bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and Theoretical Study of the Photophysics and Structures of Europium Cryptates Incorporating 3,3′‐Bi‐isoquinoline‐2,2′‐dioxide
Authors: Gawryszewska Paula , Malta Oscar L. , Longo Ricardo L. , Goncalves e Silva Fabiana R. , Alves Severino , Mierzwicki Krzysztof , Latajka Zbigniew , Pietraszkiewicz Marek , Legendziewicz Janina
Published: October 2004

A detailed photophysical study of [Eu⊂(biqO2.2.2)(CF3SO3)](CF3SO3)2⋅CH3CN⋅H2O (Eu⊂1) and two other types of cryptates incorporating three 3,3′‐biisoquinoline‐2,2′‐dioxide units has been performed. Structural crystallographic data of Eu⊂1, electronic structure calculations and theoretical models were used to obtain the intramolecular energy transfer rates and the appropriate set of rate equations, which was solved numerically. Quantum yields and decay lifetimes were obtained from these results and compared to the experimental data. The role of the ligand‐to‐metal charge transfer (LMCT) states was ascertained. A theoretical ligand field and intensity analysis was carried out and the results agree very well with the emission spectra. The molecular structures of the lanthanide cryptates were successfully modelled by the YIII ion using the restricted Hartree–Fock (RHF) method, with the advantage of dealing with closed‐shell systems. These molecular structures were used to explain the drastic differences in the photophysics of the three EuIII cryptates.
Azulene‐to‐Naphthalene Rearrangement: The Car–Parrinello Metadynamics Method Explores Various Reaction Mechanisms
Authors: Stirling András , Iannuzzi Marcella , Laio Alessandro , Parrinello Michele
Published: October 2004

We studied the thermal intramolecular and radical rearrangement of azulene to naphthalene by employing a novel metadynamics method based on Car–Parrinello molecular dynamics. We demonstrate that relatively short simulations can provide us with several possible reaction mechanisms for the rearrangement. We show that different choices of the collective coordinates can steer the reaction along different pathways, thus offering the possibility of choosing the most probable mechanism. We consider herein three intramolecular mechanisms and two radical pathways. We found the norcaradiene pathway to be the preferable intramolecular mechanism, whereas the spiran mechanism is the favored radical route. We obtained high activation energies for all the intramolecular pathways (81.5–98.6 kcal mol−1), whereas the radical routes have activation energies of 24–39 kcal mol−1. The calculations have also resulted in elementary steps and intermediates not yet considered. A few attractive features of the metadynamics method in studying chemical reactions are pointed out.
Pulsed‐Laser Production and Detection of Spin‐Polarized Hydrogen Atoms
Authors: Rakitzis* T. Peter
Published: October 2004

Spin‐polarized hydrogen (SPH) atoms have traditionally been produced and detected using complex experimental methods with poor time resolution. Recently, SPH has been produced by pulsed‐laser photodissociation of HCl using circularly polarized light. In combination with the proposed detection of SPH via polarized fluorescence, this approach should allow the production and spatially resolved detection of SPH with a higher sensitivity than that currently available, and with a time resolution in the nanosecond regime. This represents an improvement of several orders of magnitude over the existing methods.
Visual Observation of Contact‐Induced Intercrystalline Migration of Aromatic Species Adsorbed in Zeolites by Fluorescence Microscopy
Authors: Hashimoto Shuichi , Yamashita Shinji
Published: October 2004

Intercrystalline migration and a migration‐assisted chemical reaction of adsorbed aromatic species between zeolite particles in physical contact were visualized by fluorescence microscopy coupled with a particle manipulation technique. The luminescence color characteristics of particular zeolite particles originating from the specific photochemistry of adsorbed species was exploited to follow the migration of the molecules. Two examples are shown that are relevant to the visualization of the time‐dependent migration process: A one guest–two sets of zeolite crystals system: chrysene (Chry)‐loaded zeolite Na+‐X (the sodium form of zeolite X) crystals were placed in contact with unloaded Tl+‐X (thallium‐exchanged X) crystals and allowed to stand at room temperature. Initially, the blue fluorescence of Chry was detected only from the Na+‐X particles, but later, the development of green phosphorescence emission was discernible from the Tl+‐X, which suggests that Chry migrated from the Na+‐X to the Tl+‐X crystals. A two guest‐species systems: Electron‐donating Chry‐loaded Na+‐X crystals were placed in contact with electron‐accepting 1,2,4,5‐tetracyanobenzene (TCNB)‐loaded Na+‐X or Na+‐Y crystals. With time, the former system (Chry/Na+‐X and TCNB/Na+‐X) gave rise to the emission of Chry‐TCNB charge‐transfer complexes resulting mainly from the migration of Chry while the latter system (Chry/Na+‐X and TCNB/Na+‐Y) afforded the same emission resulting largely from the migration of TCNB. The present investigation reveals that there is a certain direction for guest migration depending on the zeolite host and the nature of host–guest or guest–guest interaction.
Accurate pKa Determination for a Heterogeneous Group of Organic Molecules
Authors: Schmidt am Busch Marcel , Knapp Ernst‐Walter
Published: October 2004

