bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes for IFN-beta-2 (IL-6), tumor necrosis factor, and IL-1 are expressed at high levels in the organs of normal individuals.
Authors: Tovey M G , Content J , Gresser I , Gugenheim J , Blanchard B , Guymarho J , Poupart P , Gigou M , Shaw A , Fiers W 
Published: December 2022

Abstract
The gene of a cytokine designated IFN-beta-2, or IL-6, and recently identified as identical to the B cell-stimulatory factor 2, is transcribed at high levels in the spleen, liver, kidney, and peripheral blood leukocytes of normal individuals. The number of IFN-beta-2/IL-6 transcripts present endogenously in normal human tissues (0.6 to 16 copies/cell) is comparable to that present in normal cells induced in vitro with human rTNF. This is in marked contrast to the absence of detectable IFN-beta-1 transcripts (less than 0.0003 copy/cell) in the same samples of human tissue. The expression of the IFN-beta-2/IL-6 gene is closely associated with that of two other cytokines TNF, and IL-1. Thus, significant levels of IFN-beta-2/IL-6, TNF, IL-1 alpha, and IL-1 beta, mRNA were detected in all the samples of normal tissue tested and those samples which contained high levels of IFN-beta/IL-6 mRNA also contained high levels of TNF, and IL-1 beta mRNA. These results suggest that these cytokines may function in consort as regulators of cellular growth and function in normal tissues.
Inhibition by IL-1 of endothelial cell activation induced by tumor necrosis factor or lymphotoxin.
Authors: Cavender D E , Edelbaum D 
Published: December 2022

Abstract
Previous studies in this and other laboratories have demonstrated that IL-1, lymphotoxin (LT), and TNF rapidly stimulate a number of proinflammatory properties in cultured endothelial cells (EC) including cell-surface procoagulant activity and increased adhesivity for lymphocytes, monocytes, and polymorphonuclear leukocytes. In addition, we have demonstrated that LT and TNF, but not IL-1, stimulate increases in EC RNA synthesis, protein synthesis, and cellular volumes, changes which may correspond to the hypertrophy of EC seen at sites of inflammation in vivo. It is reported here that both human rIL-1 alpha and rIL-1 beta totally inhibit the increases in EC RNA synthesis, protein synthesis, and cell volumes induced by either TNF or LT. As little as 0.1 ng/ml of either IL-1 was sufficient to totally block the activation of EC induced by 100-fold higher concentrations (10 ng/ml) of either LT or TNF. The relevance of these findings to the regulation of inflammatory responses is discussed.
Perturbation of beta-glucan receptors on human neutrophils initiates phagocytosis and leukotriene B4 production.
Authors: Czop J K , Puglisi A V , Miorandi D Z , Austen K F 
Published: December 2022

Abstract
Normal human neutrophils were stimulated with the yeast cell wall product, zymosan, and examined for two biologic responses, ingestion of particles and production of leukotriene B4 (LTB4), under conditions that were comparable and optimal for the quantitation of each response. Monolayers of adherent neutrophils ingested unopsonized zymosan particles, at particle-to-cell ratios of 12.5:1 to 125:1, in a dose- and time-related manner. At a ratio of 125:1, the percentages of neutrophils ingesting greater than or equal to 1 and greater than or equal to 3 zymosan particles reached plateau levels of 55 +/- 6 and 32 +/- 9% (mean +/- SD, n = 8), respectively, within 30 min. At this same ratio, neutrophils during gravity sedimentation with zymosan particles synthesized LTB4 in a time-dependent manner for at least 45 min. The maximum amount of immunoreactive LTB4 released into supernatants was 3.8 +/- 1.2 ng per 10(6) neutrophils (mean +/- SD, n = 5) and the corresponding total immunoreactive LTB4 was 6.2 +/- 1.9 ng per 10(6) neutrophils. Treatment of 2 x 10(7) suspended neutrophils with 250 micrograms of trypsin for 20 min before concurrent assessment of neutrophil phagocytosis and LTB4 production reduced both of these responses by about 50%. Pretreatment of neutrophils with 800 micrograms/ml of soluble yeast beta-glucan inhibited their ingestion of zymosan by 84% (mean +/- SD, n = 3), with 50% inhibition occurring with 100 micrograms/ml of soluble beta-glucan; 800 micrograms/ml of soluble yeast alpha-mannan had no inhibitory effect. Pretreatment of neutrophils with 400 micrograms/ml of soluble yeast beta-glucan inhibited neutrophil synthesis of LTB4 by 90%, with 50% occurring with 200 micrograms/ml; 400 micrograms/ml of soluble yeast alpha-mannan had no inhibitory effect. The presence of 1.25 micrograms/ml of cytochalasin B during incubation with zymosan particles reduced neutrophil phagocytosis from 65 to 6%, and neutrophil synthesis of LTB4 from total levels of 6.0 +/- 0.3 ng/10(6) cells to zero (mean +/- SD, n = 3). Pretreatment with either cytochalasin B or vinblastine did not alter neutrophil generation of LTB4 induced by calcium ionophore. Neutrophils pretreated with vinblastine, at 4 x 10(-6) to 4 x 10(-4) M, and then maintained at one-half these concentrations during incubation with unopsonized zymosan particles exhibited no diminution in particle ingestion, but were markedly reduced in zymosan-induced synthesis of LTB4.(ABSTRACT TRUNCATED AT 400 WORDS)
Cloned L3T4+ T lymphocytes protect mice against Listeria monocytogenes by secreting IFN-gamma.
Authors: Magee D M , Wing E J 
Published: December 2022

