bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester
Authors: Fasani Elisa , Mella Mariella , Albini Angelo 
Published: December 2004

AbstractThe photochemistry of the fluoroquinolone drug lomefloxacin has been examined in aqueous solution in the presence of aliphatic amines (0.01 and 0.2 M) as well as 0.01 M NaOH; a fairly efficient decomposition (Φ = 0.2 to 0.4) takes place. Under the above conditions the product distribution is the same and differs from that previously observed in neutral and acidic aqueous solution. Five products have been characterized, all of them resulting from reductive elimination of the fluorine in the 8‐position and some alteration of the piperazine side‐chain. All of the products are rationalized as resulting from the heterolytic cleavage of the C8−F bond in triplet lomefloxacin to give the corresponding triplet aryl cation. Due to the multiplicity, the C8 site has a carbene rather than a localized cation character. Under these conditions — the amino group in the 4′‐position is free — the main process is formal hydride transfer from the 3′‐position and the minor one attack of the 4′‐amino group at the C6−F bond. In accordance with this rationalization, the methyl ester of lomefloxacin exhibits a closely analogous photochemistry under neutral conditions. The cationic intermediate may be involved in the observed phototoxicity of the drug, via an oxygen‐independent path. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
An Expeditious Asymmetric Synthesis of Polyfunctional 1,7‐Dioxaspiro[5.5]undecanes
Authors: Gerber‐Lemaire Sandrine , Vogel Pierre 
Published: December 2004

AbstractQuick access to polyfunctional spiroketal (3R)‐4[(2S,6R,8R,10S)‐4,4‐bis(ethylthio)‐10‐hydroxy‐8‐(2‐hydroxyethyl)‐1,7‐dioxaspiro[5.5]undec‐2‐yl]butane‐1,3‐diol [(+)‐19] is now available through the stereoselective functionalization of enantiomerically pure protected tetrol (4R,4′R,6R,6′R)1,1′‐methylenebis[4‐[(benzyloxy)methoxy]‐6‐[(triethylsilyl)oxy]cyclohept‐1‐ene [(−)‐9], derived from 2,2′‐methylenedifuran. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Structural Analysis of a Novel Polysaccharide of the Lipopolysaccharide‐Deficient Extremophile Gram‐Negative Bacterium Thermus thermophilus HB8
Authors: Silipo Alba , Molinaro Antonio , De Castro Cristina , Ferrara Renata , Romano Ida , Nicolaus Barbara , Lanzetta Rosa , Parrilli Michelangelo 
Published: December 2004

AbstractA novel polysaccharide was isolated from the extremophile Gram‐negative bacterium Thermus thermophilus HB8. Its structural characterization employed compositional and methylation analyses, and 2D 1H and 13C NMR spectroscopy. Various chemical degradations (methanolysis and Smith degradation) were also carried out in order to depolymerise this complex macromolecule, and subsequent chemical and spectroscopic analyses were also carried out on the obtained fragments. All the data suggested a novel polymeric structure that consists of a disaccharide repeating unit to which a branching trisaccharide chain is linked, although not stoichiometrically. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Selective Potentiometric Measurement of Physiologically Significant Thiols
Authors: Gracheva Svetlana , Digga Alkmini , Livingstone Callum , Davis James 
Published: December 2004

AbstractThe reaction of benzoquinone with reduced thiol species has been investigated using potentiometric techniques. The specificity of this reaction for thiol functionality has been briefly assessed and the nature of the electrode response has been elucidated. The system has been characterized in terms of selectivity, sensitivity and the efficacy of using the system for the quantification of thiol containing pharmaceuticals has been demonstrated. The simplicity of the detection methodology is shown to markedly contrast alternative thiol detection strategies. The transfer of the technology to a mass production format through the adoption of screen print electrode formats has been achieved and the efficacy of the approach demonstrated. Recovery experiments using captopril and penicillamine in tissue culture as a model analyte system were performed.
Efficacy of a rapamycin analog (CCI‐779) and IFN‐γ in tuberous sclerosis mouse models
Authors: Lee Laifong , Sudentas Paul , Donohue Brian , Asrican Kirsten , Worku Aelaf , Walker Victoria , Sun Yanping , Schmidt Karl , Albert Mitchell S. , El‐Hashemite Nisreen , Lader Alan S. , Onda Hiroaki , Zhang Hongbing , Kwiatkowski David J. , Dabora Sandra L. 
Published: December 2004

