bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Inhibition of RANKL Causes Greater Suppression of Bone Resorption and Hypercalcemia Compared with Bisphosphonates in Two Models of Humoral Hypercalcemia of Malignancy
Authors: Morony Sean , Warmington Kelly , Adamu Stephen , Asuncion Frank , Geng Zhaopo , Grisanti Mario , Tan Hong Lin , Capparelli Casey , Starnes Charlie , Weimann Bernadette , Dunstan Colin R. , Kostenuik Paul J. 
Published: April 2005

Abstract
Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone by inducing the expression of receptor activator for nuclear factor-κB ligand (RANKL), a protein that is essential for osteoclast formation, activation, and survival. RANKL does not influence renal calcium reabsorption, so RANKL inhibition is a rational approach to selectively block, and thereby reveal, the relative contribution of bone calcium to HHM. We used the RANKL inhibitor osteoprotegerin (OPG) to evaluate the role of osteoclast-mediated hypercalcemia in two murine models of HHM. Hypercalcemia was induced either by sc inoculation of syngeneic colon (C-26) adenocarcinoma cells or by sc injection of high-dose recombinant PTHrP (0.5 mg/kg, sc, twice per day). In both models, OPG (0.2–5 mg/kg) caused rapid reversal of established hypercalcemia, and the speed and duration of hypercalcemia suppression were significantly greater with OPG (5 mg/kg) than with high-dose bisphosphonates (pamidronate or zoledronic acid, 5 mg/kg). OPG also caused greater reductions in osteoclast surface and biochemical markers of bone resorption compared with either bisphosphonate. In both models, hypercalcemia gradually returned despite clear evidence of ongoing suppression of bone resorption by OPG. These data demonstrate that osteoclasts and RANKL are important mediators of HHM, particularly in the early stages of the condition. Aggressive antiresorptive therapy with a RANKL inhibitor therefore might be a rational approach to controlling HHM.
Proliferation of Endothelial and Tumor Epithelial Cells by Progestin-Induced Vascular Endothelial Growth Factor from Human Breast Cancer Cells: Paracrine and Autocrine Effects
Authors: Liang Yayun , Hyder Salman M. 
Published: April 2005

Abstract
Angiogenesis, the formation of new blood vessels, is essential for tumor expansion, and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic growth factors known. We have previously shown that natural and synthetic progestins, including those used in hormone replacement therapy and oral contraception, induce the synthesis and secretion of VEGF in a subset of human breast cancer cells in a progesterone receptor-dependent manner. We now report that conditioned medium from progestin-treated breast tumor cells can induce the proliferation of endothelial cells in a paracrine manner and induce the proliferation of tumor epithelial cells in a paracrine and an autocrine manner. The use of an anti-VEGF antibody and SU-1498, an inhibitor of VEGF receptor-2 (VEGFR-2 or flk/kdr) tyrosine kinase activity, demonstrated that these effects involve interactions between VEGF and VEGFR-2. Also, blockage of progestin-induced VEGF by the antiprogestin RU-486 (mifepristone) eliminated VEGF-induced proliferative effects. The ability of VEGF to increase the proliferation of endothelial cells and tumor cells, including those that do not release VEGF in response to progestins, suggests that these effects are mediated by amplification of the progestin signal, which culminates in angiogenesis and tumor growth. These novel findings suggest that targeting the release of VEGF from tumor epithelial cells as well as blocking interactions between VEGF and VEGFR-2 on both endothelial and tumor epithelial cells may facilitate the development of new antiangiogenic therapies for progestin-dependent breast tumors. Furthermore, these data indicate that it would be useful to develop selective progesterone receptor modulators that prevent the release of angiogenic growth factors from breast cancer cells.
Insulin-Like Growth Factor (IGF)-I Stimulates Cell Proliferation and Induces IGF Binding Protein (IGFBP)-3 and IGFBP-5 Gene Expression in Cultured Growth Plate Chondrocytes via Distinct Signaling Pathways
Authors: Kiepe Daniela , Ciarmatori Sonia , Hoeflich Andreas , Wolf Eckhard , Tönshoff Burkhard 
Published: April 2005