Abstract
Murine T lymphocyte clones sensitized to Listeria monocytogenes were developed to investigate specific mechanisms of T cell-mediated immunity. The clones were of the Thy-1.2+, L3T4+, Lyt-2- phenotype and proliferated in a dose response fashion to heat-killed Listeria. Cloned T lymphocytes injected intravenously protected nonimmune mice against L. monocytogenes challenge as determined by spleen and liver bacterial numbers. Supernatants, produced by stimulating clones with heat-killed Listeria for 48 h, also afforded protection against L. monocytogenes. The clonal supernatants contained significant quantities of IFN-gamma and CSF. IFN-gamma production was Ag specific and occurred within 24 h of stimulation. CSF production by clones was increased four- to sixfold over baseline as determined by a bone marrow colony-forming assay and was Ag specific. When the IFN-gamma in supernatants was neutralized with a specific mAb, protection afforded by the supernatants was lost. These data indicate that one mechanism for Ag-specific, T lymphocyte-mediated protection against L. monocytogenes is the release of IFN-gamma.
Immunotherapy of established murine B cell lymphoma. Combination of idiotype immunization and cyclophosphamide.
Authors: Campbell M J , Esserman L , Levy R 
Published: December 2022

Abstract
A murine B cell lymphoma (38C13) was used to study the efficacy of idiotype immunotherapy against established tumors. Immunization of mice with 38C13 tumor-derived Ig, administered after a lethal tumor inoculation, significantly prolonged survival of animals compared to control groups. The efficacy of active immunotherapy was dramatically enhanced when combined with chemotherapy. Cyclophosphamide (100 mg/kg), administered in combination with idiotype immunization to mice bearing 10-day-old, 1 to 2 cm diameter s.c. tumors, resulted in a significant prolongation of survival as compared with either cyclophosphamide or immunization alone and yielded approximately 50% cures. Additional studies combining active immunotherapy with surgical excision of the primary s.c. tumor nodule were less effective than combination chemoimmunotherapy, indicating that reduction of tumor burden was necessary, but not sufficient for effective treatment of established 38C13 lymphoma.
Human vascular smooth muscle cells. Target for and source of tumor necrosis factor.
Authors: Warner S J , Libby P 
Published: December 2022

