bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Molecular Structure and Catalytic Activity of Six‐Coordinate Chloro(hydrido)‐ and Dihydridoruthenium(II) and ‐osmium(II) Complexes with the Chiral Ligands PiPr2NH(Me)Ph, (S,S)‐Chiraphos and (S,S,)‐Diop
Authors: Schlünken Christoph , Esteruelas Miguel A. , Lahoz Fernando J. , Oro Luis A. , Werner Helmut
Published: April 2004

The five‐coordinate compounds [MHCl(CO)(PiPr3)2] (where 1a: M = Ru; 1b: M = Os) react with PiPr2R* [where R* = CH(Me)Ph] to give the octahedral complexes mer‐[MHCl(CO)(PiPr2R*)3] (6 and 7). The lability of the phosphane trans to the hydride is illustrated by the replacement reactions with CO, P(OMe)3 and C2(CO2Me)2, which afford the substitution products [MHCl(CO)(L)(PiPr2R*)2] (8−12) in high yields. The reactions of 1a and 1b with (S,S)‐Chiraphos and (S,S)‐Diop lead to one or two diastereoisomers of the chelate complexes [MHCl(CO)(PiPr3)(Chiraphos)] (15, 16) and [MHCl(CO)(PiPr3)(Diop)] (17, 18); the ratio of the diastereoisomers is dependent on the metal, the bidentate ligand and the reaction conditions. The racemate of [OsHCl(CO)(PiPr3)(dppe)] (14) was obtained from 1b and 1,2‐C2H4(PPh2)2 (dppe). The hydrido(tetrahydroboranato) compounds [MH(κ2‐H2BH2)(CO)(PiPr3)2] (where 2a: M = Ru; 2b: M = Os) also react with (S,S)‐Chiraphos and (S,S)‐Diop to give either the mononuclear, octahedral, chelate complexes 19−21 or, for M = Os and (S,S)‐Diop, the dinuclear compound [{OsH2(CO)(PiPr3)2}2(μ‐Diop)] (22). The molecular structure of 22 was determined crystallographically. Treatment of [OsH2Cl2(PiPr3)2] (23) with two equivalents of (S,S)‐Chiraphos afforded stepwise [OsH2Cl2(PiPr3)(Chiraphos)] (25) and, after reductive elimination of HCl and displacement of PiPr3, trans‐[OsHCl(Chiraphos)2] (24). Both 24 and [OsH2(Chiraphos)2] (27), which was prepared from 24 and NaBH4/MeOH, were transformed with HBF4 in diethyl ether into the dihydrogen complexes [OsCl(H2)(Chiraphos)2]BF4 (28) and [OsH(H2)(Chiraphos)2]BF4 (29) in excellent yields. The catalytic activity of the chloro(hydrido)‐ and dihydridometal derivatives in the asymmetric transfer hydrogenation of acetophenone with 2‐propanol was investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Intramolecular Nucleophilic Substitution in a C6F5 Moiety Assisted by Antimony
Authors: Shutov Pavel L. , Karlov Sergey S. , Harms Klaus , Tyurin Daniil A. , Sundermeyer Jörg , Lorberth Jörg , Zaitseva Galina S.
Published: April 2004

Antimony tris‐amides — (Et2N)3−nSb[N(C6F5)(2‐C5H4N)]n [n = 1 (3), 2 (4) or 3 (5)] — have been prepared by treatment of Sb(NEt2)3 (1) with stoichiometric amounts of (2‐C5H4N)(C6F5)NH (2). In contrast to amide 5, compounds 3 and 4 are unexpectedly unstable and react further to give the bis‐amido antimony fluorides [(2‐Et2N‐C6F4)(2‐C5H4N)N]Sb(F)[N(C2H5)2] (6) and [(2‐Et2N‐C6F4)(2‐C5H4N)N]Sb(F)[N(C6F5)(2‐C5H4N)] (7). The structure of 7 was confirmed by X‐ray diffraction studies. DFT calculations, which reproduce the principal features of compound 7’s geometry, have been used to explain the possible reaction pathway of this ortho‐directed metathetical fluoride‐amide exchange. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Day treatment group programme for eating disorders: reasons for drop‐out
Authors: Franzen Ute , Backmund Herbert , Gerlinghoff Monika
Published: April 2004

