bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin‐4: Analysis of the functional collagen promoter sequences
Authors: Büttner Cordula , Skupin Annett , Rieber Ernst Peter 
Published: November 2003

AbstractPneumonitis followed by lung fibrosis is a frequent complication of radiation therapy of chest tumors. A hallmark of these fibrotic lesions is the excessive production and accumulation of extracellular matrix proteins such as type I collagen. In addition to TGF‐β1, IL‐4 has been recognized as a potent inducer of collagen gene synthesis in fibroblasts. In this study, we analyzed the regulation of the α1(I) procollagen (COL1A1) promoter and the α2(I) procollagen (COL1A2) promoter by IL‐4 in normal human lung fibroblasts. We provide evidence that the IL‐4‐induced transcriptional activator STAT6 binds to various sequences within the COL1A1 and COL1A2 promoter. The regulatory function of these regions was tested by reporter gene analysis using 5′ deletions of the COL1A1 and COL1A2 promoter fused to the luciferase gene. Interleukin‐4 treatment of human fibroblasts transiently transfected with COL1A1 promoter deletion constructs resulted in luciferase activity exceeding that of untreated fibroblasts by 25%, while luciferase activity driven by the COL1A2 promoter was enhanced by about 70% upon IL‐4 treatment. A combined action of SP1, NFκB, and STAT6 essentially contributes to the IL‐4 mediated COL1A2 gene activation. An AP2 site adjacent to the reverse orientated STAT6 consensus motif TTC N3/4 GCT is located within 205 bases from the transcription start site and seems to support the moderate IL‐4‐induced COL1A1 gene activation. Interferon‐γ downregulation of transcription is mainly seen with the COL1A1 promoter. J. Cell. Physiol. 198: 248–258, 2004© 2003 Wiley‐Liss, Inc.
Inhibition of estrogen receptor alpha expression and function in MCF‐7 cells by kaempferol
Authors: Hung Huynh 
Published: November 2003

AbstractEstrogens are mitogenic for estrogen receptor (ER)‐positive breast cancer cells. Current treatment of ER‐positive breast tumors is directed towards interruption of estrogen activity. We report that treatment of ER‐positive breast cancer cells with kaempferol resulted in a time‐ and dose‐dependent decrease in cell number. The concentration required to produce 50% growth inhibition at 48 h was approximately 35.0 and 70.0 μM for ER‐positive and ER‐negative breast cancer cells, respectively. For MCF‐7 cells, a reduction in the ER‐α mRNA equivalent to 50, 12, 10% of controls was observed 24 h after treatment with 17.5, 35.0, and 70.0 μM of kaempferol, respectively. Concomitantly, these treatments led to a 58, 80, and 85% decrease in ER‐α protein. The inhibitory effect of kaempferol on ER‐α levels was seen as early as 6 h post‐treatment. Kaempferol treatment also led in a dose‐dependent decrease in the expression of progesterone receptor (PgR), cyclin D1, and insulin receptor substrate 1 (IRS‐1). Immunocytochemical study revealed that ER‐α protein in kaempferol‐treated MCF‐7 cells formed an aggregation in the nuclei. Kaempferol also induced degradation of ER‐α by a different pathway than that were observed for the antiestrogen ICI 182,780 and estradiol. Estradiol‐induced MCF‐7 cell proliferation and expression of the estrogen‐responsive‐element‐reporter gene activity were abolished in cells co‐treated with kaempferol. These findings suggest that modulation of ER‐α expression and function by kaempferol may be, in part, responsible for its anti‐proliferative effects seen in in vitro. J. Cell. Physiol. 198: 197–208, 2004© 2003 Wiley‐Liss, Inc.
Geldanamycin, a heat shock protein 90‐binding agent, disrupts Stat5 activation in IL‐2‐stimulated cells
Authors: Xu Weijing , Yu Furong , Yan Mingda , Lu Linrong , Zou Weiguo , Sun Lanying , Zheng Zhongcheng , Liu Xinyuan 
Published: November 2003

