bluuebunny/crossref_metadata_2025_split huggingface dataset:
G1 tetraploidy checkpoint and the suppression of tumorigenesis
Authors: Margolis Robert L. , Lohez Olivier D. , Andreassen Paul R. 
Published: February 2003

AbstractCheckpoints suppress improper cell cycle progression to ensure that cells maintain the integrity of their genome. During mitosis, a metaphase checkpoint requires the integration of all chromosomes into a metaphase array in the mitotic spindle prior to mitotic exit. Still, mitotic errors occur in mammalian cells with a relatively high frequency. Metaphase represents the last point of control in mitosis. Once the cell commits to anaphase there are no checkpoints to sense segregation defects. In this context, we will explore our recent finding that non‐transformed mammalian cells have a checkpoint that acts subsequent to mitotic errors to block the proliferation of cells that have entered G1 with tetraploid status. This arrest is dependent upon both p53 and pRb, and may represent an important function of both p53 and pRb as tumor suppressors. Further, we discuss the possibility that this mechanism may similarly impose G1 arrest in cells that become aneuploid through errors in mitosis. © 2002 Wiley‐Liss, Inc.
Role of testicular interstitial macrophages in regulating testosterone release in hyperprolactinemia
Authors: Huang William J. , Yeh Jiun‐Yih , Kan Shu‐Fen , Chang Luke S. , Wang Paulus S. 
Published: February 2003

AbstractHyperprolactinemia‐induced hypogonadism has been linked to a dysfunction of the hypothalamus‐pituitary‐testis axis. The direct inhibitory effects of prolactin on the testicular release of testosterone have also been demonstrated, though their mechanisms remain unclear. Incubation of rat testicular interstitial cells (TICs) with prolactin stimulated the release of testosterone. TICs from rats with anterior pituitary‐grafting‐induced hyperprolactinemia release lower amounts of testosterone than controls. However, Leydig cells isolated from anterior pituitary‐grafted rats release a greater amount of testosterone. These paradoxical observations have remained unexplained. This study examined the roles of testicular interstitial macrophages and of their product, tumor necrosis factor‐α (TNF‐α), in regulating Leydig cells under condition of hyperprolactinemia. Hyperprolactinemia was induced by grafting two anterior pituitary glands of rats under the renal capsule. Control animals were grafted with rat cortex tissue. The rats were sacrificed 6 weeks later. TICs and macrophages, and Leydig cells were isolated for in vitro incubation and drugs challenge. Testosterone released by testicular interstitial or Leydig cells was measured by radioimmunoassay. TNF‐α concentration in the medium of TICs or macrophages was measured by enzyme‐linked immunosorbent assay (ELISA). A dose‐dependent stimulation of TNF‐α secretion in the medium of TICs or macrophages by the prolactin challenge was observed. Higher amounts of TNF‐α were released by TICs in the anterior pituitary‐grafted rats than in the control group. In contrast, the release of TNF‐α by testicular interstitial macrophages isolated from the anterior pituitary‐ and cortex‐grafted groups was quantitatively similar. Challenge with human chorionic gonadotropin did not modify the TNF‐α release by testicular interstitial macrophages in either group. Challenge of Leydig cells with TNF‐α inhibited their release of testosterone stimulated by human chorionic gonadotropin, but not their basal testosterone release. These different patterns of testosterone release in TICs versus Leydig cells cultures in anterior pituitary‐grafted rats may be due to the influence of testicular interstitial macrophages. These observations correlate with in vivo conditions, where prolactin increases the release of TNF‐α by testicular interstitial macrophages, which, in turn, decreases the human chorionic gonadotropin‐stimulated release of testosterone by Leydig cells. In summary, hyperprolactinemia‐induced hypogonadism involves a mechanism of prolactin‐originated, macrophage‐mediated inhibitory regulation of testosterone release by Leydig cells. TNF‐α, one of the cytokines secreted by macrophages, may play a key role in this mechanism. © 2002 Wiley‐Liss, Inc.
Lysyl oxidase: Properties, specificity, and biological roles inside and outside of the cell
Authors: Kagan Herbert M. , Li Wande 
Published: February 2003

