bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic factors influencing murine hematopoietic productivity in culture
Authors: Phillips Robert L. , Couzens Matthew S. , Van Zant Gary 
Published: February 2005

AbstractIn order to study a previously described genetic difference manifested in stem cell kinetics of specific mouse strains, effects of this putative gene, stk, were measured on growth and expansion of stem and progenitor cell populations ex vivo. Bone marrow cells from each of two inbred mouse strains, C57BL/6J and DBA/2J, were placed into separate bioreactor cultures perfused continuously with growth medium containing erythropoietin (Epo), interleukin‐3 (IL‐3), granulocyte‐macrphage colony stimulating factor (GM‐CSF), and Kit ligand as well as 5% CO2. Expansion of cell numbers reached 20‐fold for DBA/2J and 10‐fold for C57BL/6J marrow within about 1 week of culture. Significant production was also seen of colonyforming unit (CFU)‐GM (up nine‐fold from input levels) just prior to the cell production peak, and, importantly, moderate expansion of day 12 colony‐forming unit‐spleen (CFU‐S; two‐ to threefold) occurred as well, although CFU‐S production peaked at a relatively short 4 days. CFU‐S and CFU‐GM levels declined rapidly in culture, either because of unfavorable growth conditions or terminal differentiation. Attempts to remove toxic metabolites by increasing the media perfusion rate resulted in a boost in cell expansion capability by DBA/2J marrow. In bioreactors in which stromal cells were established before marrow inoculation, there was greater expansion of CFU‐S (especially by DBA/2J) and CFU‐GM, although total cell yield appeared to be unaffected, perhaps because the maximum cell density had already been reached. The relative high potential for CFU‐S expansion measured in DBA/2J marrow over that of C57BL/6J will be useful in following genetic contributions to bone marrow production capacity. © 1995 Wiley‐Liss, Inc.
Insulin‐like growth factor I receptor is required for the mitogenic and transforming activities of the platelet‐derived growth factor receptor
Authors: Deangelis Tiziana , Ferber Andres , Baserga Renato 
Published: February 2005

AbstractR− cells are 3T3‐like cells derived from mouse embryos in which the insulin‐like growth factor I (IGF‐I) receptor (IGF‐IR) genes have been disrupted by targeted homologous recombination. These cells cannot grow in serum‐free medium supplemented by the growth factors that sustain the growth of other 3T3 cell lines, and cannot be transformed by oncogenes that easily transform wild type mouse embryo cells. We have used these cells to study the role of the IGF‐IR in the growth and transformation of cells overexpressing the platelet‐derived growth factor (PDGF)‐b̃b̃ receptor. We report that an overexpressed PDGF‐b̃b̃ receptor fails to induce mitogenesis or transformation in cells lacking the IGF‐IR, while capable of doing so in cells expressing the IGF‐IR. We conclude that the ability of the activated PDGF‐b̃b̃ receptor to stimulate cell proliferation and transformation requires a funcitional IGF‐IR. © 1995 Wiley‐Liss, Inc.
Macrophage colony‐stimulating factor induces thrombospondin I production by cultured human macrophages
Authors: De Nichilo Mark O. , Burns Gordon F. 
Published: February 2005