AbstractThe bioactivity of IGF-I in the cellular microenvironment is modulated by both inhibitory and stimulatory IGF binding proteins (IGFBPs), whose production is partially under control of IGF-I. However, little is known on the IGF-mediated regulation of these IGFBPs in the growth plate. We therefore studied the effect of IGF-I on IGFBP synthesis and the involved intracellular signaling pathways in two cell culture models of rat growth plate chondrocytes. In growth plate chondrocytes in primary culture, incubation with IGF-I increased the concentrations of IGFBP-3 and IGFBP-5 in conditioned cell culture medium in a dose- and time-dependent manner. Coincubation of IGF-I with specific inhibitors of the p42/44 MAPK pathway (PD098059 or U0126) completely abolished the stimulatory effect of IGF-I on IGFBP-3 mRNA expression but did not affect increased IGFBP-5 mRNA levels. In contrast, inhibition of the phosphatidylinositol-3 kinase signaling pathway by LY294002 abrogated both IGF-I-stimulated IGFBP-3 and -5 mRNA expression. Comparable results regarding IGFBP-5 were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does not express IGFBP-3. The IGF-I-induced IGFBP-5 gene expression required de novo mRNA transcription and de novo protein synthesis. These data suggest that IGF-I modulates its activity in cultured rat growth plate chondrocytes by the synthesis of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins. The finding that IGF-I uses different and only partially overlapping intracellular signaling pathways for the regulation of two IGFBPs with opposing biological functions might be important for the modulation of IGF bioactivity in the cellular microenvironment.
Progesterone Inhibits the Estrogen-Induced Phosphoinositide 3-Kinase→AKT→GSK-3β→Cyclin D1→pRB Pathway to Block Uterine Epithelial Cell Proliferation
Authors: Chen Bo , Pan Haiyan , Zhu Liyin , Deng Yan , Pollard Jeffrey W. 
Published: April 2005

AbstractThe mammalian cell cycle is regulated by the cyclin/cyclin-dependent kinase (CDK) phosphorylation of the retinoblastoma (pRB) family of proteins. Cyclin D1 with its CDK4/6 partners initiates the cell cycle and acts as the link between extracellular signals and the cell cycle machinery. Estradiol-17β (E2) stimulates uterine epithelial cell proliferation, a process that is completely inhibited by pretreatment with progesterone (P4). Previously, we identified cyclin D1 localization as a key point of regulation in these cells with E2 causing its nuclear accumulation and P4 retaining it in the cytoplasm with the resultant inhibition of pRB phosphorylation. Here we show that E2 stimulates phosphoinositide 3-kinase to activate phosphokinase B/AKT to effect an inhibitory phosphorylation of glycogen synthase kinase (GSK-3β). This pathway is suppressed by P4. Inhibition of the GSK-3β activity in P4-treated uteri by the specific inhibitor, LiCl, reversed the nuclear accumulation of cyclin D1 and in doing so, caused pRB phosphorylation and the induction of downstream genes, proliferating cell nuclear antigen and Ki67. Conversely, inhibition of phosphoinositide 3 kinase by LY294002 or Wortmanin reversed the E2-induced GSK-3β Ser9 inhibitory phosphorylation and blocked nuclear accumulation of cyclin D1. These data show the reciprocal actions of E2 and P4 on the phosphoinositide 3-kinase through to the GSK-3β pathway that in turn regulates cyclin D1 localization and cell cycle progression. These data reveal a novel signaling pathway that links E2 and P4 action to growth factor-mediated signaling in the uterus.
An Efficient Improve for the Kröhnke Reaction: One-pot Synthesis of 2,4,6-Triarylpyridines Using Raw Materials under Microwave Irradiation
Authors: Tu Shujiang , Li Tuanjie , Shi Feng , Fang Fang , Zhu Songlei , Wei Xianyong , Zong Zhimin 
Published: April 2005

Abstract
A series of 2,4,6-triarylpyridines have been prepared by the one-pot reaction of aldehydes with aromatic ketones in the presence of ammonium acetate under microwave irradiation without catalyst. This method has the advantage of easier workup, shorter reaction time, higher yield, and environment-friendly.
Standardized Approach to Proteome Profiling of Human Serum Based on Magnetic Bead Separation and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
Authors: Baumann Sven , Ceglarek Uta , Fiedler Georg Martin , Lembcke Jan , Leichtle Alexander , Thiery Joachim 
Published: April 2005

