of stimulatory anti-CD2 mAb (e.g., 9.6 + 9-1 mAb). These data suggest that the cytoplasmic domain may have several functional regions, as partial deletions of the cytoplasmic domain appear to result in partial defects in signal transduction.