AbstractThe role of colony‐stimulating factors (CSFs) in regulating the synthesis of thrombospondin 1 (TSP1) by cultured human macrophages is investigated. Macrophage (M)‐CSF is shown rapidly and transiently to induce two predominant species of TSP1 mRNA. One of these species was 3.2 kb in size and appeared to be specific to M‐CSF‐stimulated macrophages. Adherent M‐CSF‐treated macrophages are also shown to express abundant surface cell‐associated TSP rapidly when examined by indirect immunofluorescence staining. Granulocyte‐macrophage (GM)‐CSF induced TSP1 mRNA at a later time point, and this was attributable to the effects of endogenous M‐CSF induced by the GM‐CSF; the GM‐CSF‐treated cells did not display surface‐associated TSP after 3 hr of treatment. Analysis of the TSP1 protein synthesised by the M‐CSF‐treated macrophages revealed the expected trimeric form of the molecule. In addition, an unidentified 95‐kDa protein was found to be covalently associated with immunoreactive TSP1, and this appeared to be specific to the macrophages as it was not found in TSP1 precipitated from other cell types. It is suggested that the induction of TSP1 by M‐CSF may play an important role in the major physiological functions of macrophages. © 1995 Wiley‐Liss, Inc.
Hydrocortisone regulation of hyaluronan metabolism in human skin organ culture
Authors: Ågren Ulla M. , Tammi Markku , Tammi Raija 
Published: February 2005

AbstractWe studied the influence of hydrocortisone (HC) on hyaluronan (HA) metabolism in explants of human skin, a model retaining normal three‐dimensional architecture of dermal connective tissue and dynamic growth and stratification of epidermal keratinocytes. The synthesis of hyaluronan and proteoglycans (PGs), and DNA, were determined with 3H‐glucosamine and 3H‐thymidine labelings, respectively. The total content and histological distribution of hyaluronan was studied utilizing a biotinylated aggrecan‐link protein complex. A low concentration of HC (10−9 M) stimulated the incorporation of 3H‐glucosamine into hyaluronan in epidermis by 23% and reduced the disappearance rate of hyaluronan by 25% in chase experiments, resulting in a 74% increase in total hyaluronan (per epidermal dry weight) after a 5‐day culture in 10−9 M HC. On the other hand, a high concentration of HC (10−5 M) reduced both synthesis (‐42%) and degradation (‐46%) of epidermal hyaluronan during 24 h labeling and chase periods. The cumulative effect of a 5‐day treatment was a 24% decrease of total epidermal hyaluronan. The high dose (10−5 M) also reduced keratinocyte DNA synthesis and epidermal thickness. In dermis, only the high (10−5 M) concentration of HC was effective, inhibiting the incorporation of 3H‐glucosamine into hyaluronan by 28%. No significant influences on total hyaluronan content or the disappearance rate of hyaluronan in dermal tissue was found. All HC concentrations lacked significant effects on newly synthesized PGs in epidermal and dermal tissues, but reduced the labeled PGs diffusing into culture medium. A low physiological concentration of HC thus maintains active synthesis and high concentration of hyaluronan in epidermal tissue, while high pharmacological doses of HC slows hyaluronan turnover and reduces its content in epidermis, an effect correlated with enhanced terminal differentiation, reduced proliferation rate and reduced number of vital keratinocyte layers. © 1995 Wiley‐Liss, Inc.
Competition between c‐fos and 1,25(OH)2 vitamin D3 in the transcriptional control of type I collagen synthesis in MC3T3‐E1 osteoblastic cells
Authors: Kuroki Yasuo , Shiozawa Shunichi , Kano Junichi , Chihara Kazuo 
Published: February 2005

AbstractInteraction between c‐fos and 1,25(OH)2 vitamin D3 (VD) on the type I collagen synthesis was studied. VD inhibited collagen synthesis and type I collagen mRNA expression in MC3T3‐E1 osteoblastic cells. In contrast, VD reversed the inhibition of collagen synthesis and mRNA expression of the c‐fos transfectants that overexpressed c‐fos gene to a comparable level as those of the control transfectants. The gel shift assay showed that vitamin D receptor (VDR) complex binding to vitamin D responsive element (VDRE) was inhibited under constitutively expressed c‐fos gene, suggesting that c‐fos gene product, c‐Fos, may inhibit the binding of VDR complex to VDRE by making a c‐Fos‐VDR complex. The result suggests the existence of a fine tuning between c‐fos and VD in the bone metabolism which may be relevant to the pathogenesis of rheumatoid bone lesion. © 1995 Wiley‐Liss, Inc.
Laminarin sulfate mimics the effects of heparin on smooth muscle cell proliferation and basic fibroblast growth factor‐receptor binding and mitogenic activity
Authors: Miao Hua‐Quan , Ishai‐Michaeli Rivka , Peretz Tamar , Vlodavsky Israel 
Published: February 2005