Single‐molecule studies that allow to compute pKa values, proton affinities (gas‐phase acidity/basicity) and the electrostatic energy of solvation have been performed for a heterogeneous set of 26 organic compounds. Quantum mechanical density functional theory (DFT) using the Becke‐half&half and B3 LYP functionals on optimized molecular geometries have been carried out to investigate the energetics of gas‐phase protonation. The electrostatic contribution to the solvation energies of protonated and deprotonated compounds were calculated by solving the Poisson equation using atomic charges generated by fitting the electrostatic potential derived from the molecular wave functions in vacuum. The combination of gas‐phase and electrostatic solvation energies by means of the thermodynamic cycle enabled us to compute pKa values for the 26 compounds, which cover six distinct chemical groups (carboxylic acids, benzoic acids, phenols, imides, pyridines and imidazoles). The computational procedure for determining pKa values is accurate and transferable with a root‐mean‐square deviation of 0.53 and 0.57 pKa units and a maximum error of 1.0 pKa and 1.3 pKa units for Becke‐half&half and B3 LYP DFT functionals, respectively.
Photon Counting Histogram: One‐Photon Excitation
Authors: Huang Bo , Perroud Thomas D. , Zare Richard N.
Published: October 2004

The photon counting histogram (PCH) analysis is a fluorescence fluctuation method that is able to characterize the brightness and concentration of different fluorescent species present in a liquid sample. We find that the PCH model using a three‐dimensional Gaussian observation volume profile is inadequate for fitting experimental data obtained from a confocal setup with one‐photon excitation. We propose an improved model, which is based on the correction to the observation volume profile for the out‐of‐focus emission. We demonstrate that this model is able to resolve different species present under a wide range of conditions. Attention is given to how this model allows the examination of the effects of different instrumental setups on the resolvability.
On the Quantum Nature of an Excess Proton in Liquid Hydrogen Fluoride
Authors: Raugei Simone , Klein Michael L.
Published: October 2004

Liquid hydrogen fluoride consists of chains of hydrogen‐bonded molecules. The nature of an excess proton in liquid HF, which is of interest not only for its own sake, but also in relation to superacid chemistry and to its behavior in water, has been studied using computer simulations. The methodology employed is the density‐functional‐theory‐based path‐integral Car–Parrinello ab initio molecular dynamics. The excess proton, which formally exists as a H2F+ or a H2F2+ defect in an HF chain, is found to strongly perturb the chain to which it is attached. Moreover, due to large zero‐point energy, the charge defect is largely delocalized over several HF molecules.
Cover Picture: In‐Situ Observation of Nanowire Growth from Luminescent CdTe Nanocrystals in a Phosphate Buffer Solution (ChemPhysChem 10/2004)
Authors: Volkov Yuri , Mitchell Siobhan , Gaponik Nikolai , Rakovich Yurii P. , Donegan John F. , Kelleher Dermot , Rogach Andrey L.
Published: October 2004

The cover picture shows a three‐dimensional confocal image of luminescent nanowires self‐assembled from CdTe nanocrystals of different sizes and, thus, different emission colors in a standard physiological phosphate‐buffered solution. The formation of nanowires was followed in situ, as described in the Communication by Rogach et al. on page 1600.
Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA‐4 expression
Authors: Birebent Brigitte , Lorho Richard , Lechartier Hélène , de Guibert Sophie , Alizadeh Mehdi , Vu Nicolas , Beauplet Alain , Robillard Nelly , Semana Gilbert
Published: October 2004

It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4+CD25+ T cell compartment. Here, we describe an original method to purify human CD4+CD25+CD152+ T lymphocytes as living cells by forcing the exportation of CTLA‐4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4+CD25+ T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4+CD25+CD152+ T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen‐specific T cells than CD4+CD25+CD152– T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA‐4, we demonstrate that indeed CTLA‐4 is involved in CD4+CD25+CD152+ T cell regulatory activity, while suppressive cytokines are not.
Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo
Authors: Oflazoglu Ezogelin , Swart David A. , Anders‐Bartholo Penny , Jessup Heidi K. , Norment Anne M. , Lawrence William A. , Brasel Kenneth , Tocker Joel E. , Horan Tom , Welcher Andrew A. , Fitzpatrick David R.
Published: October 2004

Programmed death‐1 ligand 2 (PD‐L2) is a ligand for programmed death‐1 (PD‐1), a receptor that plays an inhibitory role in T cell activation. Since previous studies have shown up‐regulation of PD‐L2 expression by Th2 cytokines, and asthma is driven by a Th2 response, we hypothesized that PD‐L2 might be involved in regulation of the immune response in this disease. We have found that lungs from asthmatic mice had sustained up‐regulation of PD‐1 and PD‐L2, with PD‐L2 primarily on dendritic cells. Although addition of PD‐L2‐Fc in vitro led to decreased T cell proliferation and cytokine production, administration of PD‐L2‐Fc in vivo in a mouse asthma model resulted in elevated serum IgE levels, increased eosinophilic and lymphocytic infiltration into bronchoalveolar lavage fluid, higher number of cells in the draining lymph nodes, and production of IL‐5 and IL‐13 from these cells. Although PD‐1 was expressed on regulatory T cells, PD‐L2‐Fc did not affect regulatory T cell activity in vitro. This study provides in vivo evidence of an exacerbated inflammatory response following PD‐L2‐Fc administration and indicates a potential role for this molecule in Th2‐mediated diseases such as asthma.
Prostaglandin E2 modulates the functional responsiveness of human monocytes to chemokines
Authors: Panzer Ulf , Uguccioni Mariagrazia
Published: October 2004