AbstractLysyl oxidase (LO) plays a critical role in the formation and repair of the extracellular matrix (ECM) by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent crosslinkages which stabilize these fibrous proteins. Its catalytic activity depends upon both its copper cofactor and a unique carbonyl cofactor and has been shown to extend to a variety of basic globular proteins, including histone H1. Although the three‐dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis‐suppressing function of the propeptide domain of prolysyl oxidase. Recent studies have demonstrated that LO appears to function within the cell in a manner, which strongly modifies cellular activity. Newly discovered LO‐like proteins also likely play unique roles in biology. © 2002 Wiley‐Liss, Inc.
Conservative segregation of maternally inherited CS histone variants in larval stages of sea urchin development
Authors: Oliver María Isabel , Rodríguez Carla , Bustos Paula , Morín Violeta , Gutierrez Soraya , Montecino Martín , Genevière Anne Marie , Puchi Marcia , Imschenetzky María 
Published: February 2003

AbstractThree sets of histone variants are coexisting in the embryo at larval stages of sea urchin's development: the maternally inherited cleavage stage variants (CS) expressed during the two initial cleavage divisions, the early histone variants, which are recruited into embryonic chromatin from middle cleavage stages until hatching and the late variants, that are fundamentally expressed from blastula stage onward. Since the expression of the CS histones is confined to the initial cleavage stages, these variants represent a very minor proportion of the histones present in the plutei larvae, whereas the late histone variants are predominant. To determine the position of these CS in the embryonic territories, we have immunolocalized the CS histone variants in plutei larvas harvested 72 h post‐fertilization. In parallel, we have pulse labeled the DNA replicated during the initial cleavage cycle with bromodeoxyuridine (BrdU) and its position was further determined in the plutei larvas by immunofluorescence. We have found that the CS histone variants were segregated to specific territories in the plutei. The position in which the CS histone variants were found to be segregated was consistent with the position in which the DNA molecules that were replicated during the initial cleavage divisions were localized. These results strongly suggest that a specification of embryonic nuclei occurs at the initial cleavage divisions which is determined by a chromatin organized by CS histone variants. © 2002 Wiley‐Liss, Inc.
New insights into the mechanisms of vitamin D action
Authors: Christakos Sylvia , Dhawan Puneet , Liu Yan , Peng Xiaorong , Porta Angela 
Published: February 2003

AbstractThe biologically active metabolite of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) is a secosteroid whose genomic mechanism of action is similar to that of other steroid hormones and is mediated by stereospecific interaction of 1,25(OH)2D3 with the vitamin D receptor (VDR) which heterodimerizes with the retinoid X receptor (RXR). After interaction with the vitamin D response element (VDRE) in the promoter of target genes, transcription proceeds through the interaction of VDR with coactivators and with the transcription machinery. The identification of the steps involved in this process has been a major focus of recent research in the field. However, the functional significance of target proteins as well as the functional significance of proteins involved in the transport and metabolism of vitamin D is also of major importance. Within the past few years much new information has been obtained from studies using knockout and transgenic mice. New insight has been obtained using this technology related to the physiological significance of the vitamin D binding protein (DBP), used to transport vitamin D metabolites, as well as the physiological significance of target proteins including 25‐hydroxyvitamin D3 24‐hydroxylase (24(OH)ase), 25‐hydroxyvitamin D3‐1α‐hydroxylase (1α‐(OH)ase), VDR, and osteopontin. The crystal structure of the DBP and the ligand binding domain of the VDR have recently been reported, explaining, in part, the unique properties of these proteins. In addition novel 1,25(OH)2D3 target genes have been identified including the epithelial calcium channel, present in the proximal intestine and in the distal nephron. Thus in recent years a number of exciting discoveries have been made that have enhanced our understanding of mechanisms involved in the pleiotropic actions of 1,25(OH)2D3. © 2002 Wiley‐Liss, Inc.
SPARC regulates cell cycle progression in mesangial cells via its inhibition of IGF‐dependent signaling
Authors: Francki Aleksandar , Motamed Kouros , McClure Timothy D. , Kaya Marcus , Murri Carrie , Blake David J. , Carbon Juliet G. , Sage E. Helene 
Published: February 2003