This study was designed to identify clinical variables and personality factors that could predict the completion or non‐completion of a day treatment group programme for patients with eating disorders. Patients (n = 125) were subdivided into those who had completed a 4‐month day treatment programme (n = 106) and those who had dropped out (n = 19). All the patients had been assessed with regard to eating psychopathology, general psychopathology and personality features at the beginning of the programme. At presentation, 50.4 per cent fulfilled DSM‐IV criteria for anorexia nervosa, 39.2 per cent for bulimia nervosa and 10.4 per cent for an eating disorder not otherwise specified. Non‐completion of therapy was associated with more severe bulimic symptoms, high levels of aggression and extraversion and low levels of inhibitedness. Assessment of these characteristics could be used to improve the therapy programme and to help those patients at increased risk of dropping out. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.
Permutation tests for factorially designed neuroimaging experiments
Authors: Suckling John , Bullmore Ed
Published: April 2004

Permutation methods for analysis of functional neuroimaging data acquired as factorially designed experiments are described and validated. The F ratio was estimated for main effects and interactions at each voxel in standard space. Critical values corresponding to probability thresholds were derived from a null distribution sampled by appropriate permutation of observations. Spatially informed, cluster‐level test statistics were generated by applying a preliminary probability threshold to the voxel F maps and then computing the sum of voxel statistics in each of the resulting three‐dimensional clusters, i.e., cluster “mass.” Using simulations comprising two between‐ or within‐subject factors each with two or three levels, contaminated by Gaussian and non‐normal noise, the voxel‐wise permutation test was compared to the standard parametric F test and to the performance of the spatially informed statistic using receiver operating characteristic (ROC) curves. Validity of the permutation‐testing algorithm and software is endorsed by almost identical performance of parametric and permutation tests of the voxel‐level F statistic. Permutation testing of suprathreshold voxel cluster mass, however, was found to provide consistently superior sensitivity to detect simulated signals than either of the voxel‐level tests. The methods are also illustrated by application to an experimental dataset designed to investigate effects of antidepressant drug treatment on brain activation by implicit sad facial affect perception in patients with major depression. Antidepressant drug effects in left amygdala and ventral striatum were detected by this software for an interaction between time (within‐subject factor) and group (between‐subject factor) in a representative two‐way factorial design. Hum. Brain Mapping 22:193–205, 2004. © 2004 Wiley‐Liss, Inc.
Hepatic transmethylation reactions in micropigs with alcoholic liver disease
Authors: Villanueva Jesus A. , Halsted Charles H.
Published: April 2004

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism, including increased levels of homocysteine and S-adenosylhomocysteine (SAH) and reduced levels of S-adenosylmethionine (SAM) and glutathione (GSH). The concept that abnormal methionine metabolism is involved in the pathogenesis of alcoholic liver disease was strengthened by our previous findings in a micropig model where combining dietary folate deficiency with chronic ethanol feeding produced maximal changes in these metabolites together with early onset of microscopic steatohepatitis and an eightfold increase in plasma aspartate aminotransferase. The goal of the present study was to determine potential mechanisms for abnormal levels of these methionine metabolites by analyzing the transcripts and activities of transmethylation enzymes in the livers of the same micropigs. Ethanol feeding or folate deficiency, separately or in combination, decreased transcript levels of methylenetetrahydrofolate reductase (MTHFR), methionine adenosyltransferase (MAT1A), glycine-N-methyltransferase (GNMT) and S-adenosylhomocysteine hydrolase (SAHH). Ethanol feeding alone reduced the activities of methionine synthase (MS) and MATIII and increased the activity of GNMT. Each diet, separately or in combination, decreased the activities of MTHFR and SAHH. In conclusion, the observed abnormal levels of methionine metabolites in this animal model of accelerated alcoholic liver injury can be ascribed to specific effects of ethanol with or without folate deficiency on the expressions and activities of hepatic enzymes that regulate transmethylation reactions. These novel effects on transmethylation reactions may be implicated in the pathogenesis of alcoholic liver disease. (Hepatology 2004;39:1303-1310.)
Screening in liver disease: Report of an AASLD clinical workshop
Authors: Adams Paul C. , Arthur Michael J. , Boyer Thomas D. , DeLeve Laurie D. , Di Bisceglie Adrian M. , Hall Mark , Levin Theodore R. , Provenzale Dawn , Seeff Leonard
Published: April 2004