Prostaglandin E2 (PGE2) plays an important role in the immune response by modulating the complex interactions between leukocytes and tissue cells under inflammatory conditions. PGE2 may possibly influence pro‐inflammatory effects of chemokines and chemokine receptors that are among the main regulators of directional leukocyte migration. We analyzed whether PGE2 affects chemokine receptor expression on human monocytes and their functional responsiveness to inflammatory chemokines. Expression of CCR5 on monocytes was significantly reduced, whereas CCR2 and CXCR4 expression were not affected by PGE2. However, PGE2 treatment significantly increased the chemotactic response of monocytes to monocyte‐chemoattractant protein‐1 (MCP‐1), RANTES and stromal cell‐derived factor‐1 (SDF‐1). In addition, PGE2 induced a higher calcium mobilization and actin polymerization upon chemokine stimulation. To better characterize PGE2 effects, we used specific agonists for the PGE2 receptors (EP1 – EP4) characterized so far. The 11‐deoxy PGE1, an EP2 /EP4 ligand, could mimic the effects observed using PGE2. In contrast, the EP1 agonist, sulprostone, had not effects on monocytes, indicating that the effects of PGE2 are mediated by EP2/EP4 receptors. Monocytes acquire a higher functional responsiveness to MCP‐1, RANTES and SDF‐1 after exposure to PGE2, independently of the level of chemokine receptor expression. This mechanism might enhance the local monocyte recruitment under inflammatory conditions, and suggests specific PGE2 receptor EP2/EP4 antagonists as novel agents for the treatment of inflammatory diseases.
Frontline: Peripheral priming of alloreactive T cells by the direct pathway of allorecognition
Authors: Baratin Myriam , Bonin Karina , Daniel Claude
Published: October 2004

Recent studies, though controversial, have suggested that secondary lymphoid organs may not constitute an essential site for the initiation of immune responses to transplant antigens. However, this issue has never been examined in the context of direct and indirect allorecognition. Here, we characterized immune responses arising in draining lymph nodes and skin allografts, in a murine model based on a single T cell clonotype where these two pathways can be independently studied. In this model, graft rejection by the direct or the indirect pathway occurred with similar kinetics, although initiation of the alloreactive responses was clearly different. During indirect responses, expansion and activation of alloreactive T cells were first observed in draining lymph nodes, at day 7 post‐transplant, and graft‐infiltrating T cells were observed later, at day 11. In striking contrast, directly activated alloreactive T cells were detected at an early stage inside the graft, and only later in the draining lymph nodes, after skin allograft rejection was almost completed. These results suggest that sensitization of naive T cells through the direct pathway could take place outside secondary lymphoid organs.

See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425506
Phenotypic heterogeneity of antigen‐specific CD4 T cells under different conditions of antigen persistence and antigen load
Authors: Harari Alexandre , Vallelian Florence , Pantaleo Giuseppe
Published: October 2004

The factors responsible for the phenotypic heterogeneity of memory CD4 T cells are unclear. In the present study, we have identified a third population of memory CD4 T cells characterized as CD45RA+CCR7– that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono‐phenotypic CD45RA–CCR7+ or CD45RA–CCR7– CD4 T cell responses were associated with conditions of Ag clearance (tetanus toxoid‐specific CD4 T cell response) or Ag persistence and high load (chronic HIV‐1 and primary CMV infections), respectively. Multi‐phenotypic CD45RA–CCR7+, CD45RA–CCR7– and CD45RA+CCR7– CD4 T cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV‐1 infection in long‐term nonprogressors). The mono‐phenotypic CD45RA–CCR7+ response was typical of central memory (TCM) IL‐2‐secreting CD4 T cells, the mono‐phenotypic CD45RA–CCR7– response of effector memory (TEM) IFN‐γ‐secreting CD4 T cells and the multi‐phenotypic response of both IL‐2‐ and IFN‐γ‐secreting cells. The present results indicate that the heterogeneity of different Ag‐specific CD4 T cell responses is regulated by Ag exposure and Ag load.
Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation
Authors: Hewitt Susannah L. , High Frances A. , Reiner Steven L. , Fisher Amanda G. , Merkenschlager Matthias
Published: October 2004

To address how heritable patterns of gene expression are acquired during the differentiation of Th1 and Th2 cells, we analyzed the nuclear position of lineage‐restricted cytokine genes and their upstream regulators by 3‐dimensional fluorescence in situ hybridization. During Th1 differentiation, GATA‐3 and c‐maf loci, which encode upstream regulators of Th2 cytokines, were progressively repositioned to centromeric heterochromatin as defined by a γ‐satellite repeat probe and/or the nuclear periphery, compartments that have been associated with transcriptional repression. A third transcription factor locus, T‐bet, which controls Th1‐specific programs, was subject to de novo CpG methylation in a Th2 cell clone. In contrast, we did not find repositioning of the cytokine gene loci IL‐2, IL‐3, IL‐4 or IFN‐γ during T helper cell differentiation. Instead, IFN‐γ was constitutively associated with the nuclear periphery, even when primed for expression in Th1 cells. Our results suggest that Th1/Th2 lineage commitment and differentiation involve repositioning of the regulators of cytokine expression, rather than the cytokine genes themselves.
Commentary: Priming of alloreactive T cells – where does it happen?
Authors: Golshayan Dela , Lechler Robert
Published: October 2004