Abstract
TNF-alpha (also known as cachectin) may produce many of its important effects in vivo by actions on blood vessels. Endothelial cells are well known to respond to TNF-alpha. We investigated whether vascular smooth muscle cells (SMC), the most abundant cell type in most vessels, also respond to TNF-alpha and the related cytokine lymphotoxin (TNF-beta). Both human rTNF-alpha and beta (0.1 to 100 ng/ml) induced transient accumulation of IL-1 mRNA by adult human vascular SMC that peaked between 1 and 4 h. The inhibitor of RNA synthesis actinomycin D (1 microgram/ml) blocked the induction of IL-1 mRNA, whereas inhibition of protein synthesis with cycloheximide (1 microgram/ml) resulted in a marked "superinduction" of both IL-1 alpha and IL-1 beta mRNA species. TNF-alpha treatment also increased intracellular biologically active IL-1 and subsequent release of IL-1 activity from SMC. Metabolic labeling and immunoprecipitation with specific antibodies demonstrated de novo synthesis of IL-1 alpha and IL-1 beta precursors in TNF-treated or lymphotoxin-treated SMC. TNF-alpha also activated other SMC functions including the concentration-dependent release of PGE2 from SMC, and time-dependent induction of the gene for (2'-5')-oligoadenylate synthetase, an enzyme thought to mediate the anti-viral and anti-proliferative actions of IFN. We also explored whether SMC, which both produce and respond to IL-1, might also express either of the TNF genes. Bacterial LPS (10 micrograms/ml) caused slight accumulation of TNF-alpha transcripts. Incubation of SMC for 4 h with inhibitors of protein synthesis alone caused little or no elevation of TNF-alpha mRNA, but simultaneous addition of LPS ("superinduction" conditions) induced large amounts of TNF-alpha (but not TNF-beta) mRNA. Cells treated with anisomycin (1 microgram/ml) and LPS, then washed to remove this reversible inhibitor of protein synthesis, released TNF-alpha into the medium, as assessed by the L929 cytotoxicity assay and by metabolic labeling and immunoprecipitation. Thus, SMC both respond to both TNF and lymphotoxin and can produce TNF-alpha, a cytokine with numerous effects on vascular cells of potential significance in the pathophysiology of septic shock and other inflammatory conditions.
Establishment of a leukemic cell model for studying human pre-B to B cell differentiation.
Authors: Wörmann B , Anderson J M , Liberty J A , Gajl-Peczalska K , Brunning R D , Silberman T L , Arthur D C , LeBien T W 
Published: December 2022

Abstract
Reproducible models for examining early stages of human B cell differentiation are poorly developed. We now describe the establishment and characterization of a novel human leukemic cell line that recapitulates the pre-B to B cell stage of differentiation. This cell line, designated BLIN-1, was initially established in tissue culture medium containing low m.w. B cell growth factor, and consistently shows a dependency on this cytokine for optimal growth at low density. BLIN-1 cells have a 9p chromosomal abnormality, identical to the abnormality present in the leukemic blasts from the patient's original bone marrow aspirate. The immunologic phenotype of BLIN-1 is consistent with a cell arrested at the pre-B cell stage of development. Analysis of Ig gene rearrangement and Ig expression in a series of BLIN-1 subclones show that the cells spontaneously rearrange kappa light chain genes, leading to the differentiation of surface kappa-negative pre-B cells into surface kappa-positive B cells. The BLIN-1 cell line is, to our knowledge, the first defined human model for examining this critical developmental stage in human B cell ontogeny. As such, it offers a unique resource for examining variables influencing onset of kappa L chain gene rearrangement and expression.
IL-1 and TNF transmodulate epidermal growth factor receptors by a protein kinase C-independent mechanism.
Authors: Bird T A , Saklatvala J 
Published: December 2022

Abstract
The effect of the human rIL-1 alpha and rTNF-alpha on the binding of 125I-labeled epidermal growth factor ([125I]EGF) to its receptor (EGF-R) has been studied in human gingival fibroblasts (HuGi). Incubation of these cells with recombinant cytokines at 37 degrees C caused a rapid, dose-dependent decrease in their ability to subsequently bind subsaturating levels of [125I]EGF at 4 degrees C. Inhibition was evident at 5 min after addition of cytokines, reached a maximal level (60-70% reduction) after 15 to 30 min, and declined thereafter. Normal EGF binding was attained by 2 h. Half-maximal inhibition of EGF binding occurred at 10 pM IL-1 and 50 pM TNF. The two cytokines were not additive in their effect. Competition experiments at 4 degrees C showed that the cytokines did not interact directly with EGF-R; Scatchard analysis of binding of [125I]EGF to HuGi after treatment with IL-1 and TNF revealed an increase in EGF-R Kd from 0.75 nM to 2.9 nM with no change in receptor number. The effect of IL-1 and TNF on EGF-R was compared with that of the tumor-promotor PMA which is known to "transmodulate" EGF-R affinity by activating protein kinase C which then phosphorylates EGF-R. PMA caused a greater inhibition of EGF binding to HuGi (80 to 85% inhibition; ED50 = 500 pM), and recovery of binding was much slower. Importantly, in HuGi made deficient in protein kinase C by prolonged incubation with PMA, addition of fresh PMA no longer affected EGF binding, while the response to IL-1 and TNF was intact. Cytokine- but not PMA-mediated EGF-R transmodulation was partially reversed by treatment of the cells with millimolar concentrations of the kinase inhibitor amiloride. HuGi were incubated with H3 32PO4, stimulated with PMA or cytokines, and EGF-R were immunoprecipitated; IL-1 and TNF, like PMA, caused a 2- to 5-fold increase in receptor phosphorylation. We conclude that occupation of IL-1 and TNF-R activates a protein kinase, distinct from kinase C, for which EGF-R is a substrate.
Complement attack of altered outer membrane areas synthesized after inhibition of the 3-deoxy-D-manno-octulosonate pathway leads to cell death.
Authors: Goldman R C , Miller M F 
Published: December 2022