AbstractGlomerular mesangial cells both synthesize and respond to insulin‐like growth factor‐1 (IGF‐1). Increased activity of the IGF signaling pathway has been implicated as a major contributor to renal enlargement and subsequent development of diabetic nephropathy. Secreted protein acidic and rich in cysteine (SPARC), a matricellular protein, has been shown to modulate the interaction of cells with growth factors and extracellular matrix. We have reported that primary glomerular mesangial cells derived from SPARC‐null mice exhibit an accelerated rate of proliferation and produce substantially decreased levels of transforming growth factor β1 (TGF‐β1) in comparison to their wild‐type counterparts (Francki et al. [1999] J. Biol. Chem. 274: 32145–32152). Herein we present evidence that SPARC modulates IGF‐dependent signaling in glomerular mesangial cells. SPARC‐null mesangial cells produce increased amounts of IGF‐1 and ‐2, as well as IGF‐1 receptor (IGF‐1R) in comparison to wild‐type cells. Addition of recombinant SPARC to SPARC‐null cells inhibited IGF‐1‐stimulated mitogen activated protein kinase (MAPK) activation and DNA synthesis. We also show that the observed accelerated rate of basal and IGF‐1‐stimulated proliferation in mesangial cells derived from SPARC‐null animals is due, at least in part, to markedly diminished levels of cyclin D1 and the cyclin‐dependent kinase (cdk) inhibitors p21 and p27. Since expression of SPARC in the glomerulus is especially prominent during renal injury, our findings substantiate previous claims that SPARC is involved in glomerular remodeling and repair, a process commonly associated with mesangioproliferative glomerulonephritis and diabetic nephropathy. © 2003 Wiley‐Liss, Inc.
Differential roles of hydrogen peroxide and superoxide in mediating IL‐1‐induced NF‐κB activation and iNOS expression in bovine articular chondrocytes
Authors: Mendes Alexandrina Ferreira , Caramona M. Margarida , Carvalho A. Pato , Lopes M. Celeste 
Published: February 2003

AbstractOur previous studies showed that reactive oxygen species (ROS) are required for the pro‐inflammatory cytokine interleukin‐1β (IL‐1) to induce the activity of the Nuclear transcription Factor‐kappaB (NF‐κB) and the expression of the inducible isoform of the nitric oxide synthase (iNOS) in bovine articular chondrocytes. This study aimed at elucidating the role of hydrogen peroxide (H2O2) and the superoxide radical, two major ROS, in mediating those IL‐1‐induced responses. The results obtained show that chondrocytes produce both H2O2 and superoxide radical in response to IL‐1. Treatment of the chondrocyte cultures with H2O2 alone did not induce NF‐κB activation or iNOS expression. Addition of H2O2 simultaneously with IL‐1 did neither enhance nor inhibit NF‐κB activation and iNOS expression, relatively to treatment with IL‐1 alone. Accordingly, treatment with catalase did not inhibit those IL‐1‐induced responses. Treatment with superoxide dismutase, however, effectively prevented IL‐1‐induced IκB‐α degradation and iNOS expression. Taken together, the results obtained indicate that superoxide mediates IL‐1‐induced IκB‐α degradation and the consequent NF‐κB activation and iNOS expression in chondrocytes, whereas H2O2 does not seem to participate in those IL‐1‐induced responses. In conclusion, the present study identifies the superoxide radical as the ROS involved in mediating the IL‐1‐induced signaling pathway that leads to NF‐κB activation and to the expression of NF‐κB‐dependent genes in bovine articular chondrocytes. © 2003 Wiley‐Liss, Inc.
Expression of interleukin‐1β and interleukin‐1 receptor antagonist in oxLDL‐treated human aortic smooth muscle cells and in the neointima of cholesterol‐fed endothelia‐denuded rabbits
Authors: Lin Shing‐Jong , Yen Hui‐Tzu , Chen Yung‐Hsiang , Ku Hung‐Hai , Lin Feng‐Yen , Chen Yuh‐Lien 
Published: February 2003