Host lymphocytes can recognize alloantigens directly on transplanted donor tissue or indirectly after these antigens are processed and presented on host APC. Here, we outline the features of alloresponses that distinguish them from responses to conventional antigens, then we discuss various study systems that have examined where the priming of alloreactive CD4+ and CD8+ T cells occurs. Finally, we discuss the implications of recent data which suggest that direct responses originate in the graft itself whereas indirect responses are initiated in the draining lymph nodes.

See accompanying article: http://dx.doi.org/10.1002/eji.200425309
Synthesis, Molecular Structure, and Olefin Polymerisation Activity of an Oxovanadium(V) Alkoxide with Unprecedented Chloride Bridging Ligands
Authors: Rosenthal Esther C. E. , Cui Huiling , Lange Katharina C. H. , Dechert Sebastian
Published: October 2004

The reaction of 2‐methoxyethanol or (2‐methoxyethanolato)lithium with VOCl3 yields the chloro‐bridged dinuclear complex [VOCl2(OCH2CH2OCH3)]2, which has been characterised spectroscopically and structurally by single‐crystal X‐ray diffraction analysis. This is the first reported structure of a neutral dinuclear oxovanadium complex connected by bridging chloro ligands. The orange complex is a precatalyst for the polymerisation of ethene and the oligomerisation of styrene. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Fluorescent Self‐Assembled Monolayers of Bis(salicylaldiminato)zinc(II) Schiff‐Base Complexes
Authors: Di Bella Santo , Leonardi Nicoletta , Consiglio Giuseppe , Sortino Salvatore , Fragalà Ignazio
Published: October 2004

The synthesis and fluorescence properties of novel bis(salicylaldiminato)zinc(II) Schiff‐base complexes is reported. Selfassembled monolayers (SAMs) of these complexes are obtained by reaction of coupling layers, functionalized quartz substrates and a derivatized precursor complex. A comparison between the integrated emission intensity of the SAM films and that of a suitable model compound in solution indicates molecular fluorescence retention of the ZnII Schiff bases on going from the solution phase to the monolayer. This is consistent with the absence of significant self‐quenching processes, as expected on the basis of the relatively high estimated surface coverage. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Acid‐Base Self‐Assembly Chemistry and Hydrogen Bonding Interactions Resulting in the Formation of a Tetranuclear Aggregate Containing Four Crystallographically Non‐Equivalent FeIII Centers
Authors: Tanase Stefania , Bouwman Elisabeth , Long Gary J. , Shahin Ahmed M. , Mills Allison M. , Spek Anthony L. , Reedijk Jan
Published: October 2004

The synthesis and characterization of a mononuclear iron(III) complex [Fe(Hphpz)Cl(CH3OH)] (1) and a tetranuclear assembly of a bis(μ‐hydroxo)‐bridged dinuclear iron(III) complex [{Fe(Hphpz)2(OH)}2][Fe(Hphpz)3]2 (2) with the ligand 3(5)‐methyl‐5(3)‐(2‐hydroxyphenyl)pyrazole (H2phpz) is reported. Compound 1 is converted into 2 in a methanol solution and in the presence of a base. The asymmetric unit of 2 consists of two independent [Fe(Hphpz)3] molecules and one dinuclear complex [Fe(Hphpz)2(OH)]2 containing two crystallographically non‐equivalent iron(III) ions; the three units are linked by N−H···O and O−H···O hydrogen bonding and stacking interactions to form a cluster with an approximate C2‐symmetry. The Mössbauer spectra of [{Fe(Hphpz)2(OH)}2][Fe(phpz)3]2 have been measured at 295 and 78 K and indicate the presence of four crystallographically distinct, but chemically similar iron(III) sites. The magnetic properties of this compound originate from the weak antiferromagnetic interaction between the FeIII ions of the [Fe(phpz)2(OH)]2 dimer (J = −2.8 cm−1). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The General Rule of Power Converted from Chemical Energy to Electrical Energy
Authors: Shen M. , Zhang J. , Scott K.
Published: October 2004

Electrochemical power sources are widely used to convert chemical energy to electrical energy. Here we report an equation to describe the electrical power characteristics i.e., potential vs. the current performance curves, namely polarization curves of electrochemical power sources. From this basic equation, we describe the performance curve of general electrochemical power sources with three power source parameters: E0: equilibrium potential; R: internal resistance; and K: power conversion coefficient. The calculated values from this equation agree with the performance curves of power sources such as different type of fuel cells and batteries. The concept of the power convert coefficient is a new criterion to evaluate and compare the characteristics and capacity of different electrochemical power sources.
Activation of Colloidal PtRu Fuel Cell Catalysts via a Thermal “Conditioning Process”
Authors: Bönnemann H. , Endruschat U. , Hormes J. , Köhl G. , Kruse S. , Modrow H. , Mörtel R. , Nagabhushana K. S.
Published: October 2004