This report summarizes an AASLD Clinical Workshop that was presented at Digestive Diseases Week 2003 on screening in liver diseases. As newer diagnostic tests become available, many liver diseases and complications of liver disease can be detected at an early asymptomatic stage. In many cases, early detection can lead to earlier treatment and an improved outcome. However, screening for liver diseases in asymptomatic persons has the potential for adverse consequences, including discrimination and stigmatization. The cost of screening programs is significant, and access to screening tests varies in different countries. Future screening programs require careful planning and implementation to balance the benefits, risks, and cost-effectiveness. This review outlines the concepts of screening and their application to a broad range of liver diseases. (Hepatology 2004;39:1204-1212.)
Down-regulation of the organic cation transporter 1 of rat liver in obstructive cholestasis
Authors: Denk Gerald U. , Soroka Carol J. , Mennone Albert , Koepsell Hermann , Beuers Ulrich , Boyer James L.
Published: April 2004

The liver plays a major role in biotransformation and elimination of various therapeutic agents and xenobiotics, many of which are organic cations and substrates of the organic cation transporter 1 (Oct1, Slc22a1). Oct1 is expressed at the basolateral membranes of hepatocytes and proximal renal tubules. Although Oct1 is the major uptake mechanism in hepatocytes for many pharmaceutical compounds, little is known about the effects of liver injury on this process. Our aim was to investigate the effects of obstructive cholestasis on Oct1 expression and function in liver and kidney. The effects of bile duct ligation (BDL) on Oct1 protein, messenger RNA (mRNA) expression, and tissue localization were determined in rat liver and kidney with Western analysis, real-time reverse transcriptase-mediated polymerase chain reaction (RT-PCR), and immunofluorescence. To assess Oct1 function, the model substrate tetraethylammonium ([14C]TEA) was administered intravenously to BDL and control rats and distribution of radioactivity was determined. Oct1 protein significantly decreased in cholestatic livers to 42.1 ± 17.7% (P < .001), 15.5 ± 4.7% (P < .05), and 8.6 ± 2.7% (P < .05) of controls after 3, 7, and 14 days, respectively, but not in kidneys. Hepatic Oct1 mRNA decreased to 77.2 ± 12.7%, 40.7 ± 8.1% (P < .05), and 50.3 ± 7.5% (P < .05) 3, 7, and 14 days after BDL, respectively. Tissue immunofluorescence corroborated these data. Hepatic accumulation of [14C]TEA in 14-day BDL rats was reduced to 29.6 ± 10.9% of controls (P < .0005). In conclusion, obstructive cholestasis down-regulates Oct1 and impairs Oct1-mediated uptake in rat liver, suggesting that hepatic uptake of small cationic drugs may be impaired in cholestatic liver injury. (Hepatology 2004;39:1382-1389.)
2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: Confocal and electron microscopic studies
Authors: Paku Sándor , Nagy Peter , Kopper László , Thorgeirsson Snorri S.
Published: April 2004

The 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) model is one of the most extensively studied experimental systems for oval cell proliferation and differentiation. We have previously described the oval cells as forming ductular structures surrounded by basement membrane, representing extensions of the canals of Hering. Herein we analyze the differentiation of oval cells into hepatocytes after varying degrees of liver damage induced by AAF. At a low dose of AAF, most oval cells synchronously differentiate into small hepatocytes by 6 days after the PH, resulting in complete restoration of the liver structure in 10 days. Higher doses of AAF delay the differentiation process and the new hepatocytes form foci, in contrast to what is observed at the low dose. Qualitatively, the differentiation process seems to be identical at the cellular level under both conditions. The transition from the expanding oval cell population into hepatocytes was correlated with the upregulation of hepatocyte nuclear factor 4 and the disappearance of the basement membrane. Also, the differentiation of oval cells into hepatocytes coincided with the loss of alpha-fetoprotein and OV-6 staining, and the replacement of the biliary cell-specific α6 integrin and connexin 43 with the hepatocyte-specific α1 integrin and connexin 32. In addition, bile canaliculi form between the new hepatocytes. In conclusion, these results indicate the rate of oval cell differentiation into hepatocytes is context dependent and suggest that, under favorable conditions, oval cells can complete this process much faster than previously appreciated. (Hepatology 2004;39:1353-1361.)
Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation
Authors: Radaeva Svetlana , Sun Rui , Pan Hong-na , Hong Feng , Gao Bin
Published: April 2004