AbstractThe 90‐kDa heat shock protein (Hsp90) is the most abundant molecular chaperone in eukaryotic cells. Hsp90 plays a critical role in regulating signal transduction pathways that control cell proliferation since its chaperone function is restricted to a subset of proteins including some signal molecules. Improper function of these proteins can be induced by an anti‐tumor agent geldanamycin (GA) which is the specific inhibitor of Hsp90. In this study, it was demonstrated that GA interferes with IL‐2‐stimulated proliferation of murine CTLL‐2 cells. As to the signaling mechanisms underlying this inhibitory effect, we discovered GA disrupts the IL‐2‐stimulated activation and phosphorylation of the transcription factor Stat5, indicating the proper function of Hsp90 is indispensable for Stat5 activation. This conclusion is validated by the observation that Hsp90 interacts with Stat5 in the immunoprecipitation assay and GA interrupts their interaction. Furthermore, by constructing deletion mutants, we identified the c‐terminal half of Stat5 coiled‐coil region is responsible for binding with Hsp90. J. Cell. Physiol. 198: 188–196, 2004© 2003 Wiley‐Liss, Inc.
Characterization of p21Ras‐mediated apoptosis induced by protein kinase C inhibition and application to human tumor cell lines
Authors: Liou James S. , Chen James S. , Faller Douglas V. 
Published: November 2003

AbstractSuppression of PKC activity can selectively induce apoptosis in cells expressing a constitutively activated p21Ras protein. We demonstrate that continued expression of p21Ras activity is required in PKC‐mediated apoptosis because farnesyltransferase inhibitors abrogated the loss of viability in p21Ras‐transformed cells occurring following PKC inhibition. Studies utilizing gene transfer or viral vectors demonstrate that transient expression of oncogenic p21Ras activity is sufficient for induction of apoptosis by PKC inhibition, whereas physiologic activation of p21Ras by growth factor is not sufficient to induce apoptosis. Mechanistically, the p21Ras‐mediated apoptosis induced by PKC inhibition is dependent upon mitochondrial dysregulation, with a concurrent loss of mitochondrial membrane potential (ψm). Cyclosporine A, which prevented the loss of ψm, also inhibited HMG‐induced DNA fragmentation in cells expressing an activated p21Ras. Induction of apoptosis by PKC inhibition in human tumors with oncogenic p21Ras mutations was demonstrated. Inhibition of PKC caused increased apoptosis in MIA‐PaCa‐2, a human pancreatic tumor line containing a mutated Ki–ras allele, when compared to HS766T, a human pancreatic tumor line with normal Ki–ras alleles. Furthermore, PKC inhibition induced apoptosis in HCT116, a human colorectal tumor line containing an oncogenic Ki–ras allele but not in a subline (Hke3) in which the mutated Ki–ras allele had been disrupted. The PKC inhibitor 1‐O‐hexadecyl‐2‐O‐methyl‐rac‐glycerol (HMG), significantly reduced p21Ras‐mediated tumor growth in vivo in a nude mouse MIA‐PaCa‐2 xenograft model. Collectively these studies suggest the therapeutic feasibility of targeting PKC activity in tumors expressing an activated p21Ras oncoprotein. J. Cell. Physiol. 198: 277–294, 2004. © 2003 Wiley‐Liss, Inc.
Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (‘Iressa’) is independent of EGFR expression level
Authors: Campiglio Manuela , Locatelli Alberta , Olgiati Clelia , Normanno Nicola , Somenzi Giulia , Viganò Lucia , Fumagalli Marzia , Ménard Sylvie , Gianni Luca 
Published: November 2003

AbstractHigh expression of the epidermal growth factor receptor (EGFR) in breast carcinoma confers a growth advantage to the tumor cells. The EGFR tyrosine kinase inhibitor (EGFR‐TKI) ZD1839 (‘Iressa’) has clinical activity in a wide range of tumor types, although the mechanism(s) by which it exerts its antitumor activity effects remain unclear. We analyzed the ability of ZD1839 to induce apoptosis and/or inhibition of proliferation in breast carcinoma cell lines, as well any association between this ability and the downregulation activity of MAPK and Akt, two recently proposed markers of ZD1839 activity. Proliferation, survival, and activation of Akt and MAPK were evaluated in six human breast cancer cell lines expressing various levels of EGFR and HER2 and exposed to ZD1839. EGFR and HER2 expression levels were determined using specific monoclonal antibodies and FACS analysis. The effects of ZD1839 were independent of EGFR expression levels, but were influenced by high HER2 expression. ZD1839 significantly reduced the rate of [3H]‐thymidine incorporation in the four sensitive cell lines, while apoptosis was also induced in two of these cell lines. No correlation was found between the cytostatic or cytotoxic effects of ZD1839 and its ability to downregulate MAPK and Akt activity in the tumor cell lines. Our data suggest that the antitumor activity of ZD1839 is due to a cytostatic effect, and involves apoptosis induction in a subset of sensitive cells only, and that neither MAPK nor Akt is a reliable marker of ZD1839 activity. J. Cell. Physiol. 198: 259–268, 2004© 2003 Wiley‐Liss, Inc.
Retinoic acid inhibits leukemia inhibitory factor signaling pathways in mouse embryonic stem cells
Authors: Tighe Ann P. , Gudas Lorraine J. 
Published: November 2003