Abstract
Salmonella typhimurium containing specific genes coding for either temperature-sensitive (TS) 3-deoxy-D-manno-octulosonate (KDO) 8-phosphate synthetase or TS cytidine monophosphate-KDO synthetase grow normally when incubated at 30 degrees C and are resistant to C-mediated killing. However, bacteria become avirulent and sensitive to C-mediated killing upon thermal inhibition of TS KDO-8-phosphate synthetase (incubation at 38 degrees C) or TS cytidine monophosphate-KDO synthetase (incubation at 42 degrees C). Such thermal inhibition concurrently causes synthesis of an altered outer membrane which we now show is the site that renders cells susceptible to C-mediated killing. After incubation of cells in serum, the altered outer membrane area contains C9 in a trypsin-resistant state and membrane attack complex (MAC) lesions observable by electron microscopy. Trypsin-resistant C9 and MAC lesions were also observed in the inner membrane fraction from such serum-treated cells. In contrast, little C9 and few MAC lesions were associated with unaltered outer membrane areas present on these same serum treated cells. Control cells, grown at 30 degrees C and treated with serum (1) bound one-fifth as much C9 as was bound to cells incubated at 42 degrees C, (2) contained only a rare MAC lesion in the outer membrane, and (3) no observable MAC lesions in the inner membrane. We conclude that the altered outer membrane area is the site that renders cells susceptible to insertion of the MAC into both the outer and inner membrane resulting in cell death.
Role of lymphokine-secreting CD8+ T cells in cytotoxic T lymphocyte responses against vaccinia virus.
Authors: Mizuochi T , Hügin A W , Morse H C , Singer A , Buller R M 
Published: December 2022

Abstract
The present study has examined the relative role of CD4+ and CD8+ Th cells in the generation and reactivation of antivaccinia virus memory CTL responses. We show that mice primed in vivo to vaccinia virus generate in vitro antivaccinia virus memory CTL responses through both CD4+ and CD8+ Th cell pathways, with the CD4+ Th pathway being the more prominent of the two. In addition, we show that vaccinia virus-specific CD8+ Th cell function is mediated through production of lymphokines, including IL-2, and that the CD8+ Th cell component in the CTL response is labile, decreasing progressively with increasing time after in vivo priming. Thus, this study demonstrates the existence of two phenotypically distinct Th cell pathways in the generation of antivirus CTL responses.
Analysis of gene structure and antigen determinants of DR2 antigens using DR gene transfer into mouse L cells.
Authors: Kawai J , Ando A , Sato T , Nakatsuji T , Tsuji K , Inoko H 
Published: December 2022

Abstract
Three HLA class II DR beta genes and one DR alpha gene from the DR2 haplotype were cloned in cosmid vectors. The DR beta II gene might be a pseudogene lacking the first exon that encodes the leader peptide. The DR beta I and DR beta III genes were expressed, together with the DR alpha-chain, after transfection into mouse L cells. Restriction enzyme mapping of the DR beta genomic clones and reactivity of their products expressed on the L cell transfectant against mAb showed that the DR beta I and DR beta III genes encoded the nonpolymorphic and polymorphic DR beta chain, respectively. This arrangement is the reverse of that observed in other haplotypes, such as DR3, 4 and 6. The alignment of the HLA class II genes including the DR beta genes on the chromosome 6, however, was consistent with other haplotypes, e.g., centromere-DX beta-DX alpha-DV beta-DQ beta-DQ alpha-DR beta I-DR beta II- DR beta III-DR alpha-telomere. These results suggest that the susceptibility to mutations or gene conversions responsible for genetic polymorphisms depends on the gene itself and not on its location. Furthermore, absorption experiments of anti-DR2 allosera by the DR alpha/DR beta transfectants revealed that the so-called DR2 specificities were determined by multiple epitopes although both the DR beta I and DR beta III genes behaved similarly with DR2-specific antibodies.
Structural analysis of peptides capable of binding to more than one Ia antigen.
Authors: Sette A , Buus S , Colon S , Miles C , Grey H M 
Published: December 2022