AbstractTuberous sclerosis complex (TSC) is a familial tumor disorder for which there is no effective medical therapy. Disease‐causing mutations in the TSC1 or TSC2 gene lead to increased mammalian target of rapamycin (mTOR) kinase activity in the conserved mTOR signaling pathway, which regulates nutrient uptake, cell growth, and protein translation. The normal function of TSC1 and TSC2 gene products is to form a complex that reduces mTOR kinase activity. Thus, mTOR kinase inhibition may be a useful targeted therapeutic approach. Elevated interferon‐gamma (IFN‐γ) expression is associated with decreased severity of kidney tumors in TSC patients and mouse models; therefore, IFN‐γ also has therapeutic potential. We studied cohorts of Tsc2+/− mice and a novel mouse model of Tsc2‐null tumors in order to evaluate the efficacy of targeted therapy for TSC. We found that treatment with either an mTOR kinase inhibitor (CCI‐779, a rapamycin analog) or with IFN‐γ reduced the severity of TSC‐related disease without significant toxicity. These results constitute definitive preclinical data that justify proceeding with clinical trials using these agents in selected patients with TSC and related disorders. © 2004 Wiley‐Liss, Inc.
Sequence of oligodendrocyte development in the human fetal telencephalon
Authors: Jakovcevski Igor , Zecevic Nada 
Published: December 2004

AbstractOligodendrocytes (OL), cells that myelinate axons in the CNS, differentiate from early to late oligodendrocyte progenitor cells (OPC) to become mature OL. Unlike the case in the rodent brain, myelin formation starts prenatally in the human brain, but the sequence of OL development and the onset of myelination are not well understood. We studied the human fetal forebrain at midgestation (17–23 gestational weeks, g.w.) using OL lineage‐specific antibodies and mRNA probes. Early OPC were present in a gradient from the subventricular zone to the cortical plate. Their close apposition to radial glia fibers suggests a possible role of these fibers in OPC migration. Late OPC reached peak density in the subplate layer, whereas multipolar cells with the morphology of mature OL were restricted to the emerging white matter. At 20 g.w., myelinated axons were observed in the diencephalon, but not in the telencephalon, consistent with caudal‐to‐rostral progression of myelination. Interestingly, in organotypic slice cultures of the same gestational ages, the subventricular zone contained a considerably greater number of the mature OL cells, suggesting the presence of inhibitory signals in vivo. Overall, in addition to considerable similarities with rodents, important differences in temporal and spatial distribution and regulatory signals for OL differentiation exist in the human brain. © 2004 Wiley‐Liss, Inc.
ATP binding cassette transporter ABC1 is required for the release of interleukin‐1β by P2X7‐stimulated and lipopolysaccharide‐primed mouse Schwann cells
Authors: Marty Vincent , Médina Chantal , Combe Chantal , Parnet Patricia , Amédée Thierry 
Published: December 2004