The central role of T cell activation in hepatocellular injury has been well documented. In this article, we provide evidence suggesting that T cells may also play a protective role in liver disease by releasing interleukin-22 (IL-22), a recently identified T cell-derived cytokine whose biological significance is unclear. IL-22 messenger RNA and protein expression are significantly elevated in T cell-mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride-induced liver injury model. Activated CD3+ T cells are likely responsible for the production of IL-22 in the liver after injection of ConA. The IL-22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection. IL-22 blockade with a neutralizing antibody reduces signal transducer and activator of transcription factor 3 (STAT3) activation and worsens liver injury in T cell-mediated hepatitis, whereas injection of recombinant IL-22 attenuates such injury. In vitro treatment with recombinant IL-22 or overexpression of IL-22 promotes cell growth and survival in human hepatocellular carcinoma HepG2 cells. Stable overexpression of IL-22 in HepG2 cells constitutively activates STAT3 and induces expression of a variety of antiapoptotic (e.g., Bcl-2, Bcl-xL, Mcl-1) and mitogenic (e.g., c-myc, cyclin D1, Rb2, CDK4) proteins. Blocking STAT3 activation abolishes the antiapoptotic and mitogenic actions of IL-22 in hepatic cells. In conclusion, the T cell-derived cytokine IL-22 is a survival factor for hepatocytes; this suggests that T cell activation may also prevent and repair liver injury by releasing hepatoprotective cytokine IL-22 in addition to its previously documented central role in hepatocellular injury. (Hepatology 2004;39:1332-1342.)
In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD)
Authors: Sauer Igor M. , Goetz Max , Steffen Ingo , Walter Gesa , Kehr Daniel C. , Schwartlander Ruth , Hwang Yoon J. , Pascher Andreas , Gerlach Joerg C. , Neuhaus Peter
Published: April 2004

The detoxification capacities of single-pass albumin dialysis (SPAD), the molecular adsorbents recirculation system, (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) were compared in vitro. In each experiment 4,100 mL of toxin-loaded human plasma was processed for 6.5 hours. MARS treatment (n = 6) was undertaken in combination with CVVHDF. For SPAD (n = 6) and CVVHDF (n = 6) a high-flux hollow fiber hemodiafilter (identical to the MARS filter) was used. Levels of ammonia, urea, creatinine, bilirubin, and bile acids were determined. Concentrations before and after application of detoxification procedures were expressed as differences and were compared using the Kruskal-Wallis test. Post hoc comparisons for pairs of groups were adjusted according to Bonferroni-Holm. Time, group, and interaction effects were tested using the nonparametric ANOVA model for repeated measurements. SPAD and CVVHDF induced a significantly greater reduction of ammonia levels than MARS. No significant differences were found among SPAD, MARS, and CVVHDF with respect to other water-soluble substances. SPAD induced a significantly greater reduction in bilirubin levels than MARS. Reductions in bile acid levels were similar for SPAD and MARS. When operating MARS in continuous veno-venous hemodialysis mode, as recommended by the manufacturer, no significant differences in the removal of bilirubin, bile acids, urea, and creatinine were found. However, MARS in continuous veno-venous hemodialysis mode was significantly less efficient in removing ammonia than MARS in CVVHDF mode. In conclusion, the detoxification capacity of SPAD is similar to or even greater than that of MARS. (Hepatology 2004;39:1408-1414.)
Short-term interferon-alfa therapy for acute hepatitis C: A randomized controlled trial
Authors: Nomura Hideyuki , Sou Suketo , Tanimoto Hironori , Nagahama Takashi , Kimura Yoichi , Hayashi Jun , Ishibashi Hiromi , Kashiwagi Seizaburo
Published: April 2004