The activation of platinum‐ruthenium (Pt‐Ru) fuel cell catalysts, which were made by supporting nanoscopic colloidal precursors on conductive carbon (Vulcan XC72) is brought about by reactive annealing (“conditioning process”) at 250–300 °C, in a particular set‐up. The tetraalkylammonium (A) or triorganoaluminium (B) protecting shell is cleaved from the Pt‐Ru metal surface in three mandatory steps under flowing argon, oxygen, and hydrogen (30 min each). Ex‐situ TEM micrographs were used to monitor changes in particle size during this conditioning process. Additionally, in‐situ X‐ray absorption spectroscopic measurements on the Pt LIII‐edge provided insight into the processes occurring in the metallic core of the particles. While a small increase in size is found with conditioning, the dominant structural change in both catalyst types (A and B) is a reduction in the disorder inside the metallic particles, particularly in those having organoaluminium‐protected nanoparticles (B). During oxidation under flowing oxygen, platinum atoms only undergo oxidation in the bimetallic Pt‐Ru catalyst type (B) while the platinum atoms in the bimetallic Pt‐Ru catalyst (A) remain strictly zerovalent. This difference may be attributed to differences in the internal structure of the as prepared colloidal particles (A and B) as evidenced from Pt LIII EXAFS‐data and XANES spectra.
Fuzzy Logic Applied to the Inverter of a SOFC Power Plant
Authors: Jurado F.
Published: October 2004

Solid‐oxide fuel cell (SOFC) units normally supply power to the local load centers but the excess power can also be exported to the regional power grid, adding to the capacity and stability of the overall grid system. A SOFC power plant is equipped with a pulse width modulation (PWM) inverter. This paper presents the design of a new fuzzy logic regulator for a three‐phase inverter, using the strategy of an inverter flux vector control method. Criteria for designing the fuzzy controller are given and a comparison with the hysteresis method is presented. The flux vector approach is to generate the command pulses for low ripple current and constant switching frequency.
Regional cerebral blood flow in children with attention deficit hyperactivity disorder: Comparison before and after methylphenidate treatment
Authors: Lee Jae Sung , Kim Boong Nyun , Kang Eunjoo , Lee Dong Soo , Kim Yu Kyeong , Chung June‐Key , Lee Myung Chul , Cho Soo Churl
Published: October 2004

Differences in brain activity of children with attention deficit hyperactivity disorder (ADHD) have been compared to normal healthy controls, suggesting neural correlates of cognitive/behavioral symptoms. Symptoms are improved with methylphenidate treatment but limited sources can be cited to show how brain activity in ADHD is altered after pharmacologic treatment. We investigated how long‐term oral medication of methylphenidate affects the resting regional cerebral blood flow (rCBF) in ADHD children, using single photon emission computerized tomography (SPECT). rCBF was decreased in the orbitofrontal cortex and middle temporal gyrus in the right hemisphere whereas it was increased in the dorsomedial prefrontal and somatosensory area bilaterally in drug‐naïve ADHD children compared to control child subjects. After treatment with methylphenidate, the extent of hyperperfusion in the somatosensory area was reduced and significant reduction of rCBF was found in the right striatum for the first time. Methylphenidate treatment also resulted in rCBF increase in superior prefrontal and reduction in ventral higher visual areas bilaterally. The results indicated that improving ADHD symptom after methylphenidate is associated with normalization of abnormally reduced orbitofrontal activity and abnormally increased somatosensory cortical activity. These changes were accompanied with reduced striatum activity lower than that of normal controls. These changes might be associated with improving ADHD to control attention and motor response to irrelevant environmental stimuli after methylphenidate treatment. Hum. Brain Mapp 24:157–164, 2005. © 2004 Wiley‐Liss, Inc.
To be or not to be NKT: Natural killer T cells in the liver
Authors: Exley Mark A. , Koziel Margaret James
Published: October 2004

Much of the hepatology literature to date has focused on the adaptive, antigen-specific response mediated by classical T-cell populations in both the protection and pathogenesis of liver disease. However, the liver is selectively enriched for cells representative of innate immunity, including natural killer T (NKT) cells. In particular, certain CD1d-reactive T cells are present at much higher frequencies in the liver than in the peripheral blood. Although these cells have previously been defined mostly on the basis of phenotypic markers, recent emerging literature regarding NKT cell populations has revealed considerable functional complexity. This review summarizes the recent literature regarding NKT cells, which may have important roles in a variety of liver diseases. Although there is an abundance of literature on the phenotype, distribution, and function of these cells in mice, much less is known about them in human health or liver diseases. (Hepatology 2004;40:1033-1040.)
PTFE-covered stents improve TIPS patency in Budd-Chiari syndrome
Authors: Hernández-Guerra Manuel , Turnes Juan , Rubinstein Pablo , Olliff Simon , Elias Elwyn , Bosch Jaime , García-Pagán Juan Carlos
Published: October 2004

Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an efficient portal-systemic derivative treatment for Budd-Chiari syndrome (BCS) patients uncontrolled by medical therapy. However, the main drawback of TIPS for this condition is a very high rate of shunt dysfunction. Recently, polytetrafluoroethylene (PTFE)-covered stents have been shown to reduce the incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients treated with bare or PTFE-covered stents. The study included 25 TIPS procedures (16 bare stents and 9 covered stents) with a median follow-up period of 20.4 months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE-covered stents (P = .005). The actuarial rates of primary patency in the bare-stent group were 19% at 1 year compared with 67% in the PTFE-covered stent group (P = .02; log-rank test). The number of additional interventional procedures to maintain TIPS patency was significantly greater in the bare-stent than in the PTFE-covered stent group (1.9 ± 1.2 vs. 0.6 ± 0.9; P = .007). The number of patients with clinical relapses was greater in the bare-stent group compared to the PTFE-covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In conclusion, PTFE-covered stents have a considerable advantage over bare stents for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower number of reinterventions, and fewer prosthesis requirements. PTFE-covered stents are preferable in patients with Budd-Chiari Syndrome. (Hepatology 2004;40:1197-1202.)
Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury
Authors: Sass Gabriele , Seyfried Stefan , Soares Miguel Parreira , Yamashita Kenichiro , Kaczmarek Elzbieta , Neuhuber Winfried L. , Tiegs Gisa
Published: October 2004

Induction of the heme-degrading enzyme heme oxygenase-1 (HO-1) has been shown to be beneficial in terms of improvement of liver allograft survival and prevention of CD95-mediated apoptosis in the liver. In the present study, we investigated the effects of HO-1, and its products carbon monoxide (CO), biliverdin (BV), and iron/ferritin, in a mouse model of inflammatory liver damage inducible by lipopolysaccharide (LPS) in mice sensitized with the hepatocyte-specific transcription inhibitor d-galactosamine (GalN). Our results show that HO-1 induction by cobalt-protoporphyrin-IX (CoPP) reduced cytokine expression, protected mice from liver injury, and prolonged survival. While in contrast to ferritin overexpression, single administration of the CO donor methylene chloride (MC) or of BV also protected mice from liver damage, only coadministration of both HO products prolonged survival and reduced the expression of cytokines, e.g., tumor necrosis factor (TNF) and interferon γ (IFN-γ). In conclusion, HO-1-induced prolongation of survival, but not the protection from liver damage, seems to be dependent on down-regulation of cytokine synthesis. (Hepatology 2004;40:1128-1135.)
Frequent inactivation of the tumor suppressor Kruppel-like factor 6 ( KLF6 ) in hepatocellular carcinoma
Authors: Kremer-Tal Sigal , Reeves Helen L. , Narla Goutham , Thung Swan N. , Schwartz Myron , Difeo Analisa , Katz Amanda , Bruix Jordi , Bioulac-Sage Paulette , Martignetti John A. , Friedman Scott L.
Published: October 2004

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, reflecting incomplete characterization of underlying mechanisms and lack of early detection. Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcription factor that is deregulated in multiple cancers through loss of heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients, one of whom was coinfected with hepatitis C virus), and other etiologies (14 patients) by determining the presence of LOH and mutations. Overall, LOH and/or mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was present in 39% of primary HCCs, and the mutational frequency was 15%. LOH and/or mutations were distributed across all etiologies of HCC evaluated, including patients who did not have cirrhosis. Functionally, wild-type KLF6 decreased cellular proliferation of HepG2 cells, while patient-derived mutants did not. In conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC, and its inactivation may contribute to pathogenesis in a significant number of these tumors. (Hepatology 2004;40:1047-1052.)
An efficient therapeutic approach to patients with acute promyelocytic leukemia using a combination of arsenic trioxide with low‐dose all‐trans retinoic acid
Authors: Wang Guanjun , Li Wei , Cui Jiuwei , Gao Sujun , Yao Cheng , Jiang Zhenyu , Song Yanqiu , Yuan Chang‐Ji , Yang Yan , Liu Ziling , Cai Lu
Published: October 2004

The use of arsenic trioxide (As2O3, ATO) combined with all‐trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low‐dose ATRA (LD‐ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD‐ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD‐ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side‐effects have been no worse with the combined ATO/LD‐ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD‐ATRA regimen is superior to either regimen given alone to patients with APL. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of chemisorbed hyaluronic acid directly immobilized on solid substrates
Authors: Suh Kahp Y. , Yang Jen Ming , Khademhosseini Ali , Berry David , Tran Thanh‐Nga T. , Park Hyongshin , Langer Robert
Published: October 2004

Hyaluronic acid (HA) has a number of potential biomedical applications in drug delivery and tissue engineering. For these applications, a prerequisite is to understand the characteristic of HA films directly immobilized to solid substrates. Here, we demonstrate that high molecular weight HA can be directly immobilized onto hydrophilic substrates without any chemical manipulation, allowing for the formation of an ultrathin chemisorbed layer. Hyaluronic acid is stabilized on these surfaces through hydrogen bonding between the hydrophilic moieties in HA [such as carboxylic acid (COOH) or hydroxyl (OH) groups] with silanol (SiOH), carboxylic acid or hydroxyl groups on the hydrophilic substrates. Despite the water solubility, the chemisorbed HA layer remained stable on glass or silicon oxide substrates for at least 7 days in phosphate‐buffered saline. Furthermore, HA immobilized on silicon and other dioxide surfaces in much higher quantities than other polysaccharides including dextran sulfate, heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, and alginic acid. This behavior is related to the molecular entanglement and intrinsic stiffness of HA as a result of strong internal and external hydrogen bonding as well as high molecular weight. These results demonstrate that HA can be used to coat surfaces through direct immobilization. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 292–298, 2005
Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C
Authors: Zang Ming‐Xi , Li Yong , Xue Li‐Xiang , Jia Hong‐Ti , Jing Hua
Published: October 2004