AbstractBackground: Magnetic bead purification for the analysis of low-abundance proteins in body fluids facilitates the identification of potential new biomarkers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The aims of our study were to establish a proteome fractionation technique and to validate a standardized blood sampling, processing, and storage procedure for proteomic pattern analysis.Methods: We used magnetic bead separation for proteome profiling of human blood by MALDI-TOF MS (mass range, 1000–10 000 Da) and studied the effects on the quality and reproducibility of the proteome analysis of anticoagulants, blood clotting, time and temperature of sample storage, and the number of freeze–thaw cycles of samples.Results: The proteome pattern of human serum was characterized by ∼350 signals in the mass range of 1000–10 000 Da. The proteome profile showed time-dependent dynamic changes before and after centrifugation of the blood samples. Serum mass patterns differed between native samples and samples frozen once. The best reproducibility of proteomic patterns was with a single thawing of frozen serum samples.Conclusion: Application of the standardized preanalytical blood sampling and storage procedure in combination with magnetic bead-based fractionation decreases variability of proteome patterns in human serum assessed by MALDI-TOF MS.
In Vivo Characterization of Bone Marrow–Derived Fibroblasts Recruited into Fibrotic Lesions
Authors: Ishii Genichiro , Sangai Takafumi , Sugiyama Kenji , Ito Takashi , Hasebe Takahiro , Endoh Yasushi , Magae Junji , Ochiai Atsushi 
Published: April 2005

Abstract
Fibroblasts, which are widely distributed and play a key part in tissue fibrosis, are phenotypically and functionally heterogeneous. Recent studies reported that bone marrow can be a source of tissue fibroblast. In the study reported here, we investigated in vivo characterization of bone marrow–derived fibroblasts recruited into various fibrotic lesions. Mice were engrafted with bone marrow isolated from transgenic mice expressing green fluorescent protein (GFP), and fibrotic lesions were induced by cancer implantation (skin), excisional wounding (skin), and bleomycin administration (lung). A small population of GFP+ fibroblast was found even in nonfibrotic skin (8.7% ± 4.6%) and lung (8.9% ± 2.5%). The proportion of GFP+ fibroblasts was significantly increased after cancer implantation(59.7%±16.3%) and excisional wounding (32.2% ± 4.8%), whereas it was not elevated after bleomycin administration (7.1% ± 2.4%). Almost all GFP+ fibroblasts in fibrotic lesions expressed type I collagen, suggesting that bone marrow–derived fibroblasts would contribute to tissue fibrosis. GFP+ fibroblasts expressed CD45, Thy-1, and α-smooth muscle actin at various proportions. Our results suggested that bone marrow–derived fibroblasts expressed several fibroblastic markers in vivo and could be efficiently recruited into fibrotic lesions in response to injurious stimuli; however, the degree of recruitment frequency might depend on the tissue microenvironment.
Donor Marker Infidelity in Transgenic Hematopoietic Stem Cells
Authors: Anderson Daniel A. , Wu Yanna , Jiang Shuguang , Zhang Xingqi , Streeter Philip R. , Spangrude Gerald J. , Archer David R. , Fleming William H. 
Published: April 2005

AbstractTransgenic marking approaches are increasingly used to evaluate the developmental potential of stem cells. However, cell fate mapping studies using different transgenic marking systems have produced conflicting results. These disparate findings may be due in part to the infidelity of donor marker gene expression. Analysis of hematopoietic stem cells (c-Kit+, Sca-1+, lineage marker− [KSL]) from a transgenic mouse (1Osb) engineered to ubiquitously express the enhanced green fluorescent protein (EGFP) reveals two distinct populations. Forty percent of KSL cells demonstrate intermediate levels of EGFP fluorescence and differentiate into subpopulations of B cells, T cells, and myeloid cells that do not express EGFP. By contrast, progeny of the remaining 60% of KSL cells are almost exclusively EGFP bright. Long-term multilineage hematopoietic reconstitution and serial transplantation experiments show that these differences in EGFP are a property of self-renewing stem cells. Furthermore, both the transgene integration site and the activation status of a cell are important determinants of EGFP expression. These results indicate that a combination of donor cell markers is required to reliably track the full differentiation potential of transgenic stem cells.
Fluid dynamics in conically tapered microneedles
Authors: Martanto Wijaya , Baisch Stephen M. , Costner Elizabeth A. , Prausnitz Mark R. , Smith Marc K. 
Published: April 2005