AbstractThe migration of vascular smooth muscle cells (VSMCs) from the media to the intima and the proliferation of intimal VSMCs are key events in restenotic lesion development. These events, which are preceded and accompanied by inflammation, are modulated by the proinflammatory cytokine, interleukin‐1β (IL‐1β), which induces vascular smooth muscle cells to express adhesion molecules and to proliferate. IL‐1β action is complex and regulated, in part, by its naturally occurring inhibitor, the IL‐1 receptor antagonist (IL‐1ra). Whether there was a temporal and spatial correlation between IL‐1β and IL‐1ra expression in, and release by, oxidized low density lipoproteins (oxLDL)‐stimulated human aortic smooth muscle cells (HASMCs) was determined by using ELISA and Western blot. In addition, IL‐1β and IL‐1ra expression was detected in the neointima of endothelia‐denuded cholesterol‐fed New Zealand white rabbits by immunohistochemistry and Western blot. In HASMCs, oxLDL induced IL‐β and IL‐1ra expression and release in a dose‐ and time‐dependent manner. Treatment with 20 μg/ml oxLDL resulted in increased IL‐1β release after 6 h, which peaked at 24 h, and in increased IL‐1ra release, first seen after 12 h, but continuing to increase for at least 48 h. In the cells, IL‐β expression showed a similar pattern to release, whereas IL‐1ra expression was seen in unstimulated cells and was not increased by oxLDL treatment. Confocal microscopy showed colocalization of IL‐β and IL‐1ra expression in oxLDL‐stimulated HASMCs. oxLDL caused significant induction of nuclear factor kappa B and activator protein‐1 DNA binding activity in HASMCs (6.6‐ and 3.3‐fold, respectively). In cholesterol‐fed endothelia‐denuded rabbits, the notably thickened intima showed significant IL‐1β and IL‐1ra expression. These results provide further support for the role of IL‐1 system in the pathogenesis of restenosis. This is the first demonstration of IL‐1β and IL‐1ra expression and secretion of oxLDL‐treated HASMCs and their expression in the rabbit neointima, suggesting that the smooth muscle cells of the intima are an important source of these factors. © 2003 Wiley‐Liss, Inc.
Vitamin D receptor is not required for the rapid actions of 1,25‐dihydroxyvitamin D3 to increase intracellular calcium and activate protein kinase C in mouse osteoblasts
Authors: Wali Ramesh K. , Kong Juan , Sitrin Michael D. , Bissonnette Marc , Li Yan Chun 
Published: February 2003

AbstractThe rapid, non‐genomic actions of 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] have been well described, however, the role of the nuclear vitamin D receptor (VDR) in this pathway remains unclear. To address this question, we used VDR(+/+) and VDR(−/−) osteoblasts isolated from wild‐type and VDR null mice to study the increase in intracellular calcium ([Ca2+]i) and activation of protein kinase C (PKC) induced by 1,25(OH)2D3. Within 1 min of 1,25(OH)2D3 (100 nM) treatment, an increase of 58 and 53 nM in [Ca2+]i (n = 3) was detected in VDR(+/+) and VDR(−/−) cells, respectively. By 5 min, 1,25(OH)2D3 caused a 2.1‐ and 1.9‐fold increase (n = 6) in the phosphorylation of PKC substrate peptide acetylated‐MBP4–14 in VDR(+/+) and VDR(−/−) osteoblasts. The 1,25(OH)2D3‐induced phosphorylation was abolished by GF109203X, a general PKC inhibitor, in both cell types, confirming that the secosteroid induced PKC activity. Moreover, 1,25(OH)2D3 treatment resulted in the same degree of translocation of PKC‐α and PKC‐δ, but not of PKC‐ζ, from cytosol to plasma membrane in both VDR(+/+) and VDR(−/−) cells. These experiments demonstrate that the 1,25(OH)2D3‐induced rapid increases in [Ca2+]i and PKC activity are neither mediated by, nor dependent upon, a functional nuclear VDR in mouse osteoblasts. Thus, VDR is not essential for these rapid actions of 1,25(OH)2D3 in osteoblasts. © 2003 Wiley‐Liss, Inc.
Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts
Authors: Rifas Leonard , Arackal Sophia , Weitzmann M. Neale 
Published: February 2003