An intricate array of cell‐specific multiprotein complexes participate in programs of cell‐specific gene expression through combinatorial interaction with different transcription factors and cofactors. The dHAND basic helix‐loop‐helix (bHLH) transcription factor, which is essential for heart development and extra embryonic structures, is thought to regulate cardiomyocyte‐specific gene expression through combinatorial interactions with other cardiac‐restricted transcription factors such as GATA4 and NKX2.5. Here, we determine that dHAND also interacts with the myocyte enhancer binding factor‐2c (MEF2C) protein, which belongs to MADS‐box transcription factors and is essential for heart development. dHAND and MEF2C synergistically activated expression of the atrial naturetic peptide gene (ANP) in transfected HeLa cells. GST‐pulldown and immunoprecipitation assay demonstrate that full‐length MEF2C protein is able to interact with dHAND in vitro and in vivo, just like MEF2A and bHLH transcription factors MyoD in skeletal muscle cells. In addition, electrophoretic mobility shift assays (EMSAs) demonstrate that MEF2C and dHAND do not influence each other's DNA binding activity. Using chromatin immunoprecipitation (ChIP) analysis in H9c2 cells we show that dHAND interact with MEF2C to form protein complex and bind A/T sequence in promoter of ANP. Taken together with previous observations, these results suggest the existence of large multiprotein transcriptional complex with core DNA binding proteins that physically interact with other transcriptional factors to form favorable conformation to potentiate transcription. © 2004 Wiley‐Liss, Inc.
ApcMin/+ mouse model of colon cancer: Gene expression profiling in tumors
Authors: Leclerc Daniel , Deng Liyuan , Trasler Jacquetta , Rozen Rima
Published: October 2004

The ApcMin/+ mouse is a popular animal model for studies of human colon cancer, but the molecular changes associated with neoplasia in this system have only been partially characterized. Our aim was to identify novel genes involved in tumorigenesis in this model. RNA from intestinal adenomas and from pre‐neoplastic small intestine were prepared from six ApcMin/+ mice. The tumor transcriptomes were analyzed with high‐density oligonucleotide microarrays representing ∼12,000 probe sets; we compared their profiles with those of matched pre‐neoplastic intestine. Stringent analysis revealed reproducible changes for 98 probe sets representing 90 genes, including novel observations regarding 50 genes whose involvement in this mouse model has never been reported. In addition to the expected changes in growth regulatory genes, the altered gene products could be assigned to four functional groupings that should enhance tumorigenesis: metabolic changes that would result in a high rate of glycolysis, alterations in enzymes involved in reactive oxygen species or carcinogen metabolism, cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A fifth group consisted of expression changes that might restrict tumor progression, suggesting that the adenomatous state reflects a balance of pro‐ and anti‐tumorigenic factors. Since many of the altered genes had not previously been reported to be involved in any tumorigenic processes, our observations provide a host of new candidates for potential modulation to prevent or treat intestinal neoplasia. Supplementary material for this article can be found at http://www.mrw.interscience.wiley.com/suppmat/0730‐2312/suppmat/v93.html. © 2004 Wiley‐Liss, Inc.
Aluminum decreases the glutathione regeneration by the inhibition of NADP‐isocitrate dehydrogenase in mitochondria
Authors: Murakami Keiko , Yoshino Masataka
Published: October 2004

Effect of aluminum on the NADPH supply and glutathione regeneration in mitochondria was analyzed. Reduced glutathione acted as a principal scavenger of reactive oxygen species in mitochondria. Aluminum inhibited the regeneration of glutathione from the oxidized form, and the effect was due to the inhibition of NADP‐isocitrate dehydrogenase the only enzyme supplying NADPH in mitochondria. In cytosol, aluminum inhibited the glutathione regeneration dependent on NADPH supply by malic enzyme and NADP‐isocitrate dehydrogenase, but did not affect the glucose 6‐phosphate dehydrogenase dependent glutathione formation. Aluminum can cause oxidative damage on cellular biological processes by inhibiting glutathione regeneration through the inhibition of NADPH supply in mitochondria, but only a little inhibitory effect on the glutathione generation in cytosol. © 2004 Wiley‐Liss, Inc.
Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells
Authors: Boland Genevieve M. , Perkins Geraldine , Hall David J. , Tuan Rocky S.
Published: October 2004

