bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental profile and mechanisms of GABA‐induced calcium signaling in hippocampal astrocytes
Authors: Meier Silke D. , Kafitz Karl W. , Rose Christine R. 
Published: April 2008

AbstractGABA (γ‐aminobutyric acid) is a transmitter with dual action. Whereas it excites neurons during the first week of postnatal development, it represents the major inhibitory transmitter in the mature brain. GABA also activates astrocytes by binding to ionotropic (GABAA) and metabotropic (GABAB) receptors. This results in glial calcium transients which can induce the release of gliotransmitters, rendering GABA an important mediator of neuron‐glia interaction. Using whole‐cell patch‐clamp and ratiometric calcium imaging in hippocampal slices from rats at postnatal days 3–34, we have analyzed the developmental profile as well as the cellular mechanisms of calcium signals induced by GABAA and GABAB receptor activation in astrocytes. We found that GABA‐evoked glial calcium transients are mediated by both GABAA and GABAB receptors. Throughout development, GABAA‐receptor activation resulted in immediate calcium transients in the vast majority of astrocytes, most likely by influx of calcium through voltage‐gated calcium channels. GABAB receptor activation, in contrast, resulted in delayed calcium transients, which were blocked following depletion of intracellular calcium stores and during persistent activation of heterotrimeric G‐proteins. GABAB receptor‐mediated calcium signals exhibited a clear developmental profile with less than 10% of astrocytes responding at P3 or P32–34, and about 60% of cells between P11 and P15. Our data thus indicate that GABAB receptor‐mediated calcium transients are due to calcium release from intracellular stores following G‐protein activation. Moreover, GABAB receptor‐mediated calcium signaling in astrocytes preferentially occurs at a period during postnatal development when hippocampal networks are established. © 2008 Wiley‐Liss, Inc.
Cancer of the tonsil presenting as central nervous system metastasis: A case report
Authors: Dobelbower Michael C. , Nabell Lisle , Markert James , Carroll William , Said‐Al‐Naief Nasser , Meredith Ruby 
Published: April 2008

AbstractBackgroundMetastases from tonsilar cancers are uncommon, usually found in the lung and less commonly in the bone, liver, and mediastinal sites. Only approximately 20% of patients die from distant metastasis. Central nervous system (CNS) metastases usually appear later in the course of the disease, with only 1% to 2% of patients developing metastasis involving the CNS in the course of their disease. Patients seen with symptomatic CNS lesions are rare.Methods and ResultsA case report is presented of a patient seen with signs and symptoms of CNS disease from an isolated CNS metastasis. The primary site was ultimately determined to be of tonsilar origin. The patient's treatment and outcome are discussed.ConclusionsTonsilar cancers seen with signs and symptoms of CNS disease is a rare event. The benefit of aggressive treatment of isolated CNS metastasis from head and neck cancers will likely be gained from case reports because the incidence is quite low. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Comparison of sensory recovery and morphologic change between sensate and nonsensate flaps in oral cavity and oropharyngeal reconstruction
Authors: Kim Jin Hwan , Rho Young Soo , Ahn Hwoe Young , Chung Chul Hoon 
Published: April 2008

AbstractBackgroundSensory recovery after oral cavity and oropharyngeal reconstruction is 1 of the most important goals of free flap reconstruction. The aim of this study was to compare sensory recovery of sensate and nonsensate free flaps and to evaluate the morphologic differences between sensate and nonsensate free flaps.MethodsA total of 27 cases of radial forearm free flap reconstruction after oral cavity and oropharyngeal cancer resection were included in this study. Fifteen flaps were sensate flaps, and the other 12 flaps were nonsensate flaps. The sensory recovery was evaluated in 5 subjective senses: light tough, deep pressure, pain, warm, and cold senses. The 2‐point discriminations were also recorded. For morphologic evaluation, the shapes of nerve fibers and nerve fiber bundles were observed and counted after immunohistochemical stains with S‐100 protein and neuron‐specific enolase and observed with transmission electron microscope.ResultsThe scores of the 5 subjective senses in the sensate flaps and 2‐point discrimination capabilities were significantly higher than those in the nonsensate flaps (p <.05). The number and the shape of the nerve fibers in the sensate flaps were more prominent (p <.05).ConclusionThere were significant differences in sensory recovery between sensate and nonsensate flaps in oral cavity and oropharyngeal reconstruction, and the nerve fibers were larger, better arranged, and more numerous in sensate than nonsensate flaps. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
A review of the micronutrient intervention cost literature: program design and policy lessons
Authors: Fiedler John L. , Sanghvi Tina G. , Saunders Margaret K. 
Published: April 2008