AbstractHeparin and heparin‐like molecules may function, apart from their effect on hemostasis, as regulators of cell growth and neovascularization. We investigated whether similar effects are exerted by laminarin sulfate, an unrelated polysulfated saccharide isolated from the cell wall of seaweed and composed of chemically O‐sulfated b̃‐(1,3)‐linked glucose residues. Laminarin sulfate exhibits about 30% of the anticoagulant activity of heparin and is effective therapeutically in the prevention and treatment of cerebrovascular diseases. We characterized the effect of laminarin sulfate on interaction of the heparin‐binding angiogenic factor, basic fibroblast growth factor (bFGF), with a naturally produced subendothelial extracellular matrix (ECM) and with cell surface receptor sites. Laminarin sulfate (1‐2 m̈g/ml) inhibited the binding of bFGF to ECM and to the surface of vascular smooth muscle cells (SMC) in a manner similar to that observed with heparin. Likewise, laminarin sulfate efficiently displaced both ECM‐and cell‐bound bFGF at concentrations as low as 1 m̈g/ml. Both laminarin sulfate and heparin efficiently induced restoration of bFGF receptor binding in xylosyltransferase‐deficient CHO cell mutants defective in initiation of glycosaminoglycan synthesis. Moreover, laminarin sulfate elicited bFGF receptor activation and mitogenic response in heparan sulfate(HS)‐deficient, cytokine‐dependent lymphoid cells. These results indicate that laminarin sulfate effectively replaced the need for heparin and HS in the induction of bFGF receptor binding and signaling. In other experiments, laminarin sulfate was found to inhibit the proliferation of vascular SMC in a manner similar to that observed with heparin. These effects of laminarin sulfate may have potential clinical applications in diverse situations such as wound healing, angiogenesis, and atherosclerosis. © 1995 Wiley‐Liss, Inc.
Induction of angiogenesis by smooth muscle cell‐derived factor: Possible role in neovascularization in atherosclerotic plaque
Authors: Kuzuya Masafumi , Satake Shosuke , Esaki Teiji , Yamada Kazuyoshi , Hayashi Toshio , Naito Michitaka , Asai Kanichi , Iguchi Akihisa 
Published: February 2005

AbstractThe development of atherosclerotic plaque is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of intraplaque hemorrhage. However, the mechanism and stimulus for neovascularization in atherosclerotic plaque are unknown. We postulated that smooth muscle cells (SMCs), a major cellular component in the vascular wall, might contribute to the induction of neovascularization in atherosclerotic plaque through the secretion of an angiogenic factor. We observed that endothelial cells (ECs) cultured on collagen gel with SMC‐conditioned medium became spindle shaped, invaded the underlying collagen gel, and organized a capillary‐like branching cord structure in the collagen gel. The conditioned medium also stimulated EC proliferation and increased the EC‐associated plasminogen activator activity. The angiogenic factor in SMC‐conditioned medium was retained in a heparin‐Sepharose column and eluted with 0.9 M NaCl. Neutralizing anti‐vascullar endothelial growth factor (VEGF) antibody attenuated the angiogenic activity in the conditioned medium, including the induction of morphologic changes in ECs, mitogenic activity, and increased plasminogen activator activity associated with ECs. Immunoblotting analysis confirmed the secretion of VEGF from SMCs. These observations indicate that SMC may be responsible for the neovascularization in atherosclerotic plaque through the secretion of VEGF. © 1995 Wiley‐Liss, Inc.
Insulin‐like growth factor‐1 stimulates amino acid uptake by the cultured human placental trophoblast
Authors: Karl Peter I. 
Published: February 2005