AbstractToward achieving painless injections and other microfluidic applications, we microfabricated conically tapered needles of micron dimensions. The relationship between pressure drop and flow rate through microneedles was experimentally quantified as a function of fluid viscosity and microneedle length, diameter, and cone half‐angle. At Reynolds numbers ≲ 100, dimensionless pressure drop (2ΔP/ρv2) sharply decreased with increasing Reynolds number, indicating the importance of viscous forces. At larger Reynolds numbers, the flow was almost inviscid, as indicated by a weak dependency of dimensionless pressure drop on Reynolds number. Numerical simulations showed good agreement with experimental data and predicted that flow through conically tapered microneedles is primarily controlled by the diameter and taper angle at the microneedle tip. A characteristic feature of flow through conically tapered microneedles is a favorable axial pressure gradient that accelerates fluid through the microneedle, thus inhibiting growth of the viscous boundary layer on the microneedle wall. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Modeling of multitype particle flow using the kinetic theory approach
Authors: Iddir Hadjira , Arastoopour Hamid 
Published: April 2005

AbstractThe effects of particle size and/or density on particle interaction and overall behavior of granular flow were studied using the kinetic theory approach. The kinetic theory for granular flow was extended to mixtures of multitype particles assuming a non‐Maxwellian velocity distribution and energy non‐equipartition. Each type of particles was considered as a separate phase with different velocity and granular temperature. The resulting momentum equation for each particulate phase includes phase interaction arising from collisional pressure and particle–particle drag force. When applied to simple shear granular flow of a binary mixture, this model predicts well the energy non‐equipartition and the stresses of particulate systems with different sizes and densities. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Fault‐tolerant control of process systems using communication networks
Authors: El‐Farra Nael H. , Gani Adiwinata , Christofides Panagiotis D. 
Published: April 2005

AbstractA methodology for the design of fault‐tolerant control systems for chemical plants with distributed interconnected processing units is presented. Bringing together tools from Lyapunov‐based nonlinear control and hybrid systems theory, the approach is based on a hierarchical architecture that integrates lower‐level feedback control of the individual units with upper‐level logic‐based supervisory control over communication networks. The local control system for each unit consists of a family of control configurations for each of which a stabilizing feedback controller is designed and the stability region is explicitly characterized. The actuators and sensors of each configuration are connected, via a local communication network, to a local supervisor that orchestrates switching between the constituent configurations, on the basis of the stability regions, in the event of failures. The local supervisors communicate, through a plant‐wide communication network, with a plant supervisor responsible for monitoring the different units and coordinating their responses in a way that minimizes the propagation of failure effects. The communication logic is designed to ensure efficient transmission of information between units, while also respecting the inherent limitations in network resources by minimizing unnecessary network usage and accounting explicitly for the effects of possible delays due to fault‐detection, control computations, network communication and actuator activation. The proposed approach provides explicit guidelines for managing the various interplays between the coupled tasks of feedback control, fault‐tolerance and communication. The efficacy of the proposed approach is demonstrated through chemical process examples. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile
Authors: López‐Camelo Jorge S. , Orioli Iêda M. , Dutra Maria da Graça , Nazer‐Herrera Julio , Rivera Nelson , Ojeda María Elena , Canessa Aurora , Wettig Elisabeth , Fontannaz Ana María , Mellado Cecília , Castilla Eduardo E. 
Published: April 2005

AbstractTo verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre‐existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre‐fortification periods (1982–1989 and 1990–2000), and from one fortified period (2001–2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre‐fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre‐fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends. © 2005 Wiley‐Liss, Inc.
Molekulare Organisation und Signaltransduktion an Kontaktstellen zwischen Membranen
Authors: Groves Jay T. 
Published: April 2005