AbstractSince the 1993 publication of Disease Control Priorities in Developing Countries and World Development Report: Investing in Health, micronutrient fortification and supplementation interventions have been recognized as being among the most cost‐effective public health interventions. This paper reviews nearly 100 studies of the cost of micronutrient interventions. The literature contains enormous variation in the estimated costs of these programs due to differences in program structure, delivery systems and a host of country‐specific factors, differences in the studies' objectives, designs and costing methodologies. The most diverse estimates reported are those of vitamin A supplementation programs, where estimates vary by a factor of more than 1000. The costs of fortification programs, too, vary substantially from a factor of two for iodine, six for iron, and 15 for vitamin A fortification. As the magnitude of these variations suggests, the bulk of these studies are idiosyncratic, and their results are not directly comparable. The review highlights the need for greater specificity in discourse about these programs, and for greater transparency about cost estimation methods. The review provides several insights: (1) average costs are several‐fold higher than has traditionally been maintained; (2) fortificants account for 80% of annual, incremental costs of vitamin A fortification; (3) whereas 70% of those of vitamin A supplementation programs are personnel; (4) the imprecision of food fortification coverage and impact estimates owes primarily to the paucity of food consumption data. Addressing the food consumption information gap is an essential next step to improving micronutrient program policies: to better targeting programs and to devising more cost‐effective program portfolio mixes. Cost studies have a largely unrealized potential role to play in increasing program efficiency, coverage, and effectiveness. Copyright © 2008 John Wiley & Sons, Ltd.
Comparison of craving and withdrawal among four combination nicotine treatments
Authors: Schneider Nina G. , Cortner Chris , Gould Jessica L. , Koury Margaret A. , Olmstead Richard E. 
Published: April 2008

AbstractObjectiveTo assess the appearance of craving and withdrawal among four combination nicotine replacement treatments (NRTs).MethodsIn a crossover trial of NRT preferences, 27 smokers tested 4 combinations of nicotine treatments: 2 mg/4 mg gums + 15 mg patch, 2 mg/4 mg lozenges + 15 mg patch, inhalers + 15 mg patch, and 10 + 15 mg double patch (∼25 mg). Overnight abstinence was required prior to ½ day testing of each combination. Combination NRTs were used for ∼6 h/day. Subjects resumed smoking each afternoon. For this report, we used the Smoker Anchored Withdrawal Grid to look at craving and withdrawal scores over 5 days of testing (smoking baseline + four treatment days).Results“Urge to smoke” and “total withdrawal” showed a rise from baseline to NRT use for the double patch but not for the three acute + patch conditions. Lozenge/patch scores did not rise from baseline for “craving” and “miss a cigarette” but did for gum/patch, inhaler/patch, and double patch. The best relief occurred for NRTs of choice.ConclusionThis was a small but suggestive finding regarding the potential of patch plus adjunct ad lib NRT. With little data on relief with NRT combinations, more systematic tests are needed. Published in 2008 by John Wiley & Sons, Ltd.
Ultrahigh molecular weight polyethylene wear debris inhibits osteoprogenitor proliferation and differentiation in vitro
Authors: Chiu Richard , Ma Ting , Smith R. Lane , Goodman Stuart B. 
Published: April 2008

