bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomous Growth of Human T-Lymphotropic Virus Type I Infected Human Lymphocytes Treated With N-methyl-N'-nitro-N-nitrosoguanidine and Ultraviolet Rays
Authors: Maruyama Koshi , Mochizuki Shigenobu , Kawamura Kiyoko , Tamayama Chieko 
Published: January 2018

Abstract
Human T-cell cultures infected with human T-lymphotropic virus type I (HTLV-I) and interleukin-2 (IL-2)-dependent for their continuous growth were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then maintained in the medium containing phorbol 12-myristate 13-acetate (TPA). Cells achieved independence from IL-2 but became TPA-dependent for continuous growth. Multiple ultraviolet (UV) irradiations of TPA-dependent cells resulted in their autonomous growth. G-band karyotype analysis revealed multiple chromosomal abnormalities that were seen in cells before and after MNNG treatment and UV irradiations, and those that were only seen in autonomously growing cells. Viral expression was found to be transiently enhanced in association with emergence of certain chromosomal changes. Exposure of HTLV-I infected cells to certain mutagens may promote the occurrence of the specific rearrangement of cellular genes responsible for regulation of cellular and viral replication and may lead these cells to neoplastic transformation.
Modulation of the Oxidative Burst in Trout Myeloid Cells by Adrenocorticotropic Hormone and Catecholamines: Mechanisms of Action
Authors: Bayne Christopher J , Levy Sharon 
Published: January 2018

Abstract
The oxidative burst of rainbow trout (Oncorhynchus mykiss) phagocytes was previously found to be differentially modulated by adrenocorticotropic hormone (ACTH) and the catecholamine receptor agonists phenylephrine and isoproterenol. From data obtained using both luminol-enhanced chemiluminescence (LECL) and ferricytochrome C (cyt C) reduction to measure oxidative burst kinetics, we postulated that the observed modulation was mediated by affects on enzymes responsible for the production and metabolism of superoxide anion. Using exogenous superoxide dismutase (SOD) and catalase as scavengers, nitroprusside to poison endogenous SOD, and an assay for hydrogen peroxide, we have tested our postulates by exploiting the differences with which various reactive oxygen intermediates influence LECL and cyt C reduction. The ability of ACTH to potentiate both assays of the oxidative burst appears due to its enhancing influence on the production of superoxide. Phenylephrine, an α-adrenergic receptor agonist, appears to enhance the activity of endogenous SOD, whereas isoproterenol, a β-adrenergic receptor agonist, may suppress SOD activity. This work reveals how components of the natural immune system may be regulated by products of the neuroendocrine system. Also, lymphocyte-derived ACTH may provide a novel pathway for lymphoid regulation of inflammation.
Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin
Authors: Shau Hungyi , Kim Anthony , Golub Sidney H 
Published: January 2018

Abstract
Natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxic functions can be strongly augmented by the iron-carrier protein lactoferrin (LF). LF significantly enhances NK and LAK activities when added at the beginning of NK or LAK cytotoxicity assays. LF is effective in augmenting cytotoxic activities at concentrations as low as 0.75 μg/ml, and higher concentrations of LF induce greater augmentation of NK and LAK. Iron does not appear to be essential for LF to increase NK and LAK, as depleting iron from LF with the chelator deferoxamine does not affect the capacity of LF to increase cytotoxicity. LF is known to have RNase enzymatic activity, and LF enhancement of NK and LAK can be blocked by RNA. However, LFs from two different sources with over 100-fold difference in RNase activity are equally effective in enhancing NK and LAK. Furthermore, purified non-LF RNase does not modulate NK or LAK activity and DNA is as effective as RNA in blocking LF augmentation of NK or LAK cytotoxicity. Therefore, the RNase activity is unlikely to be responsible for LF enhancement of the cytotoxicities. Newborn infants are known to have low NK activity and NK and LAK cells have been implicated in host defense against microbial infections. Thus, maternal milk-derived LF may have a role in boosting antimicrobial immunity in the early stages of life. In adults, LF released from neutrophils may enhance NK and LAK functions in the inflammatory process induced by microbial infections.
TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages
Authors: Santiago-Schwarz Frances , Belilos Elise , Diamond Barbara , Carsons Steven E 
Published: January 2018