AbstractAmino acid uptake by the human placenta is known to occur via several transport mechanisms. However, regulation by extracellular factors has received relatively little attention. A recent report by this laboratory characterized the uptake of α‐aminoisobutyric acid (AIB) stimulated by insulin in the cultured human placental trophoblast The current study evaluated the effect of insulin‐like growth factor‐1 (IGF‐1) on AIB uptake in cultured human placental trophoblasts. Na+‐dependent AIB uptake was significantly stimulated by IGF‐l in a time‐dependent manner, as early as 30 min after hormone exposure. The maximum effect was at 2–4 hr of continuous exposure to IGF‐l and the stimulation was dependent upon IGF‐1 concentration approaching maximal stimulation at 50 ng.ml−1. AIB uptake was inhibited by increasing concentrations of α‐(methylamino)isobtyric acid (MeAIB). Approximately 75% of basal (unstimulated) Na+‐dependent AIB uptake was inhibited by MeAIB. The IGF‐1‐stimulated increment above basal AIB uptake was completely inhibited by MeAIB. IGF‐1 increased the maximum uptake yelocity but not Km. Using equimolar concentrations, stimulation was greater with IGF‐1 then with IGF‐2. Stimulation by IGF‐1, but not insulin, was inhibited by anit‐IGF‐1 receptor antibody, indicating mediation via the IGF‐1 receptor. H7, a nonspecific inhibitor of serine‐threonine kinase, inhibited IGF‐1‐dependent stimulation of AIB uptake. In addition, calphostin C (a specific inhibitor of protein kinase C), but not H89 (a specific inhibitor of protein kinase A), inhibited the IGF‐1 action. This study further characterizes regulated amino acid uptake by the human placental trophoblasts and demonstrates that the Na+‐dependent component of AIB uptake is stimulated by physiologic concentrations of IGF‐1. © 1995 Wiley‐Liss Inc.
Insulin‐like growth factors modulate the growth inhibitory effects of retinoic acid on MCF‐7 breast cancer cells
Authors: Bentel Jacqueline M. , Lebwohl David E. , Cullen Kevin J. , Rubin Mark S. , Rosen Neal , Mendelsohn John , Miller Wilson H. 
Published: February 2005

AbstractRetinoids are currently being tested for the treatment and prevention of several human cancers, including breast cancer. However, the anti‐cancer and growth inhibitory mechanisms of retinoids are not well understood. All‐trans retinoic acid (RA) inhibits the growth of the estrogen receptor‐positive (ER+) breast cancer cell line, MCF‐7, in a reversible and dose‐dependent manner. In contrast, insulin‐like growth factors (IGF‐I,IGF‐II) and insulin are potent stimulators of the proliferation of MCF‐7 and several other breast cancer cell lines. Pharmacologic doses of RA (≤10−6M) completely inhibit IGF‐I‐stimulated MCF‐7 cell growth. Published data suggest that the growth inhibitory action of RA on IGF‐stimulated cell growth is linear and dose‐dependent, similar to RA inhibition of unstimulated or estradiol‐stimulated MCF‐7 cell growth. Surprisingly, we have found that IGF‐I or insulin‐stimulated cell growth is increased to a maximum of 132% and 127%, respectively, by cotreatment with 10−7 M RA, and that 10−9–10−7 M RA increase cell proliferation compared to IGF‐I or insulin alone. MCF‐7 cells that stably overexpress IGF‐II are also resistant to the growth inhibitory effects of 10−9–10−7 M RA. Treatment with the IGF‐I receptor blocking antibody, αIR‐3, restores RA‐induced growth inhibition of IGF‐I‐treated or IGF‐II‐overexpressing MCF‐7 cells, indicating that the IGF‐I receptor is mediating these effects. IGFs cannot reverse all RA effects since the altered cell culture morphology of RA‐treated cells is similar in growth‐inhibited cultures and in IGF‐II expressing clones that are resistant to RA‐induced growth inhibition. These results indicate that RA action on MCF‐7 cells is biphasic in the presence of IGF‐I or insulin with 10−9–10−7 M RA enhancing cell proliferation and ≥ 10−6M RA causing growth inhibition. As IGF‐I and IGF‐II ligands are frequently detectable in breast tumor tissues, their potential for modulation of RA effects should be considered when evaluating retinoids for use in in vivo experimental studies and for clinical purposes. Additionally, the therapeutic use of inhibitors of IGF action in combination with RA is suggested by these studies. © 1995 Wiley‐Liss Inc.
Cytokines and growth factors modulate cell growth and insulin‐like growth factor binding protein secretion by the human salivary cell line (HSG)
Authors: Katz Joseph , Weiss Hana , Goldman Boleslaw , Kanety Hana , Stannard Bethel , Leroith Derek , Shemer Joshua 
Published: February 2005