AbstractPolyethylene wear debris induces progressive osteolysis by increasing bone degradation and suppressing bone formation. Polyethylene particles inhibit the function of mature osteoblasts, but whether polyethylene particles also interfere with the proliferation and differentiation of osteoprogenitor cells is unknown. In this study, we investigated the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on the osteogenic activity of primary murine bone marrow osteoprogenitors and MC3T3‐E1 preosteoblastic cells in vitro. Submicron‐sized UHMWPE particles generated from wear simulator tests were isolated from serum‐containing solution by density gradient centrifugation. The particles were coated onto the surface of culture wells at concentrations of 0.038, 0.075, 0.150, 0.300, and 0.600% v/v in a layer of type I collagen matrix. Primary murine bone marrow cells and MC3T3‐E1 preosteoblasts were seeded onto the particle‐collagen matrix and induced to differentiate in osteogenic medium for 20 days. Exposure of both cell populations to UHMWPE particles resulted in a dose‐dependent decrease in mineralization, proliferation, alkaline phosphatase activity, and osteocalcin production when compared with control cells cultured on collagen matrix without particles. Complete suppression of osteogenesis was observed at particle concentrations ≥0.150% v/v. This study demonstrated that UHMWPE particles inhibit the osteogenic activity of osteoprogenitor cells, which may result in reduced periprosthetic bone regeneration and repair. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue‐to‐bone integration
Authors: Spalazzi Jeffrey P. , Dagher Elias , Doty Stephen B. , Guo X. Edward , Rodeo Scott A. , Lu Helen H. 
Published: April 2008

AbstractAchieving functional graft integration with subchondral bone poses a significant challenge for orthopaedic soft tissue repair and reconstruction. Soft tissues such as the anterior cruciate ligament (ACL) integrate with bone through a fibrocartilage interface, which minimizes stress concentrations and mediates load transfer between soft and hard tissues. We propose that biological fixation can be achieved by regenerating this fibrocartilage interface on biological or synthetic ACL grafts. This study focuses on the in vivo evaluation of a stratified scaffold predesigned to mimic the multitissue transition found at the ACL‐to‐bone interface. Specifically, the scaffold consists of three distinct yet continuous phases: Phase A for ligament formation, Phase B for the interface, and Phase C for the bone region. Interface‐relevant cell types, specifically fibroblasts, chondrocytes, and osteoblasts, will be tri‐cultured on this scaffold, and the formation of cell type‐ and phase‐specific matrix heterogeneity as well as fibrocartilage formation will be evaluated over 8 weeks in a subcutaneous athymic rat model. Acellular scaffolds as well as scaffolds co‐cultured with fibroblasts and osteoblasts will serve as controls. It was found that the triphasic scaffold supported multilineage cellular interactions as well as tissue infiltration and abundant matrix production in vivo. In addition, controlled phase‐specific matrix heterogeneity was induced on the scaffold, with distinct mineral and fibrocartilage‐like tissue regions formed in the tri‐cultured group. Cell seeding had a positive effect on both host infiltration and matrix elaboration, which also translated into increased mechanical properties in the seeded groups compared to the acellular controls. In summary, the biomimetic and multiphasic design coupled with spatial control of cell distribution enables multitissue regeneration on the stratified scaffold, and demonstrates the potential for regenerating the interface between soft tissue grafts and bone. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Inactivation of the p19ARF tumor suppressor affects intestinal epithelial cell proliferation and integrity
Authors: Farmer Tiffany E. , Williams Christopher S. , Washington M. Kay , Hiebert Scott W. 
Published: April 2008

Abstractp19ARF is a tumor suppressor that is frequently deleted in human cancer. It lies at chromosome 9p21 and shares exons 2 and 3 with p16ink4a, which is also inactivated by these cancer‐associated deletions. The “canonical pathway” by which p19ARF is thought to suppress tumorigenesis through activation of the p53 tumor suppressor. In response to hyperproliferative signals, such as expression of oncogenes, p19ARF is induced and binds to the MDM2 ubiquitin ligase, sequestering it in the nucleolus to allow the accumulation of p53. However, p19ARF also has MDM2 and p53 independent functions. In human colon cancer, p19ARF is only rarely deleted, but it is more frequently silenced by DNA promoter methylation. Here we show that inactivation of p19ARF in mice increases the number of cycling cells in the crypts of the colonic epithelium. Moreover, inactivation of p19ARF exacerbated the ulceration of the colonic epithelium caused by dextran sodium sulfate (DSS). These effects were similar to those observed in mice lacking myeloid translocation gene‐related‐1 (Mtgr1), and mice lacking both of these genes showed an even greater sensitivity to DSS. Surprisingly, inactivation of p19ARF restored the loss of the secretory lineage in mice deficient in Mtgr1, suggesting an additional role for p19ARF in the small intestinal epithelium. J. Cell. Biochem. 104: 2228–2240, 2008. © 2008 Wiley‐Liss, Inc.
Sparc localizes to the blebs of hobit cells and human primary osteoblasts
Authors: Baldini Giovanna , Ponti Cristina , Bortul Roberta , Narducci Paola , Grill Vittorio , Martelli Alberto M. 
Published: April 2008