AbstractRetinoic acid (RA) induces the differentiation of murine embryonic stem (ES) cells to cell types resembling those found in the early embryo. When cultured in the presence of leukemia inhibitory factor (LIF), ES cells are maintained in an undifferentiated (self‐renewing) state. Addition of RA to the culture media overrides the self‐renewing effects of LIF to induce ES cell differentiation. Therefore, we hypothesized that RA‐induced differentiation of ES cells may be accomplished by antagonism of LIF‐induced signaling pathways. We demonstrate that RA‐induced differentiation of CCE ES cells is associated with (1) downregulation of the LIF receptor (LIFR); (2) decreased tyrosine phosphorylation of signal transducer and activator of transcription 3 protein (Stat3); and (3) increased activation of extracellular regulated kinase (Erk1/2). We conclude that RA induces CCE ES cell differentiation in the presence of LIF, in part, by disrupting signaling between the LIFR/gp130 receptor and nuclear targets that are required to prevent ES cell differentiation. Our data indicate that RA‐induced inhibition of LIF signaling does not involve Erk1/2‐dependent actions. J. Cell. Physiol. 198: 223–229, 2004© 2003 Wiley‐Liss, Inc.
Exposure to 900 MHz electromagnetic field induces an unbalance between pro‐apoptotic and pro‐survival signals in T‐lymphoblastoid leukemia CCRF‐CEM cells
Authors: Marinelli F. , La Sala D. , Cicciotti G. , Cattini L. , Trimarchi C. , Putti S. , Zamparelli A. , Giuliani L. , Tomassetti G. , Cinti Caterina 
Published: November 2003

AbstractAn Erratum has been published for this article in Journal of Cellular Physiology 198: 479–480, 2004.It has been recently established that low‐frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high‐frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low‐ and high‐frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high‐frequency EMFs could affect in vitro cell survival, we cultured acute T‐lymphoblastoid leukemia cells (CCRF‐CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high‐frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro‐apoptotic and pro‐survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2–12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53‐dependent and ‐independent apoptotic pathways while longer continuous exposure (24–48 h) determined silencing of pro‐apoptotic signals and activation of genes involved in both intracellular (Bcl‐2) and extracellular (Ras and Akt1) pro‐survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self‐defense response triggered by DNA damage, could confer to the survivor CCRF‐CEM cells a further advantage to survive and proliferate. J. Cell. Physiol. 198: 324–332, 2004© 2003 Wiley‐Liss, Inc.
Radiosynthesis of a 2‐substituted 4,5‐dihydro‐1H‐[2‐11C] imidazole: the I2 imidazoline receptor ligand [11C] benazoline
Authors: Roeda D. , Hinnen F. , Dollé F. 
Published: November 2003

AbstractBenazoline (2‐naphthalen‐2‐yl‐4,5‐dihydro‐1H‐imidazole) is a selective high‐affinity ligand for the imidazoline I2 receptor. This compound was labelled with carbon‐11 (T1/2=20.4 min) at the number two carbon atom of its 2‐imidazoline ring. Cyclotron‐produced [11C]carbon dioxide reacted with 2‐naphthylmagnesium bromide to give 2‐[carboxyl‐11C]naphthoic acid in 60% radiochemical yield. The latter was heated with a mixture of ethylenediamine and its dihydrochloride at 300°C to give [11C]benazoline in 16% overall yield, relative to [11C]carbon dioxide and with a specific radioactivity of 54 GBq/μmol, decay corrected for end of irradiation. The procedure requires about 45 min from end of cyclotron irradiation. This method should be extendable to other imidazolines. Copyright © 2003 John Wiley & Sons, Ltd.
Structures of monolayers formed from different HS—(CH2)2—X thiols on gold, silver and copper: comparitive studies by surface‐enhanced Raman scattering
Authors: Kudelski Andrzej 
Published: November 2003