Abstract
We describe dendritic cell progenitors within the CD34+ stem cell compartment in neonatal cord blood and identify growth factors contributing to their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF), although mainly promoting the growth and differentiation of monocyte-macrophages (mono-mφs), also induced the differentiation of cells with the distinctiv morphological features of dendritic cells (DCs). Tumo necrosis factor (TNF) in combination with GM-CSF promoted further growth of both cell types but most notably increased the DC content. In situ analysis revealed that the cells exhibiting DC morphology were positive for class II major histocompatibility complex antigens but were CD14 negative, did not exhibit nonspecific esterase activity, and were nonphagocytic. Moreover, the mixed leukocyte reaction stimulatory capacity of cultures with the higher DC content was greater. TNF, interleukin-1 (IL-1), IL-6, or platelet-derived growth factor (PDGF) was inactive in promoting stem cell proliferation or DC morphology. IL-1 or PDGF synergized with GM-CSF to increase mono-mφ–associated cell proliferation but did not increase the DC content. The development of a common DC-monocyte precursor was suggested by the presence of colony-forming unit–like clusters containing mono-mφ8 and DCs and one sharp proliferative peak. The loss of DC morphology after 21 days, coupled with increases in mono-mφ–associated markers and a constant number of viable cells, further suggests that DC morphology may fluctuate in culture or is a transient feature acquired by certain cells of the mono-mφ lineage.
Phorbol ester reduces constitutive nuclear NFχB and inhibits HIV-1 production in mature human monocytic cells
Authors: Mufson RA , Myers Carla , Turpin Jim A , Meltzer Monte 
Published: January 2018

Abstract
NFχB is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocyte leukemias. There is little information available on the response of NFχB to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NFχB binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NFXB in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NFχB from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SPI was unaffected by addition of TPA. The disappearance of NFXB from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NFXB species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NFχB. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NFχB and HIV-1 replication induced by phorbol esters in promonocyte leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.
Induction of a 26-kDa membrane-form tumor necrosis factor (TNF)-α in human alveolar macrophages
Authors: Nii Akihiko , Sone Saburo , Orino Etsuko , Ogura Takeshi 
Published: January 2018

Abstract
The expressions of a membrane form of TNF (m-TNF) by human alveolar macrophages (AM) and autologous blood monocytes from healthy donors were examined. Upon lipopolysaccharide (LPS) stimulation, AM produced 26-kDa TNF-α on their cell surface. We designed a bioassay for measuring m-TNF in which macrophages were fixed with paraformaldehyde after stimulation for 18 h, then m-TNF activity was assessed as cytotoxicity of fixed macrophages on L929 cells. This assay was specific to m-TNF because: 1) no soluble factors were contributed to the cytotoxicity of fixed AM, 2) anti-TNF-α monoclonal antibody completely neutralized m-TNF activity, and 3) m-TNF activity was not altered after low- pH or high-salt treatment. On LPS stimulation, AM produced significant amounts of m-TNF earlier than TNF-α secretion. AM also expressed significant amounts of m-TNF when stimulated with other bacterial components and their derivatives. Interleukin (IL)-4 suppressed both m-TNF production and TNF-α secretion. p-Toluene- sulfonyl-L-arginine methyl ester (TAME) inhibited specifically TNF-α secretion and not m-TNF expression. Although blood monocytes produced small amounts of m- TNF, monocyte-derived macrophages showed enhanced m-TNF after cultivation with GM-CSF for 10 days. These findings indicate that m-TNF is expressed as a step in the TNF-α producing system, and suggest that m-TNF may play important roles in exhibition of macrophage function in situ. J. Leukoc. Biol 53: 29–36; 1993.
Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages
Authors: Watanabe Shiro , Onozaki Kikuo , Yamamoto Shunsuke , Okuyama Harumi 
Published: January 2018