Acute hepatitis C often progresses to chronic infection. We undertook a randomized controlled trial to determine whether short-term therapy with interferon (IFN) during acute hepatitis C is effective in preventing the development of chronic hepatitis. Thirty patients with acute hepatitis C were randomized into 1 of 2 treatment groups. IFN therapy was initiated 8 weeks after the onset of acute hepatitis in the early-intervention group and after 1 year of observation in the late-intervention group. Short-term therapy consisted of natural IFN-alfa (6 million units) administered on consecutive days for a period of 4 weeks. Any signs of recrudescence of disease were immediately followed by interval IFN therapy (3 times weekly for 20 weeks). In the early-intervention group, short-term therapy was associated with a sustained virological response in 13 of 15 patients (87%). Follow-up treatment was associated with a sustained virological response in both of the remaining 2 patients (100%). The sustained virological response rate was significantly higher in the early-intervention group (87%, 13 of 15 patients after short-term therapy alone, and 100%, 15 of 15 patients after short-term with or without follow-up therapy) than in the late-intervention group (40%, 6 of 15 patients after short-term therapy alone, and 53%, 8 of 15 patients after short-term therapy with or without follow-up therapy, P = .021 and P = .006, respectively). In conclusion, short-term (4 weeks) IFN treatment of patients with acute hepatitis C may be associated with satisfactory results, if initiated at an early stage of the disease. (Hepatology 2004;39:1213-1219.)
Cytokines increase CRE binding but decrease CRE-mediated reporter activity in rat hepatocytes by increasing c-Jun
Authors: Zhang Baochun , Liu Shubing , Perpetua Michele D. , Walker William H. , Harbrecht Brian G.
Published: April 2004

The cyclic AMP response element (CRE) has been implicated in the regulation of the expression of many genes and cellular processes important in hepatocyte function. CRE sites exist in the promoter regions of several genes expressed during inflammation. Numerous studies on the role of CRE in hepatocyte gene expression have been performed in resting hepatocytes, but the role of CRE during inflammation is unknown. To evaluate the regulation of CRE-mediated transcription during sepsis, cultured hepatocytes were exposed to proinflammatory cytokines and lipopolysaccharide (LPS) was injected into rats. Nuclear proteins were collected and CRE binding activity measured by electromobility shift assay (EMSA) using a consensus CRE oligonucleotide. CRE binding activity was increased in vitro by cytokines and in vivo by LPS administration but CRE-dependent reporter activity was decreased by cytokine stimulation. A c-jun N-terminal kinase (JNK) inhibitor reversed the cytokine-induced increase in CRE binding and increased CRE-dependent reporter activity. Supershift assays indicated that cyclic AMP response element binding protein (CREB) and c-Jun proteins were included in the CRE binding complex. CREB induced and c-Jun suppressed reporter activity using a CRE-dependent construct transfected into cultured primary hepatocytes. In conclusion, these data demonstrate that proinflammatory cytokines regulate CRE binding and activity in cultured hepatocytes and suggest that sepsis-induced changes in CRE binding may participate in the cellular response to inflammation. (Hepatology 2004;39:1343-1352.)
An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice
Authors: Pei Zifei , Chu Liang , Zou Weiguo , Zhang Zilai , Qiu Songbo , Qi Rong , Gu Jinfa , Qian Cheng , Liu Xinyuan
Published: April 2004

Hepatocellular carcinoma (HCC) displays a high resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. To increase sensitivity of HCC cells to TRAIL, we have constructed an oncolytic adenoviral vector (ZD55) and used this vector to deliver second mitochondria-derived activator of caspases (Smac) and TRAIL genes (ZD55-Smac and ZD55-TRAIL, respectively) into HCC cells. Our data showed that human HCC cells express high levels of inhibitor of apoptosis proteins (IAPs). Transfected HCC cells expressing exogenous X-linked IAPs (XIAPs) displayed more resistance to TRAIL. The expression of Smac led to rapid and potent activation of apoptosis in HCC cells after infection with ZD55-Smac. The activation of caspases and induction of apoptosis could be enhanced further through coinfection with ZD55-TRAIL. The combined treatment of ZD55-Smac and ZD55-TRAIL resulted in significant reduction of XIAP expression levels. In addition, our in vivo data in mice showed only a partial response in the established tumor treated either by ZD55-Smac or ZD55-TRAIL alone. By contrast, complete tumor regression was observed by combination of ZD55-Smac and ZD55-TRAIL in all treated animals. This strong antitumoral activity achieved by this combination was due to a dramatic induction of tumor cell apoptosis in the treated tumors. In conclusion, our data indicate that Smac antagonizes the IAPs in HCC tumor cells and enhances tumor cell death induced by TRAIL in the oncolytic adenoviral vector. The combination of Smac and TRAIL delivered by way of the oncolytic adenoviral vector would provide a useful strategy for therapy of HCC and might also be applied to other IAPs abundant in cancers. (Hepatology 2004;39:1371-1381.)
Design, Synthesis, and Characterization of Photolabeling Probes for the Study of the Mechanisms of the Antiviral Effects of Ribavirin
Authors: Wu Qiongyou , Qu Fanqi , Wan Jinqiao , Zhu Xun , Xia Yi , Peng Ling
Published: April 2004