AbstractSchwann cells are best known as myelinating glial cells of the peripheral nervous system, but they also participate actively in the sphere of immunity by producing pro‐inflammatory cytokines, such as interleukin‐1β (IL‐1β). In a previous study, we demonstrated that posttranslational processing of IL‐1β by immune‐challenged Schwann cells required the P2X7 receptor. Remarkably, the release of IL‐1β was not associated with cell death, indicating the involvement of an active mechanism. ATP binding cassette (ABC) transporters are known to transport leaderless secretory proteins, such as IL‐1β; therefore, we investigated whether such transporters were at work in Schwann cells. Mouse Schwann cells expressed ABC1 transporter mRNA and displayed the functional protein. Glybenclamide and diisothiocyanato‐stilbene‐disulfonic acid (DIDS), two blockers of chloride fluxes that drive the export activity of ABC1 transporters, inhibited IL‐1β release without altering its intracellular processing. Enhancing chloride efflux potentiated the release of IL‐1β, while decreasing it led to a strong reduction in its release. Because the stimulation of the P2X7 receptor also activates a chloride conductance, we investigated the possibility of a sole anionic pathway mobilized by the P2X7 receptor and ABC1. Glybenclamide and DIDS had no significant effects on the P2X7‐activated chloride current suggesting therefore the existence of two different pathways. In summary, ABC1 transporters are required for the release of IL‐1β by mouse Schwann cells. Being associated together with chloride conductance, P2X7 receptors and ABC1 transporters delineate a subtle and complex regulation of IL‐1β production in mammalian Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic interest for regulating IL‐1β activity in neuroinflammation disorders. GLIA, 2004. © 2004 Wiley‐Liss, Inc.
Constitutive nuclear localization of activated caspase 3 in subpopulations of the astroglial family of cells
Authors: Noyan‐Ashraf Mohammad Hossein , Brandizzi Federica , Juurlink Bernhard H.J. 
Published: December 2004

AbstractIn a study examining for apoptosis in spontaneously hypertensive rats (SHR), we observed the constitutive presence of activated caspase 3 in Bergmann glia. We then examined stroke‐prone SHR as well as the normotensive strains Wistar, Wistar Kyoto, and Sprague‐Dawley. In all these strains, we found that Bergmann glia expressed activated caspase 3 in nuclei. Furthermore, subpopulations of astrocytes in the granular layer of the cerebellar cortex, in the hippocampus, and spinal cord gray matter, particularly in the dorsal part of the dorsal horns, expressed nuclear activated caspase 3. This distribution corresponds to the distribution of astrocytes that express the glutamate transporter GLAST. We conclude that Bergmann glia and a subpopulation of astrocytes throughout the CNS express activated caspase 3 in nuclei to fulfill a yet‐to‐be defined non‐apoptotic function. GLIA. © 2004 Wiley‐Liss, Inc.
Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population
Authors: Papaconstantinou Ioannis , Theodoropoulos George , Gazouli Maria , Panoussopoulos Dimitris , Mantzaris Gerassimos J. , Felekouras Evangelos , Bramis John 
Published: December 2004

AbstractEpidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR=5.00, p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer. © 2005 Wiley‐Liss, Inc.
Nuclear or cytoplasmic expression of survivin: What is the significance?
Authors: Li Fengzhi , Yang Jie , Ramnath Nithya , Javle Milind M. , Tan Dongfeng 
Published: December 2004

AbstractGrowing evidence suggests that survivin expression in cancer cell nuclei may represent an important prognostic marker to predict disease outcome for cancer patients. Current reports in this research area, however, are inconsistent and propose opposing conclusions regarding the significance and prognostic value of survivin nuclear expression. The aim of our study is to review and discuss the data reported in the original publications. We have also provided new experimental data to support our view regarding the possible reasons for the observed inconsistencies in the literature. This would alert researchers to pay attention to potential pitfalls in the determination of nuclear or cytoplasmic expression of survivin for the future. © 2004 Wiley‐Liss, Inc.
p16INK4a promoter methylation and protein expression in breast fibroadenoma and carcinoma
Authors: Vinci Angela Di , Perdelli Luisa , Banelli Barbara , Salvi Sandra , Casciano Ida , Gelvi Ilaria , Allemanni Giorgio , Margallo Edoardo , Gatteschi Beatrice , Romani Massimo 
Published: December 2004