AbstractOberflächen schaffen eine Umgebung, in der zahlreiche Kräfte zusammenwirken und dabei eine Vielzahl komplexer chemischer Prozesse auslösen. Dies gilt vor allem für Zellmembranen, deren Fluidität und Flexibilität eine Antwort auf chemische Wechselwirkungen an der Oberfläche ermöglichen, wie man sie bei anorganischen Materialien in dieser Form nicht findet. Die Bildung räumlicher Proteinmuster an Membranoberflächen im Bereich von Membrankontaktstellen liefert viele Beispiele für solche Phänomene und spielt darüber hinaus eine wichtige Rolle bei der interzellulären Signaltransduktion. Entsprechend interessieren sich sowohl Physikochemiker als auch Zellbiologen für Wechselwirkungen an Membranoberflächen. Aktuelle, fachübergreifende Untersuchungen zur Bildung von Proteinmustern in immunologischen Synapsen und zur Rekonstitution und Manipulation von Membranen unter Verwendung moderner bildgebender Verfahren werden in diesem Aufsatz vorgestellt.
On the design of practicable numerical experiments to investigate stratospheric temperature change
Authors: Hare Sylvia H. E. , Gray L. J. , Lahoz W. A. , O'Neill A. 
Published: April 2005

AbstractForty‐year, time‐varying GCM integrations have been run both with and without coupled chemistry. The results suggest that while computer resources preclude multi‐member ensemble experiments with coupled chemistry models to achieve statistical significance, robust results can be achieved for some atmospheric parameters by running ensemble experiments with imposed ozone changes. Copyright © 2005 Royal Meteorological Society
Monthly forecast and the summer 2003 heat wave over Europe: a case study
Authors: Vitart Frédéric 
Published: April 2005

AbstractA monthly forecasting system has been set up at ECMWF. Probabilistic scores indicate some potentially useful skill for the periods days 12 to 18 and 19 to 32. A case study of the 2003 heat wave over Europe suggests that the model successfully predicted a risk of heat wave higher than in climatology more than 10 days in advance. Copyright © 2005 Royal Meteorological Society
Stereoselective pharmacokinetics of tetrahydropalmatine after oral administration of (−)‐enantiomer and the racemate
Authors: Hong Zhanying , Fan Guorong , Chai Yifeng , Yin Xueping , Wu Yutian 
Published: April 2005

AbstractTetrahydropalmatine (THP) is a biologically active ingredient isolated from a traditional Chinese herb Rhizoma corydalis (yanhusuo). THP is a racemic mixture which contains 50% of the (+) and 50% of (−) enantiomer. The (−) enantiomer accounts for most of the analgesic effects. Plasma concentrations of THP enantiomers were analyzed by chiral high‐performance liquid chromatography (HPLC) on a Chiralcel OJ column with quantification by UV at 230 nm. The method was used to determine the pharmacokinetics of THP enantiomers in rats and dogs after oral administration of rac‐THP or (−)‐THP. The pharmacokinetic profiles of the two enantiomers after dosing with rac‐THP were significantly different both in rats and dogs. The mean Cmax and AUC0–∞ values in rats were 1.93 ± 0.36 μg/ml and 6.65 ± 2.34 μg·h/ml for the (−) enantiomer, and 1.11 ± 0.25 μg/ml and 2.03 ± 0.45 μg·h/ml for the (+) enantiomer. The mean Cmax and AUC0–∞ in dogs were 1.60 ± 0.81 μg/ml and 9.88 ± 2.58 μg·h/ml for the (−) enantiomer, while 0.36 ± 0.21 μg/ml and 1.22 ± 0.40 μg·h/ml for the (+) enantiomer. rac‐THP at 40 mg/kg and (−)‐THP at 20 mg/kg had very similar plasma concentration–time profiles, and Cmax, AUC0–∞, and t1/2 of the (−) enantiomer in both rats and dogs, indicating that the two treatments were equivalent with respect to the pharmacokinetic properties of the (−) enantiomer. Chirality 17:293–296, 2005. © 2005 Wiley‐Liss, Inc.