Ribavirin, the only small molecule available so far for treating hepatitis‐C‐virus infection, was recently used in an emergency context to treat patients with severe acute respiratory syndrome (SARS) in the early stages of the disease. To study the mechanisms responsible for the antiviral effects of ribavirin by using a photolabeling approach, we designed, synthesized, and characterized the azidotriazole nucleosides 1 and 2 as photolabeling probes of ribavirin. These probes were synthesized either by performing nucleophilic substitution of the corresponding bromotriazole nucleoside with NaN3 (Scheme 2) or by directly coupling the azidotriazole with the protected ribose sugar (Scheme 4). The azidotriazole nucleosides 1 and 2 showed a fast, clear‐cut photochemical reaction, which suggests that they are promising candidates for use in photolabeling studies.
Spectroscopic Properties of 4‐Pyridoxic Acid as a Function of pH and Solvent
Authors: Bueno Claudia , Guerrero Juan , Encinas María Victoria
Published: April 2004

The photophysical properties and acid/base equilibria of 4‐pyridoxic acid (=3‐hydroxy‐5‐(hydroxymethyl)‐2‐methylpyridine‐4‐carboxylic acid), the final product of the catabolism of vitamin B6, have been studied in aqueous solutions. The ground state of 4‐pyridoxic acid exhibits the different protonated forms A–D in the range of H0=−6 to pH 11.5. HMQC‐ and HMBC‐NMR Studies allowed the pH‐dependent assignment of the different C‐atoms, and the evaluation of the deprotonation sequence. The 3‐OH group in the ground state has a ‘pKa’ of H0=−0.64, which is much lower than that found for other vitamin B6 related compounds. The pKa value of the 4‐COOH group is 5.4. Fluorescence studies showed that the same species exist at the lowest excited singlet state, but in different pH ranges. The 3‐OH group is four pH units more acidic in the lowest excited singlet state than in the ground state. Excitation spectra and emission decays in the pH range of 8 to 11.5 indicate that the pyridine N‐atom is more basic in the excited singlet state than in the ground state. The emission spectra are red‐shifted in protic solvents, in agreement with an intramolecular H‐bond between the ionized 3‐OH group and the nonionized 4‐COOH group.
Novel Diterpenoids from Salvia dugesii
Authors: Xu Gang , Peng Liyan , Niu Xuemei , Zhao Qinshi , Li Rongtao , Sun Handong
Published: April 2004

Two novel rearranged clerodane diterpenoids, dugesin A (1) and dugesin B (2), were isolated from the aerial parts of Salvia dugesii, together with five known clerodane diterpenoids: isosalvipuberulin (3), salvipuberulin (4), tilifodiolide (5), salvifolin (6), and salvifaricin (7). Their structures were elucidated on the basis of different spectroscopic techniques. The isolation and identification of these compounds are significant from both biosynthetisis and chemotaxonomy points of view.
Synthesis and Cytotoxic and Antiplatelet Activities of Dibenzofuran‐ and Carbazole‐Substituted Oximes
Authors: Wang Tai‐Chi , Chen I‐Li , Kuo Daih‐Huang , Liao Chang‐Hui
Published: April 2004

The dibenzofuran‐ and carbazole‐substituted oximes or methyloximes 5–10 were prepared and evaluated for their cytotoxic and antiplatelet activities. These compounds were synthesized via alkylation of dibenzofuran‐2‐ol or 9H‐carbazol‐2‐ol with α‐halocarbonyl reagents, followed by reaction with NH2OH or NH2OMe (Scheme). A preliminary anticancer assay indicated that the oxime‐type dibenzofuran derivatives 5 and 7a–d are active, while the corresponding oxime ethers 9b and 9c are inactive at the same concentration. Therefore, a H‐bond‐donating group seems to be crucial for cytotoxicity. Among the compounds tested, 2‐[(dibenzo[b,d]furan‐2‐yl)oxy]‐1‐(4‐methoxyphenyl)ethan‐1‐one O‐methyloxime (9c) exhibited potent inhibitory activity against platelet aggregation induced by arachidonic acid, with an IC50 value of 14.87 μM, without being cytotoxic at a concentration of 100 μM.
Binding affinity prediction with different force fields: Examination of the linear interaction energy method
Authors: Almlöf Martin , Brandsdal BjØrn O. , Åqvist Johan
Published: April 2004