AbstractThe potential role of p16INK4a methylation in breast cancer is controversial whereas there are no data on fibroadenoma. To assess if inactivation of p16INK4a by promoter hypermethylation occurs in this hyperproliferative benign breast lesion or, on the contrary, it is strictly related to the carcinogenic process, we have tested the different histological components of 15 cases of fibroadenoma and the intraductal and infiltrating components of 15 cases of carcinoma and their adjacent non‐tumoral epithelium. All samples were obtained by laser‐assisted microdissection. The relationship between promoter methylation status, immunohistochemical protein expression and ki67 proliferative activity was evaluated for each lesion. Our data demonstrate that hypermethylation of p16INK4a promoter is a common event occurring at similar frequency in all the different histological areas of the benign and malignant breast lesions taken into exam. Conversely, protein p16 expression, although heterogeneously distributed within the section, is considerably higher in breast carcinoma as compared to fibroadenoma in both tumoral and non‐tumoral epithelia and stroma. The protein localization was almost exclusively nuclear in fibroadenoma and non‐tumoral epithelia whereas, in carcinoma, the staining was both nuclear and cytoplasmic or cytoplasmic alone. Furthermore, in a subset of fibroadenoma with higher proliferative activity, p16 protein expression was substantially decreased as compared to those showing lower proliferation. We did not observe this association in carcinomas. Our data demonstrate that the hypermethylation of the p16INK4a promoter is not specifically associated with malignancy and that, on the contrary, the overexpression of p16 and its cytoplasmic sequestration is a feature of breast carcinoma. © 2004 Wiley‐Liss, Inc.
Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid
Authors: Camphausen Kevin , Cerna David , Scott Tamalee , Sproull Mary , Burgan William E. , Cerra Michael A. , Fine Howard , Tofilon Philip J. 
Published: December 2004

AbstractValproic acid (VA) is a well‐tolerated drug used to treat seizure disorders and has recently been shown to inhibit histone deacetylase (HDAC). Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we investigated the effects of VA on the radiosensitivity of human brain tumor cells grown in vitro and in vivo. The human brain tumor cell lines SF539 and U251 were used in our study. Histone hyperacetylation served as an indicator of HDAC inhibition. The effects of VA on tumor cell radiosensitivity in vitro were assessed using a clonogenic survival assay and γH2AX expression was determined as a measure of radiation‐induced DNA double strand breaks. The effect of VA on the in vivo radioresponse of brain tumor cells was evaluated according to tumor growth delay analysis carried out on U251 xenografts. Irradiation at the time of maximum VA‐induced histone hyperacetylation resulted in significant increases in the radiosensitivity of both SF539 and U251 cells. The radiosensitization was accompanied by a prolonged expression of γH2AX. VA administration to mice resulted in a clearly detectable level of histone hyperacetylation in U251 xenografts. Irradiation of U251 tumors in mice treated with VA resulted in an increase in radiation‐induced tumor growth delay. Valproic acid enhanced the radiosensitivity of both SF539 and U251 cell lines in vitro and U251 xenografts in vivo, which correlated with the induction of histone hyperacetylation. Moreover, the VA‐mediated increase in radiation‐induced cell killing seemed to involve the inhibition of DNA DSB repair. © 2004 Wiley‐Liss, Inc.
Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy
Authors: Takei Yoshifumi , Kadomatsu Kenji , Yuasa Kanako , Sato Waichi , Muramatsu Takashi 
Published: December 2004

AbstractOverexpression of a heparin‐binding growth factor, midkine (MK), has been observed in many malignancies, making it an attractive therapeutic target. We used morpholino antisense oligomers to downregulate human MK expression in human prostate (PC‐3) and colon carcinoma (SW620) cells, and determined the practical advantages of this anticancer therapeutic. Morpholino antisense oligomers directed against MK caused a dramatic and sequence‐specific decrease of the target protein level, resulting in the inhibition of growth and anchorage‐independent growth of the transfected cells. Furthermore, MK morpholino antisense oligomers exhibited a significant anticancer effect in the PC‐3‐ and SW620‐xenograft models. In comparison with phosphorothioate‐modified oligodeoxynucleotide, morpholino oligomers showed 2 major advantages, stability and non‐toxicity. MALDI‐TOF mass spectrometric analysis showed that morpholino antisense oligomers were completely stable in the presence of serum nuclease(s). Serological examinations demonstrated no toxicity of MK morpholino antisense oligomers. Our study indicates that inhibition of MK expression by morpholino antisense oligomer is a promising novel and safe therapeutic strategy for cancers. © 2004 Wiley‐Liss, Inc.
Enhancing growth human endothelial cells on Arg‐Gly‐Asp (RGD) embedded poly (ε‐caprolactone) (PCL) surface with nanometer scale of surface disturbance
Authors: Chung Tze‐Wen , Yang Min‐Gia , Liu Der‐Zen , Chen Wen‐Pin , Pan Chin‐I , Wang Shoei‐Shen 
Published: December 2004