Abstract
Increasing die dietary α-linolenate (18:3n - 3)/linoleate (18:2n - 6) ratio results in an increase in lipopolysaccharide (LPS)-etimulated tumor necrosis factor (TNF) production in mouse resident and casein-induced peritoneal macrophages [3]. We found that prostaglandin E2 (PGE2) production is inversely related to TNF production and that indomethacin abolishes the effect of changing the essential fatty add balance in resident macrophages. The resident macrophages enriched in n - 3 did not produce a significant amount of PGE3. Accordingly, the decreased production of PGE2 appears to be a major negative regulatory factor for enhancement of TNF production in the it - 3 enriched resident macrophages. In casein-induced macrophages the situation is more complex. Indomethadn decreased PGE2 production and increased TNF production; however, the differences in TNF production between the it - 6 enriched and it - 3 enriched macrophages were not completely abolished by indomethadn treatment. Lysosomal add phosphatase activity, a marker of activation/maturation stages, was elevated in the it - 3 enriched compared to the it - 6 enriched casein-induced macrophages but was similar in the resident macrophages of the two dietary groups. Expression of CD 14, which is a receptor for LPS, was not different in casein-induced macrophages of the two dietary groups. Thus, the differences in production of TNF between the n- 3 and n - 6 enriched resident macrophages can he accounted for mostly by a difference in the production of a negative feedback effector, PGE2. However, a significant portion of the TNF production in casein-induced macrophages is regulated by a factor(s) other than PGE2 and LPS receptor; advanced activation/maturation stages induced by the diet high in α-linolenate may underlie the enhanced TNF production in casein-induced macrophages. J. Leukoc. Biol. 53: 151–156; 1993.
Optimization of peroxide production by resident macrophages
Authors: Cook-Mills Joan M , Fraker Pamela J 
Published: January 2018

Abstract
Previous reports indicated that resident macrophages produced low or nondetectable quantities of H2O2 (1—10 nmol H2O2/mg resident macrophage protein) when measured by the phenol red assay described by Pick and Mizel [5]. However, modifications of the assay that included addition of calcium to assay solutions, alterations in cell-harvesting methods, increasing the concentration of cells analyzed, incubating the cells in ambient air, and enhancing the interactions between macrophages and particulate stimulants by centrifugation resulted in increased production of peroxide. Each variable was instrumental in improving the assay conditions and the combination of changes dramatically increased the amount of peroxide (30-60 nmol H2O2/mg resident macrophage protein) obtained from murine resident macrophages, making it possible to better assess the role of these cells in microbicidal killing. J. Leukoc. Biol. 53: 205–207; 1993.
GTP-binding proteins in polymorphonuclear granulocytes of severely burned patients
Authors: Brom Joachim , Köller Manfred , Müller-Lange Petra , Steinau Hans Ulrich , König Wolfgang 
Published: January 2018

Abstract
In order to study the biochemical mechanism underlying the cellular dysfunctions of polymorphonuclear granulocytes (PMNs) from severely burned patients, we analyzed the role of GTP-binding proteins (G-proteins) in PMNs from 11 burned patients. Our data demonstrate a significant enhancement of the basal GTPase activity within unstimulated neutrophils of severely burned patients compared to cells from healthy donors. This enhancement was significant within 4 weeks after the trauma, followed by a return to control levels. The increase in GTPase activity correlated with enhanced expression of the small G-protein Ras and the regulatory Ras-GTPase activating protein (Ras-GAP) compared to that in healthy donor cells. However, expression of the Ras-related protein Rapl, which is involved in initiation of the respiratory burst, was reduced. The observed changes in G-protein activity and expression impair the signal transduction cascade as well as bacterial killing and may lead to high susceptibility toward infections and finally to septic conditions. J. Leukoc. Biol. 53: 268–272; 1993.
Differences in intracellular pool and receptor-dependent mobilization of the adhesion-promoting glycoprotein Mac-1 between eosinophils and neutrophils
Authors: Lundahl J , Halldén G , Hed J 
Published: January 2018