AbstractMolecules of 2‐aminoethanethiol (cysteamine, CYS), 2‐mercaptoethanol (MET), 3‐mercaptopropionic acid (MPA), sodium 2‐mercaptoethanesulphonate (MES) and 1‐propanethiol (PTH) were spontaneously chemisorbed on electrochemically activated silver, copper and gold surfaces. The structure of monolayers formed was studied with surface‐enhanced Raman scattering (SERS). In CYS and MPA monolayers the relative surface concentration of gauche conformers was higher than in MET, PTH and MES monolayers. This is probably due to double bonding to the metal surface by a fraction of adsorbed MPA and CYS molecules (via the sulphur moiety and the terminal carboxylic or amino group). In CYS, MET, MPA and PTH monolayers the surface concentration of trans conformers is significantly higher on Ag than on Au or Cu. The structures of MES monolayers on Ag, Au and Cu are similar, with very high surface concentrations of trans conformers. Statistically, the wavenumbers of ν(C–S) bands of both gauche and trans conformers are the highest on Au, slightly lower on Ag and the lowest for Cu. However the positions of ν(C–S) bands are also sensitive to the other parameters (e.g. C—C—S—metal torsion angle, the overall ordering of the monolayer). Therefore, the wavenumbers of ν(C–S) bands are not good indicators of differences in the interaction between chemisorbed thiols and the metal substrates. Desorption measurements suggest that part of the adsorbed molecules is bonded significantly weaker than the rest. Thiolate monolayers on Cu decomposed relatively easily, forming a layer of copper sulphide. The strength of adsorbed MPA acid is similar on all substrates. Copyright © 2003 John Wiley & Sons, Ltd.
C—H···O hydrogen bonds in liquid cyclohexanone revealed by the νCO splitting and the νC–H blue shift
Authors: Vaz Pedro D. , Ribeiro‐Claro Paulo J. A. 
Published: November 2003

AbstractThe presence of C—H···O hydrogen bonds in liquid cyclohexanone is concluded from a combined theoretical and vibrational spectroscopic study. The two bands present in the νCO region, clearly observed in the Raman spectrum, are assigned to ‘free’ and ‘bonded’ carbonyl groups from their temperature‐dependent and solvent‐dependent relative intensities. In addition, a band exhibiting the same intensity dependence in the νC–H region is tentatively assigned to the blue‐shifted νC–H···(O) mode. Copyright © 2003 John Wiley & Sons, Ltd.
Resonance Raman characterization of cationic Co(II) and Co(III) tetrakis(N‐methyl‐4‐pyridinyl)porphyrins in aqueous and non‐aqueous media
Authors: Terekhov Sergei N. , Kruglik Sergei G. , Malinovskii Vladimir L. , Galievsky Victor A. , Chirvony Vladimir S. , Turpin Pierre‐Yves 
Published: November 2003

AbstractResonance Raman (RR) spectra of Co(II) and Co(III) complexes of the water‐soluble cationic tetrakis(N‐methyl‐4‐pyridinyl)porphyrin [CoIITMpyP(4), CoIIITMpyP(4)] were obtained in aqueous and non‐aqueous media, using both B‐ and Q‐band excitation wavelengths. RR spectra of CoIITMpyP(4) are observed for the first time, and they are compared with those of CoIIITMpyP(4). Wavenumbers of the ν2, ν4, ν8 and ν6 oxidation state‐sensitive bands depend on pH in aqueous solution and on the nature of the solvent (methanol, ethanol, DMF, DMSO): they lie in distinct spectral ranges for Co(II) vs Co(III) porphyrins. In addition, wavenumber shifts induced by axial ligation cover regions twofold broader for CoIIITMpyP(4) than for CoIITMpyP(4). This shows that the electronic influence of axial ligands on the π‐system of the macrocycle is more effective when cobalt is in a higher oxidation state. This can be due to (i) smaller axial bond lengths of Co(III) porphyrin and, hence, more efficient cobalt–axial ligand interaction as compared with Co(II) complexes, and (ii) CoIIITMpyP(4) being involved in bis‐adducts whereas CoIITMpyP(4) is mainly bound with only one axial ligand. The response of the porphyrin ring to the binding of axial ligands having various electron‐donating–withdrawing properties was monitored by the behaviour of these oxidation‐state sensitive RR bands: their shifts observed in a series of solvents were compared with Gutmann donor and acceptor numbers (DN, AN) of the solvents. A linear positive correlation was observed between Gutmann AN and ν2, ν4, ν8 and ν6 band wavenumbers for CoIIITMpyP(4), whereas a linear negative correlation was observed for the same bands of CoIITMpyP(4) when DN increases. This means that enhanced electron‐accepting properties of axial ligand result in a scarcity of cobalt dπ‐orbitals, which in turn leads to a decrease in π back‐donation from cobalt to the porphyrin macrocycle. Copyright © 2003 John Wiley & Sons, Ltd.
Raman scattering investigation of Yb : YAG crystals grown by the Czochralski method
Authors: Chen Y. F. , Lim P. K. , Lim S. J. , Yang Y. J. , Hu L. J. , Chiang H. P. , Tse W. S. 
Published: November 2003