AbstractThe human salivary cell line (HSG) was investigated for the effect of various growth factors and cytokines on cellular proliferation and on the production of insulin‐like growth factor binding proteins (IGFBPs). IGF‐l increased cell growth by approximately 25%, and induced the appearances of three distinct protein bands on ligand blot of the cell culture. Two bands with molecular weights of 43 and 45. Kda, respectively, proved to be IGFBP‐3 using a specific antibody, and the third was a 24 Kda species (probably, IGFBP‐4). Similar IGFBPs were released by the cells following stimulation by EGF and insulin as well as following incubation with the IGF‐I receptor antibody αIR3. Retinoic acid had an inhibitory effect (50%) on IGF‐I‐induced cellular proliferation and an attenuative effect on the 24 Kda band when it was combined with IGF‐I, and to a lesser effect EGF; however, it enhanced IGFBP‐3 production when incubated with IGF‐I. The IGF‐I receptor antibody had an agonistic effect on IGFBPs production when applied alone or together with IGF‐I. TNF‐α and INF‐γ had minimal effects on cell growth when added alone but when applied in combination, a marked inhibition of cellular proliferation was noted. These cytokines caused increased accumulation of IGFBP‐3, −4, and −5. Addition of IGF‐I to these cytokines enhanced the expression of these bands. These data demonstrate that growth factors and cytokines which modulate HSG cell growth, induce specific IGFBPs which may play a role in their effects on cell growth. © 1995 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.
Differential regulation of the synthesis and activity of the major cyclin‐dependent kinases, p34cdc2, p33cdk2, and p34cdk4, during cell cycle entry and progression in normal human T lymphocytes
Authors: Lucas Joseph J. , Szepesi Agota , Domenico Joanne , Tordai Attila , Terada Naohiro , Gelfand Erwin W. 
Published: February 2005