Abstract
Recruitment of cells to an inflammatory site is a process that is selectively regulated. At an inflammatory site caused by bacterial infection, predominantly neutrophil accumulation is observed. This is in contrast to air lergic inflammation, where predominantly eosinophil accumulation occurs. Mac-1 is an inducible adhesion molecule for both neutrophils and eosinophils. We examined the mobilization of this receptor on neutrophils and eosinophils after exposure to factors related to bacterial infections and allergic inflammation. We found more pronounced mobilization of Mac-1 on neutrophils than eosinophils after exposure to N-formylmethionyl- leucyl-phenylalanine, lipopolysaccharides, and activated sera (C5a). There was no significant difference in Mac-1 expression after exposure to aggregated immunoglobulin G. Incubation with interleukin-5 (IL-5) caused a significant increase of Mac-1 expression on eosinophils but not on neutrophils. Neutrophils seem to respond to a greater extent than eosinophils to factors related to bacterial infections, whereas eosinophils respond better to IL-5 associated with allergic inflammation. We measured the total pool of Mac-1 to evaluate whether these differences could depend on the size of the intracellular pool. Eosinophils had a larger total pool of Mac-1 than neutrophils. This finding increases the difference between eosinophils and neutrophils when relating the mobilized pool to the total pool. Stimulation with receptor- independent stimuli such as phorbol myristate acetate and ionomycin induced more pronounced mobilization of Mac-1 on eosinophils, but no differences were obtained if the mobilized pool was related to their total pool. These results indicate that the difference in responsiveness depends on different receptor-mediated signaling, since receptor-independent stimulation resulted in relatively similar mobilization of the intracellular pool of Mac-1. J. Leukoc. Biol. 53: 336–341; 1993.
C-reactive protein increases production of IL-1α, IL-1β, and TNF-α, and expression of mRNA by human alveolar macrophages
Authors: Rochemonteix Béatrice Galve-de , Wiktorowicz Krzysztof , Kushner Irving , Dayer Jean-Michel 
Published: January 2018

Abstract
The concentration of C-reactive protein (CRP) increases in human plasma up to a thousandfold during inflammatory states. Because tissue macrophages have been shown to have receptors for CRP, the question arises of whether these cells may respond to increased local concentrations of CRP by producing cytokines capable of participating in the inflammatory response. Accordingly, we examined the capacity of alveolar macrophages — relatively accessible human macrophages—to produce interleukin-1 (IL-1) and tumor necrosis factor a (TNF-α) in response to CRP. We found that production of IL-lα, IL-1β, and TNF-α, as measured by bioassay and immunoassay, increased in a dose-dependent manner after stimulation by CRP and that the levels of the respective mRNAs analyzed by Northern blot increased proportionally. These findings suggest that one of the fimctions of CRP may be to stimulate the production of IL-1 and TNF by macrophages at inflammatory sites where alterations of capillary permeability combined with an increased serum level lead to enhanced local concentrations of this acute-phase protein. J. Leukoc. Biol. 53: 439–445; 1993.
Analysis of the synergistic stimulation of mouse macrophage proliferation by macrophage colony-stimulating factor (CSF-1) and tumor necrosis factor a (TNF-α)
Authors: Guilbert Larry J , Winkler-Lowen Bonnie , Smith Anne , Branch Donald R , Garcia-Lloret Maria 
Published: January 2018