AbstractSecreted protein acidic and rich in cystein (SPARC) is a secreted glycoprotein involved in several biological processes such as tissue remodeling, embryonic development, cell/extracellular matrix interactions, and cell migration. In particular, SPARC affects bone remodeling through the regulation of both differentiation/survival of osteoblasts and bone extracellular matrix synthesis/turnover. Here, we investigated SPARC subcellular localization in the human osteoblastic HOBIT cell line by immunocytochemistry and western blot analysis. We show that, under normal exponential cell growth conditions, SPARC localized both to cell nucleus and to cytoplasm, with no co‐localization on actin stress fibers. However, in colchicine‐treated HOBIT cells and human primary osteoblasts undergoing blebs formation, SPARC showed a different cellular distribution, with an additional marked compartmentalization inside the blebs, where it co‐localized with globular actin and actin‐binding proteins such as α‐actinin, cortactin, and vinculin. Moreover, we demonstrate by an in vitro assay that the addition of SPARC to actin and α‐actinin inhibited the formation of cross‐linked actin filaments and disrupted newly formed filaments, most likely due to a direct interaction between SPARC and α‐actinin, as indicated by immunoprecipitation assay. The specific silencing of SPARC RNA expression markedly decreased the ability of colchicine‐treated HOBIT cells to undergo blebbing, suggesting a direct role for SPARC in cell morphology dynamics during cytoskeletal reorganization. J. Cell. Biochem. 104: 2310–2323, 2008. © 2008 Wiley‐Liss, Inc.
UBE1DC1, an ubiquitin‐activating enzyme, activates two different ubiquitin‐like proteins
Authors: Zheng Mei , Gu Xing , Zheng Dan , Yang Zhenxing , Li Fan , Zhao Jun , Xie Yi , Ji Chaoneng , Mao Yumin 
Published: April 2008

AbstractUbiquitin and ubiquitin‐like proteins are known to be covalently conjugated to a variety of cellular substrates via a three‐step enzymatic pathway. These modifications lead to the degradation of substrates or change its functional status. The ubiquitin‐activating enzyme (E1) plays a key role in the first step of ubiquitination pathway to activate ubiquitin or ubiquitin‐like proteins. Ubiquitin‐activating enzyme E1‐domain containing 1 (UBE1DC1) had been proved to activate an ubiquitin‐like protein, ubiquitin‐fold modifier 1 (Ufm1), by forming a high‐energy thioester bond. In this report, UBE1DC1 is proved to activate another ubiquitin‐like protein, SUMO2, besides Ufm1, both in vitro and in vivo by immunological analysis. It indicated that UBE1DC1 could activate two different ubiquitin‐like proteins, SUMO2 and Ufm1, which have no significant similarity with each other. Subcellular localization in AD293 cells revealed that UBE1DC1 was especially distributed in the cytoplasm; whereas UBE1DC1 was mainly distributed in the nucleus when was cotransfected with SUMO2. It presumed that UBE1DC1 greatly activated SUMO2 in the nucleus or transferred activated‐SUMO2 to nucleus after it conjugated SUMO2 in the cytoplasm. J. Cell. Biochem. 104: 2324–2334, 2008. © 2008 Wiley‐Liss, Inc.
PRIMA‐1 synergizes with adriamycin to induce cell death in non‐small cell lung cancer cells
Authors: Magrini R. , Russo D. , Ottaggio L. , Fronza G. , Inga A. , Menichini P. 
Published: April 2008