AbstractThree major cyclin‐dependent kinases, p34cdc2, p33cdk2, and p34cdk4 were examined in normal human T cells stimulated to enter the cell cycle in vitro. None of the three genes was expressed in resting T cells. Transcripts from the cdk4 and cdk2 genes were detectable as early as 3 and 8 hr after stimulation, respectively, whereas cdc2 gene transcripts were not detectable until about 24 hr, shortly before S phase entry. Immunoblot analysis showed that resting T cells contained little p34cdk4, no p34cdc2, and a low level of p33cdk2 protein. Increased amounts of p34cdk4, p33cdk2, and p34cdc2 proteins were seen at about 7, 10, and 30 hr after stimulation, respectively. Immunoprecipitates of each of the kinases were assessed for histone H1 kinase activity. Activity due to p33cdk2 first became detectable in mid‐G1 phase and increased dramatically after entry into S phase. Active p34cdc2 kinase was not detected until about 40 hr after stimulation, about 10 hr after the first appearance of the protein. Immunoprecipitates of p34cdk4 possessed almost no H1 histone kinase activity; however, activity was detected as early as 10 hr after cell activation when a protein (p60Rb) derived from the retinoblastoma susceptibility gene product was used as substrate. Cells were synchronized about the G1/S and G2/M borders by aphidicolin and nocodazole. Cells arrested prior to S‐phase contained high levels of active p33cdk2 and essentially no active p34cdc2, despite the fact that large amounts of both proteins were present. Cells arrested by nocodazole had high levels of active p34cdc2 and greatly reduced levels of p33cdk2 kinase activity. The results suggest that the major role for the p34cdc2 kinase is at mitosis, whereas that for p33cdk2 is in late G1 and/or S phase. The p34cdk4 protein, present in aphidicolin‐blocked cells, was nearly absent from cells arrested at the G2/M border; however, kinase activity was low in cells blocked at both points, suggesting that the major role for p34cdk4 may be in G1 phase. © 1995 Wiley‐Liss, Inc.
Copper‐mediated intra‐ligand oxygen transfer in gas‐phase complexes with 3‐nitrotyrosine
Authors: Vaisar Tomáš , Heinecke Jay W. , Seymour Jennifer L. , Tureček František 
Published: February 2005

AbstractGas‐phase ternary complexes with Cu(II) and 2,2′‐bipyridine (bpy) of tyrosine, 3‐aminotyrosine, 3‐nitrotyrosine and 3‐nitrotyrosine methyl ether are formed readily upon electrospraying aqueous methanol solutions containing the components. In contrast to Cu(bpy) complexes of tyrosine, 3‐aminotyrosine and other aromatic amino acids, the complexes of 3‐nitrotyrosine and its methyl ether undergo unusual collisionally activated dissociations (CADs) that involve Cu‐mediated transfer of an oxygen atom from the nitro group. With 3‐nitrotyrosine this results in an expulsion of carbonic acid, H2CO3, whereas with 3‐nitrotyrosine methyl ether an OH migration forms Cu(OH)bpy+ as the predominant product. To the best of our knowledge, this is the first case of an intra‐ligand redox reaction in a gas‐phase organometallic complex. The reaction mechanism of this unusual dissociation was elucidated by a combination of isotope labeling, accurate mass measurements, energy‐resolved CAD mass spectra and density functional theory calculations of ion structures and relative energies. Copyright © 2005 John Wiley & Sons, Ltd.
Incorporating uncertainty in the PROMETHEE MCDA method
Authors: Hyde Kylie , Maier Holger R. , Colby Christopher 
Published: February 2005

AbstractAnalyses of complex decision‐making problems, involving tradeoffs among multiple criteria, is often undertaken using the PROMETHEE multi‐criteria decision analysis (MCDA) outranking technique. Various sources of uncertainty exist in the application of MCDA methods including the definition of criteria weights and the assignment of criteria performance values. Generalized criterion functions were incorporated in PROMETHEE to take the uncertainty in the criteria performance values into account; however, actors find it extremely difficult to select the generalized criterion functions and their associated thresholds for each criterion, which therefore results in an additional source of uncertainty. Furthermore, the generalized criterion functions do not address the subjectivity and uncertainty in the criteria weights, therefore, this form of uncertainty is usually assessed by sensitivity analysis methods. In this paper, a reliability‐based approach is proposed which enables the decision maker to examine the robustness of the solution obtained from PROMETHEE. The proposed approach therefore allows a decision to be made with confidence that the alternative chosen is the best performing alternative under the range of probable circumstances, without being required to define the generalized criterion functions. The proposed stochastic method involves defining the uncertainty in the input values using probability distributions, performing a reliability analysis by Monte Carlo simulation and undertaking a significance analysis using the Spearman rank correlation coefficient. The outcomes of the approach include a distribution of the total flows of each alternative based upon the expected range of input parameter values. The benefits of the approach are illustrated by applying it to a renewable energy case study. Copyright © 2005 John Wiley & Sons, Ltd.