Abstract
The Ia binding regions were analyzed for three unrelated peptide Ag (sperm whale myoglobin 106-118, influenza hemagglutinin 130-142, and lambda repressor protein 12-26) for which binding to more than one Ia molecule has previously been demonstrated. By determining the binding profile of three separate series of truncated synthetic peptides, it was found that in all three cases the different Ia reactivities mapped to largely overlapping regions of the peptides; although, for two of the peptides, the regions involved in binding the different Ia specificities were distinct. Moreover, subtle differences were found to dramatically influence some, but not other, Ia reactivities. Using a large panel of synthetic peptides it was found that a significant correlation exists between the capacity of peptides to interact with different alleles of the same molecule (i.e., IAd and IAk), but no correlation was found with the capacity of peptides to interact with different isotypes within the same haplotype (i.e., IAd and IEd). These data suggest that different alleles of the same MHC molecule may actually recognize closely related structures, whereas different isotypes may recognize unrelated, albeit non-mutually exclusive, structures on an Ag molecule.
Thymus transplantation and disease prevention in the diabetes-prone Bio-Breeding rat.
Authors: Georgiou H M , Bellgrau D 
Published: December 2022

Abstract
Bio-Breeding rat T lymphocytes proliferate poorly in response to alloantigen. Transplantation of Bio-Breeding rats with fetal thymus tissue from diabetes resistant rats leads to an improvement in the T cell proliferative response, but only if the thymus contains bone marrow-derived, radiation-resistant thymic antigen presenting cells of the diabetes-resistant phenotype. The current study provides evidence that thymus transplantation leading to the restoration of Bio-Breeding T cell proliferative function can also significantly reduce the incidence of insulitis and prevent the development of diabetes. It appears that a defect in the bone marrow-derived thymic APC population contributes to an abnormal maturation of Bio-Breeding T lymphocytes which in turn predisposes animals to insulitis and diabetic disease.
Thiol-sensitive mast cell lines derived from mouse bone marrow respond to a mast cell growth-enhancing activity different from both IL-3 and IL-4.
Authors: Hültner L , Moeller J , Schmitt E , Jäger G , Reisbach G , Ring J , Dörmer P 
Published: December 2022

Abstract
A series of permanent IL-3-dependent cell lines have been established from normal BALB/c or C3H bone marrow using alpha-thioglycerol-supplemented culture medium and PWM-stimulated spleen cell-conditioned medium as a source of IL-3. The cell lines and derivatives cloned in agar resembled "mucosal type" mast cells with respect to phenotypic and functional properties. In this report we demonstrate that in vitro growth of these mast cell lines was not only dependent on IL-3 and synergistically enhanced by IL-4, but in addition regulated by alpha-thioglycerol which could be replaced by 2-ME or cysteamine. We show that these thiol-sensitive mast cell lines respond to a mast cell growth enhancing activity (MEA) present in spleen cell-conditioned medium and acting in concert with IL-3. Partially purified MEA was not able to stimulate the growth of IL-3-dependent 32Dcl.23 cells, IL-2-dependent CTLL-2 cells or the mouse T cell line F4/4K.6 (L3T4+) adapted to grow in purified IL-4. Moreover, 11B11 hybridoma-derived anti-IL-4 mAb specifically neutralizing mouse Il-4 were unable to abolish the bioactivity of MEA. PWM, CSF-1, GM-CSF, IL-1, IL-2, IL-5, IL-6, IL-7, IFN-gamma, TGF-alpha, TNF-alpha, NGF, or EPO did not substitute for MEA in our standard proliferation assay.
Identification of high affinity receptors for vasoactive intestinal peptide on human lymphocytes of B cell lineage.
Authors: O'Dorisio M S , Shannon B T , Fleshman D J , Campolito L B 
Published: December 2022

Abstract
Specific, high affinity receptors for vasoactive intestinal peptide (VIP) have been identified on a human pre-B cell line, Nalm 6, and on a human plasma cell line, Dakiki. The single class of high affinity sites exhibited a KD of 12.6 +/- 2.9 nM for VIP in Nalm 6 cells and 9.1 +/- 2.7 nM in Dakiki plasma cells. The homologous peptides, peptide histidine methionine (PHM), growth hormone releasing factor (GHRF), and secretin were all less effective than VIP in competitively inhibiting binding of 125I-VIP to Nalm 6 and Dakiki plasma membranes. The putative receptor was characterized as a 47-kDa protein using covalent cross-linking techniques and VIP stimulated adenylate cyclase in pre-B cells. Human lymphocytes of B cell lineage thus appear to express functional VIP receptors homologous to the receptor identified in T lymphoblasts, brain, pituitary, and intestine.