Multipotential adult mesenchymal stem cells (MSCs) are able to differentiate along several known lineages, and lineage commitment is tightly regulated through specific cellular mediators and interactions. Recent observations of a low/high bone‐mass phenotype in patients expressing a loss‐/gain‐of‐function mutation in LRP5, a coreceptor of the Wnt family of signaling molecules, suggest the importance of Wnt signaling in bone formation, possibly involving MSCs. To analyze the role of Wnt signaling in mesenchymal osteogenesis, we have profiled the expression of WNTs and their receptors, FRIZZLEDs (FZDs), and several secreted Wnt inhibitors, such as SFRPs, and examined the effect of Wnt 3a, as a representative canonical Wnt member, during MSC osteogenesis in vitro. WNT11, FZD6, SFRP2, and SFRP3 are upregulated during MSC osteogenesis, while WNT9A and FZD7 are downregulated. MSCs also respond to exogenous Wnt 3a, based on increased β‐catenin nuclearization and activation of a Wnt‐responsive promoter, and the magnitude of this response depends on the MSC differentiation state. Wnt 3a exposure inhibits MSC osteogenic differentiation, with decreased matrix mineralization and reduced alkaline phosphatase mRNA and activity. Wnt 3a treatment of fully osteogenically differentiated MSCs also suppresses osteoblastic marker gene expression. The Wnt 3a effect is accompanied by increased cell number, resulting from both increased proliferation and decreased apoptosis, particularly during expansion of undifferentiated MSCs. The osteo‐suppressive effects of Wnt 3a are fully reversible, i.e., treatment prior to osteogenic induction does not compromise subsequent MSC osteogenesis. The results also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects on MSCs, and that inhibition of canonical Wnt signaling using a dominant negative TCF1 enhances MSC osteogenesis. Interestingly, expression of Wnt 5a, a non‐canonical Wnt member, appeared to promote osteogenesis. Taken together, these findings suggest that canonical Wnt signaling functions in maintaining an undifferentiated, proliferating progenitor MSC population, whereas non‐canonical Wnts facilitate osteogenic differentiation. Release from canonical Wnt regulation is a prerequisite for MSC differentiation. Thus, loss‐/gain‐of‐function mutations of LRP5 would perturb Wnt signaling and depress/promote bone formation by affecting the progenitor cell pool. Elucidating Wnt regulation of MSC differentiation is important for their potential application in tissue regeneration. Published 2004 Wiley‐Liss, Inc.
Effects of low density lipoprotein receptor‐related protein‐1 on the expression of platelet‐derived growth factor β‐receptor in vitro
Authors: Wu Lihua , Arandjelovic Sanja , Gonias Steven L.
Published: October 2004

The low density lipoprotein receptor related protein‐1 (LRP‐1) is a cargo transport receptor that undergoes constitutive endocytosis and recycling. Platelet‐derived growth factor‐BB (PDGF‐BB) binds to LRP‐1 and may bridge LRP‐1 to PDGF receptors. Bridging of LRP‐1 to other receptors by bifunctional ligands may represent a general mechanism whereby LRP‐1 facilitates internalization of membrane proteins. The goal of this study was to determine whether LRP‐1 regulates cell‐surface levels of PDGF β‐receptor or PDGF β‐receptor degradation following treatment with PDGF‐BB. Unexpectedly, in both murine embryonic fibroblasts (MEFs) and HT 1080 fibrosarcoma cells, LRP‐1 expression was associated with increased levels of PDGF β‐receptor. In MEFs, the mechanism involved increased PDGF β‐receptor transcription and/or RNA stabilization. LRP‐1 expression was not associated with increased levels of PDGF β‐receptor in Chinese hamster ovary (CHO) cells, suggesting that cell context is important. The kinetics of PDGF β‐receptor phosphorylation, in response to PDGF‐BB, and the extent of degradation of PDGF β‐receptor were equivalent in LRP‐1‐expressing and ‐deficient MEFs. We conclude that PDGF β‐receptor expression and cell surface levels may be regulated by LRP‐1; however, this activity is cell type‐specific. LRP‐1 does not directly regulate PDGF β‐receptor phosphorylation or degradation in PDGF‐BB‐treated cells. © 2004 Wiley‐Liss, Inc.
Poly(ADP‐ribose) polymerase‐1: Association with nuclear lamins in rodent liver cells
Authors: Vidaković Melita , Grdović Nevena , Quesada Piera , Bode Jürgen , Poznanović Goran
Published: October 2004

The distribution of poly(ADP‐ribose) polymerase‐1 (PARP‐1) over different nuclear compartments was studied by nuclear fractionation procedures and Western analysis revealing a prominent role of the nuclear matrix. This structure is operationally defined by the solubility properties of the A‐ and B‐type lamins under defined experimental conditions. We consistently observed that most of the nuclear matrix‐associated PARP‐1 partitioned, in an active form, with the insoluble, lamin‐enriched protein fractions that were prepared by a variety of established biochemical procedures. These PARP‐1–protein interactions resisted salt extraction, disulfide reduction, RNase and DNase digestion. An inherent ability of PARP‐1 to reassemble with the lamins became evident after a cycle of solubilization/dialysis using either urea or Triton X‐100 and disulfide reduction, indicating that these interactions were dominated by hydrophobic forces. Together with in vivo crosslinking and co‐immunoprecipitation experiments our results show that the lamins are prominent PARP‐1‐binding partners which could contribute to the functional sequestration of the enzyme on the nuclear matrix. © 2004 Wiley‐Liss, Inc.