AbstractRaman spectra of a series of Yb3+‐doped YAG crystals were obtained with Yb3+ concentrations up to 100 at.%. Single crystals were successfully grown. No abrupt change of the spectral pattern of the Raman modes as a function of Yb3+ doping concentration was observed. From the spectral changes, it is noted that the Raman peaks shift towards lower wavenumbers in the range <450 cm−1 and towards higher wavenumbers in the range >450 cm−1 with increasing Yb3+ doping concentration. It is proposed that Raman modes with wavenumbers <450 cm−1 are the yttrium or ytterbium ions lattice vibrational modes and that the other phonon peaks can then be assigned to internal modes associated with the (AlO4) tetrahedra of S4 symmetry. The doping concentration of Yb3+ does not influence the spectral properties and lattice vibrations drastically, so that a stable and more efficient Yb : YAG laser may be obtained with highly doped Yb3+ contents. Copyright © 2003 John Wiley & Sons, Ltd.
Time‐resolved resonance Raman study of S1cis‐stilbene and its deuterated isotopomers
Authors: Kwok W. M. , Ma C. , Phillips D. , Beeby A. , Marder T. B. , Thomas R. Ll. , Tschuschke C. , Baranović G. , Matousek P. , Towrie M. , Parker A. W. 
Published: November 2003

AbstractWe present the picosecond time‐resolved resonance Raman (ps‐TR3) spectra of the first excited singlet state (S1) of cis‐stilbene (d0), fully deuterated cis‐stilbene (d12) and α,α′‐d2‐cis‐stilbene (d2) measured in hexane at pump and probe wavelengths 267 and 630 nm, respectively. The main observation is that in the lower wavenumber region the spectra are dominated by a second‐order overtone progression originating from a 229 cm−1 fundamental band for the S1d0 cis‐stilbene. The observed low‐wavenumber modes of the excited cis‐stilbene are substantially more resonantly enhanced than the modes around 1600 cm−1. Copyright © 2003 John Wiley & Sons, Ltd.
Resonance Raman and time‐resolved resonance Raman spectra of the monomeric and dimeric complexes of ruthenium(II) with 2,3‐bis(2‐pyridyl)pyrazine (dpp)
Authors: Su Haiquan , Kincaid James R. 
Published: November 2003

AbstractThe electronic absorption, resonance Raman (RR) and time‐resolved resonance Raman (TR3) spectra of the monomeric and dimeric complexes of ruthenium(II) with 2,3‐bis(2‐pyridyl)pyrazine (dpp) were measured, i.e. Ru(bpy)2dpp2+ and Ru(bpy)2dppRu(bpy)24+, where bpy is 2,2′‐bipyridine. In addition, in order to facilitate definitive assignments of the observed RR spectral parameters, the corresponding selectively labeled complexes employing perdeuterated bpy (d8bpy) were also prepared and studied. It is shown that using judiciously chosen excitation lines to acquire the RR spectra permits selective enhancement of vibrational features associated with specific molecular fragments of the complexes, facilitating structural characterization of ground states of each complex. In addition, the TR3 spectrum of the monomeric complex yields vibrational signatures of its 3MLCT state, which is consistent with polarization of electron density towards the pyrazyl fragment; corresponding studies of the dimeric complex failed to provide conclusive evidence for modes attributable to an anion radical fragment, presumably owing to lack of effective enhancement with the excitation lines available. Copyright © 2003 John Wiley & Sons, Ltd.
LIFETIME COSTS FOR MEDICAL SERVICES: A METHODOLOGICAL REVIEW
Authors: Jacobs Philip , Golmohammadi Kamran , Longobardi Teresa 
Published: November 2003

Objectives: Guidelines for economic evaluation studies recommend that modeling be undertaken to estimate long-term, downstream costs. In this study, we conduct a review of a sample of studies that estimated the lifetime medical care costs for a variety of conditions.Methods: We developed a categorization of the elements for a lifetime-costing study and based on these elements, we abstracted information from a sample of 33 papers in the following areas: study subject, purpose, scope, methods (including time profile, utilization, and cost), and results.Results: We analyzed papers that were observational, models or that combined the two approaches. The time profiles were estimated from registry and published data. Utilization data were obtained from administrative data, chart reviews, and professional opinion. Costs were obtained from administrative and financial records and were estimated using all charges, allocated costs, and provider payments. We noted wide variations in methods and reporting practices.Conclusions: Following current guidelines (CCOHTA), lifetime models can be more easily interpreted and applied if investigators are more clear in their study aims, if they incorporate assumptions that are based on current data, if they follow current methodological practices (such as deflation, discounting, and sensitivity analyses), and if reporting is more transparent.