AbstractTo explore the application of PCL for the engineering of soft tissues, the PCL surface was first embedded in an amphiphilic moiety and then grafted with RGD peptide to enhance the growth rate of human endothelial cells (HUVEC) on the surface. To graft cell‐adhesive peptide RGD on the PCL surface, the PCL surface was first etched by the selected solvent with only nanometer‐scale of surface disturbance, and simultaneously embedded with DSPE‐PEG [di‐stearoyl‐phosphatidyl‐ethanolamine‐methoxy‐poly (ethylene glycol)] moiety. Then the PCL‐PEG surface was photochemically grafted by GRGD to form PCL‐PEG‐RGD surface. PCL and the modified surfaces were characterized by surface morphology, surface disturbance, contact angles, ATR‐FTIR functional group analysis, and the growth rate of HUVEC. The surface disturbances of PCL and the modified surfaces were examined by atomic force microscope (AFM) and presented by the topography and a roughness parameter, Ra. The Ra values were 16.4 ± 3.0, 34.8 ± 1.6, and 12.8 ± 0.3 nm (n = 3) for PCL, PCL‐PEG, and PCL‐PEG‐RGD surfaces, respectively. The topographies of the surfaces and Ra values indicated that the PCL modified technique developed by this study resulted in only nanometer scale of surface disturbance. In addition to reducing surface disturbances, reducing contact angle from 73.7° ± 0.4 (n = 3) for the PCL surface to 56.9° ± 4.0 (n = 3) for the PCL‐PEG surface, and the ATR‐FTIR transmission spectra at 1660 cm−1 for shoulder of amine I of PCL‐PEG‐RGD surface both confirmed the successful modification of PCL surfaces. HUVECs adhered well and grew on the PCL‐PEG‐RGD surface after 36 h incubation, whereas other surfaces did not support growth. Moreover, the viability for the relative growth rate of HUVECs on the PCL‐PEG‐RGD surface analyzed by MTT assay showed 8.5 times greater growth than that of the unmodified one. In conclusion, a PCL‐PEG‐RGD surface for enhancing the growth rate of HUVECs has been prepared by a new technique that caused only a nanometer‐scale of surface disturbance. This technique and the PCL‐PEG‐RGD surface could be further applied to engineer soft tissues. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 213–219, 2005
Simulation of a compositional model for multiphase flow in porous media
Authors: Chen Zhangxin , Huan Guanren , Wang Hemei 
Published: December 2004

AbstractIn this article, we consider the simulation of a compositional model for three‐dimensional, three‐phase, multicomponent flow in a porous medium. This model consists of Darcy's law for volumetric flow velocities, mass conservation for hydrocarbon components, thermodynamic equilibrium for mass interchange between phases, and an equation of state for saturations. A discretization scheme based on the block‐centered finite difference method for pressures and compositions is developed. Numerical results are reported for the benchmark problem of the third comparative solution project (CSP) organized by the society of petroleum engineers (SPE). © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005.
On a finite element method for a compressible viscous flow in a MOCVD reactor
Authors: Duque Jairo 
Published: December 2004

AbstractWe propose a stable finite element method for approximating the flow of a chemically reacting gas mixture in an MOCVD (metal‐organic chemical vapor deposition) reactor. The flow is governed by the full compressible Navier‐Stokes equations extended by transport equations for the chemical species, the energy equations and the equation of state, together with boundary conditions providing information on the reactor geometry and experimental conditions. The equations form a semilinear system with a constraint for which the corresponding pressure term is not the Lagrangian multiplier. An application of our method to a real world model of growth of GaAs shows the consistency with experimental data. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005