AbstractActivated T cells secrete multiple osteoclastogenic cytokines which play a major role in the bone destruction associated with rheumatoid arthritis. While the role of T cells in osteoclastogenesis has received much attention recently, the effect of T cells on osteoblast formation and activity is poorly defined. In this study, we investigated the hypothesis that in chronic inflammation activated T cells contribute to enhanced bone turnover by promoting osteoblastic differentiation. We show that T cells produce soluble factors that induce alkaline phosphatase activity in bone marrow stromal cells and elevated expression of mRNA for Runx2 and osteocalcin. This data indicate that T cell derived factors have the capacity to stimulate the differentiation of bone marrow stromal cells into the osteoblast phenotype. RANKL mRNA was undetectable under any conditions in highly purified bone marrow stromal cells. In contrast, RANKL was constitutively expressed in primary osteoblasts and only moderately up‐regulated by activated T cell conditioned medium. Interestingly, both bone marrow stromal cells and osteoblasts expressed mRNA for RANK, which was strongly up‐regulated in both cell types by activated T cell conditioned medium. Although, mRNA for the RANKL decoy receptor, osteoprotegerin, was also up‐regulated by activated T cell conditioned medium, it's inhibitory effects may be mitigated by a simultaneous rise in the osteoprotegerin competitor TNF‐related apoptosis‐inducing ligand. Based on our data we propose that during chronic inflammation, T cells regulate bone loss by a dual mechanism involving both direct stimulation of osteoclastogenesis, by production of osteoclastogenic cytokines, and indirectly by induction of osteoblast differentiation and up‐regulation of bone turnover via coupling. J. Cell. Biochem. 88: 650–659, 2003. © 2003 Wiley‐Liss, Inc.
Cell cycle dependent regulation of protein kinase CK2 signaling to the nuclear matrix
Authors: Wang Huamin , Yu Shihui , Davis Alan T. , Ahmed Khalil 
Published: February 2003

AbstractProtein kinase CK2 is a ubiquitous protein serine/threonine kinase that is involved in cell growth and proliferation as well as suppression of apoptosis. Several studies have suggested that the kinase plays a role in cell cycle progression; however, changes in enzyme activity during phases of cell cycle have not been detected. Nuclear matrix is a key locus for CK2 signaling in the nucleus. We therefore examined CK2 signaling to the nuclear matrix in distinct phases of cell cycle by employing synchronized ALVA‐41 prostate cancer cells. Removal of serum from the culture medium resulted in G0/G1 arrest, and a reduction in the nuclear matrix‐associated CK2 activity which was rapidly reversed on addition of serum. Arresting the cells in G0/G1 phase with hydroxyurea and subsequent release to S phase by serum gave similar results. Cells arrested in the G2/M phase by treatment with nocodazole demonstrated an extensive reduction in the nuclear matrix‐associated CK2 which was reversed rapidly on addition of serum. Changes in the immunoreactive CK2 protein were concordant with the activity data reflecting a dynamic trafficking of the kinase in distinct phases of cell cycle. Under the same conditions, CK2 activity in total cellular lysate remained essentially unaltered. These results provide the first direct evidence of discrete modulations of CK2 in the nuclear matrix during the cell cycle progression. Inducible overexpression of CK2 in CHO cells yielded only a modest increase in CK2 activity even though a significant increase in expression was apparent at the level of CK2α‐specific message. Stably transfected ALVA‐41 cells, however, did not show a significant change in CK2 levels despite increased expression at the message level. Not surprisingly, both types of the stably transfected cells failed to show any alteration in cell cycle progression. Distribution of the CK2 activity in the cytosolic versus nuclear matrix fractions in normal cells appears to be different from that in the cancer cells such that the ratio of nuclear matrix to cytosolic activity is much higher in the latter. Considering that nuclear matrix is central to several nuclear functions, this pattern of intracellular distribution of CK2 may have implications for its role in the oncogenic process. Published 2003 Wiley‐Liss, Inc.
The use of strategic tools by small and medium‐sized enterprises: an Australasian study
Authors: Frost Frederick A. 
Published: February 2003

Abstract
This paper reviews the range of strategic tools and techniques available to strategic planners.
The study focuses on strategic planning tool usage by small and medium‐sized enterprises (SMEs) in Western Australia, Singapore, Hong Kong and Malaysia.
A six‐stage strategic framework was used to provide for 36 core strategic tasks.
Results are contrasted with a previous study published in this journal that considered the use of strategic tools by organizations in the United Kingdom and New Zealand.
SMEs were found to use a restricted range of strategic tools. There is a need for a wider understanding of the tools available and their application to strategy development.
Copyright © 2003 John Wiley & Sons, Ltd.
Outsourcing: the supplier viewpoint
Authors: Hussey David , Jenster Per 
Published: February 2003

Abstract
Outsourcing, which is the process of shifting tasks and services previously performed in‐house to outside vendors, is hardly a new idea in management. But the volume, extent and character of outsourcing has been changing rapidly.
Outsourcing is now a fashionable activity and has become a management fad as much as a reasoned decision. It can offer great opportunities to both the buyer and supplier when used wisely. When it becomes a mantra and used without thought, it can do great damage to both parties.
Copyright © 2003 John Wiley & Sons, Ltd.