Abstract
Abstract: Tumor necrosis factor a (TNF-α) more than doubles tritiated thymidine ([3H]TdR) uptake in mouse macrophages stimulated by macrophage colony- stimulating factor (CSF-1). However, nothing is known of how TNF-α affects this increase or even whether it is manifested by increased cellular proliferation. Here we characterize the effects of TNF-α on CSF-l-stimulated proliferation of both primary cells (bone marrow-derived macrophages, BMMs) and a cloned growth factor-dependent macrophage cell line (SI). We show that the TNF- α-induced increase in [3H]TdR uptake of CSF-l-stimu- lated macrophages is directly proportional to an increase in the DNA content of the culture and that the effects of TNF-α are direct and independent of cell number. TNF-a decreases the population doubling time of log-phase growing macrophages having quite different growth rates to the same (approximately 30%) extent: the doubling time of BMMs decreases from 24 to 17 h and that of SI cells from 17 to 13 h. TNF-α exerts its effects on log-phase growth by increasing to the same proportion CSF-l-stimulated proliferation at all concentrations of CSF-1; that is, TNF-α does not shift, but rather amplifies, the CSF-1 dose-response curve. Although TNF-α alone does not stimulate macrophage proliferation, its presence in S1 cell cultures coming to quiescence after withdrawal of CSF-1 greatly increases subsequent CSF-l-stimulated [3H]TdR uptake as the cells reenter the cycle. Finally, we show that both human and mouse TNF-α increase CSF-l-stimulated log-phase growth and reentry of quiescent cells into the cycle equally on a molar basis (halfmaximal stimulation of approximately 0.3 nM). The latter observation argues that the growth-stimulatory effects of TNF-α are mediated via the 55-60-kd TNF receptor. We conclude that TNF-α acts directly on growth- competent macrophages to decrease significantly the population doubling time in a manner that enhances the mitogenic effects of CSF-1.
Countermeasures for ameliorating in-flight immune dysfunction
Authors: Fuchs Boris B , Medvedev Andrew E 
Published: January 2018

Abstract
We analyzed immune disturbances caused by the influence of spaceflight factors and proposed approaches for their correction. First, we determined the significant resistance of humoral immunity to the action of spaceflight factors, for example, B cell and immunoglobulin content, B cell reactivity to lipopolysac- charide, and distribution of B cell clones to trinitrophenyl (TNP group). A brief reversible increase of IgA and/or IgG concentration was the most characteristic shift observed. However, we noted prominent changes of T cells and natural killer (NK) cells, such as decreases in the content and phytohemagglutinin (PHA) reactivity of T lymphocytes, reduced T helper activity, and a reduction in NK cell cytotoxic activity in humans and animals during prolonged spaceflights. Rat bone marrow cells showed a decreased response to macrophage colony- stimulating factor. Studies with rat lymph node cells showed that microgravity and spaceflight stressors may influence lymphocytes in a tissue-specific manner. In experiments on isolated cells, human lymphocytes produced interferon more intensively in a reduced-gravity (microgravity) environment than under terrestrial conditions. However, lymphocyte activation by concanavalin A was sharply suppressed. Under microgravity conditions the transfer of activating signal to protein kinase C was strongly reduced. Thus, in-flight disturbances of T and NK cell functions are quite significant and could cause some diseases. However, to date the in-flight immune dysfunctions have not been excessive. Probably, we are mainly dealing with a complex of changes of immunity in space that is similar to that in the presence of acute stress. Therefore, it is reasonable to consider stress-related immunotherapy approaches in the practice of space medicine. The most effective methods and approaches of modern immunotherapy, such as artificial vaccines, monoclonal antibodies and immunoconjugates, recombinant cytokines, or immunomodulators etc, are also reviewed.
Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation
Authors: Endres Stefan , Meydani Simin N , Ghorbani Reza , Schindler Ralf , Dinarello Charles A 
Published: January 2018

Abstract
We studied the in vitro production of interleukin-2 in nine healthy volunteers who added 18 g/day of fish-oil concentrate rich in n-3 polyunsaturated fatty acids to their normal Western diet for a period of 6 weeks. Interleukin-2 synthesis from stimulated peripheral blood mononuclear ceils was suppressed from 6.2 ng/ml at baseline to 2.2 ng/ml 10 weeks after the end of n-3 fatty acid supplementation (65% decrease; P - .04). At the same time phytohemagglutinin-induced proliferation of mononuclear cells was suppressed by 70% from the presupplement level. Interleukin-2 production returned to the premedication level at the end of the studies. The results suggest that the effect of dietary n-3 fatty acids in some diseases may be mediated in part by decreased production of interleukin-2 and decreased mononuclear cell proliferation.