Abstractp53‐dependent apoptosis is important for the efficacy of cancer treatment, and tumors carrying mutant p53 are often resistant to chemotherapy. Non‐small cell lung cancer (NSCLC) cells generally exhibit resistance to apoptosis following treatment with many cytotoxic drugs. The new molecule PRIMA‐1 appears to kill human tumor cells by restoring the transcriptional activity to mutated p53. We investigated the induction of apoptosis in response to this drug in three NSCLC cell lines carrying different p53 proteins: A549 (p53wt), LX1 (p53R273H), and SKMes1 (p53R280K). PRIMA‐1 alone did not trigger apoptosis but significantly reduced cell viability. However, in combination with adriamycin, PRIMA‐1 strengthen the adriamycin‐induced apoptosis in A549 and LX1. Interestingly, even in SKMes1 cells, the combined treatment triggered a strong PARP cleavage without DNA fragmentation. Our data suggest that in NSCLC cells, PRIMA‐1 may induce cell death through pathways other than apoptosis but may synergize with adriamycin to trigger an apoptotic response. J. Cell. Biochem. 104: 2363–2373, 2008. © 2008 Wiley‐Liss, Inc.
Ab initio computational study of positron emission tomography ligands interacting with lipid molecule for the prediction of nonspecific binding
Authors: Rosso Lula , Gee Antony D. , Gould Ian R. 
Published: April 2008

AbstractNonspecific binding is a poorly understood biological phenomenon of relevance in the study of small molecules interactions in vivo and in drug development. Nonspecific binding is thought to be correlated in part to a molecule's lipophilicity, typically estimated by measuring (or calculating) octanol–water partition coefficient. This is, however, a gross simplification of a complex phenomenon. In this article, we present a computational method whose aim is to help identify positron emission tomography (PET) ligands with low nonspecific binding characteristics by investigating the molecular basis of ligand–membrane interaction. We considered a set consisting of 10 well‐studied central nervous system PET radiotracers acting on a variety of molecular targets. Quantum mechanical calculations were used to estimate the strength of the interaction between each drug molecule and one phospholipid molecule commonly present in mammalian membranes. The results indicate a correlation between the computed drug–lipid interaction energy and the in vivo nonspecific distribution volume relative to the free tracer plasma concentration, calculated using standard compartmental modeling for the analysis of PET data. Significantly, the drugs whose interaction with the lipid molecule more favorably possessed, in general, a higher nonspecific binding value, whereas for the drugs taken in consideration in this study, the water‐octanol partition coefficient, log P, did not show good predictive power of the nonspecific binding. This study also illustrates how ab initio chemical methods may offer meaningful and unbiased insights for the understanding of the underlying chemical mechanisms in biological systems. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
The trans effect in square‐planar platinum(II) complexes—A density functional study
Authors: Chval Zdenek , Sip Miroslav , Burda Jaroslav V. 
Published: April 2008

AbstractThe mechanism of substitution water exchange reactions in square planar trans‐Pt[(NH3)2T(H2O)]n+ complexes is studied (TH2O, NH3, OH−, F−, Cl−, Br−, H2S, CH3S−, SCN−, CN−, PH3, CO, CH3−, H−, C2H4). The trans effect is explained in terms of σ‐donation and π‐back‐donation whose relative strengths are quantified by the changes of electron occupations of 5d platinum atomic orbitals. The σ‐donation strength is linearly correlated with the PtH2O (leaving ligand) bond length (trans influence). The kinetic trans effect strength correlates proportionally with the σ‐donation ability of the trans‐ligand except the ligands with strong π‐back‐donation ability that stabilizes transition state structure. The σ‐donation ability of the ligand is dependent on the σ‐donation strength of the ligand in the trans position. Therefore the trans effect caused by σ‐donation can be understood as a competition between the trans‐ligands for the opportunity to donate electron density to the central Pt(II) atom. The influence of the trans effect on the reaction mechanism is also shown. For ligands with a very strong σ‐donation (e.g. CH3− and H−), the substitution proceeds by a dissociative interchange (Id) mechanism. Ligands with strong π‐back donation ability (e.g. C2H4) stabilize the pentacoordinated intermediate and the substitution proceeds by a two step associative mechanism. For ligands with weak σ‐donation and π‐back‐donation abilities, the highest activation barriers have to be overcome and substitutions can be described by an associative interchange (Ia) mechanism. The results are supported by the energy decomposition and the natural orbital analysis. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008