A systematic study of the linear interaction energy (LIE) method and the possible dependence of its parameterization on the force field and system (receptor binding site) is reported. We have calculated the binding free energy for nine different ligands in complex with P450cam using three different force fields (Amber95, Gromos87, and OPLS‐AA). The results from these LIE calculations using our earlier parameterization give relative free energies of binding that agree remarkably well with the experimental data. However, the absolute energies are too positive for all three force fields, and it is clear that an additional constant term (γ) is required in this case. Out of five examined LIE models, the same one emerges as the best for all three force fields, and this, in fact, corresponds to our earlier one apart from the addition of the constant γ, which is almost identical for the three force fields. Thus, the present free energy calculations clearly indicate that the coefficients of the LIE method are independent of the force field used. Their relation to solvation free energies is also demonstrated. The only free parameter of the best model is γ, which is found to depend on the hydrophobicity of the binding site. We also attempt to quantify the binding site hydrophobicity of four different proteins which shows that the ordering of γ's for these sites reflects the fraction of hydrophobic surface area. © 2004 Wiley Periodicals, Inc. J Comput Chem 10: 1242–1254, 2004
Regional hydrodynamic gene delivery to the rat liver with physiological volumes of DNA solution
Authors: Zhang Xiaohong , Dong Xuebin , Sawyer Greta J. , Collins Louise , Fabre John W.
Published: April 2004

Background

The major barrier to the clinical application of hydrodynamic gene delivery to the liver is the large volume of fluid required using standard protocols. Regional hydrodynamic gene delivery via branches of the portal vein has not previously been reported, and we have evaluated this approach in a rat model.

Methods

The pGL3 plasmid with the luciferase reporter gene was used at 50 µg/ml in isotonic solutions, and was administered with a syringe pump for precise control of the hydrodynamic conditions evaluated. Gene expression was individually measured in six anatomically distinct liver lobes. The effect of systemic chloroquine to promote endocytic escape and a (Lys)16‐containing peptide to condense the DNA into ∼100‐nm nanoparticles was also evaluated.

Results

Hydrodynamic conditions for excellent gene delivery were obtained by using 3‐ml volumes (∼12 ml/kg) of isotonic DNA solution delivered at 24 ml/min to the right lateral lobe (∼20% of the liver mass). Under these conditions, >95% of gene delivery usually occurred in the targeted right lateral lobe. Outflow obstruction was essential for gene delivery, both at optimal and at very low levels of hydrodynamic gene delivery. The use of systemic chloroquine to promote endocytic escape did not augment hydrodynamic gene delivery, while condensation of DNA in non‐ionic isotonic solutions (5% dextrose) to nanoparticles of ∼100 nm completely abolished gene delivery.

Conclusions

Regional hydrodynamic gene delivery via a branch of the portal vein offers a physiological model of liver gene therapy, for experimental and clinical application. Copyright © 2004 John Wiley & Sons, Ltd.
On the interval number of special graphs
Authors: Balogh József , Ochem Pascal , Pluhár András
Published: April 2004

The interval number of a graph G is the least natural number t such that G is the intersection graph of sets, each of which is the union of at most t intervals, denoted by i(G). Griggs and West showed that $i(G)\le \lceil {1\over 2} (d+1)\rceil $. We describe the extremal graphs for that inequality when d is even. For three special perfect graph classes we give bounds on the interval number in terms of the independence number. Finally, we show that a graph needs to contain large complete bipartite induced subgraphs in order to have interval number larger than the random graph on the same number of vertices. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 241–253, 2004
High risk factors of hostage barricade incidents in a Japanese sample
Authors: Yokota Kaeko , Iwami Hirokazu , Watanabe Kazumi , Fujita Goro , Watanabe Shoichi
Published: April 2004

Hostage taking incidents in which the police besiege a particular location are known as hostage barricade incidents. The first aim of the present article was to examine the process of risk assessment in hostage incidents, using a group of police officers as the sample. The second aim was to identify the risk factors involved in hostage incidents and examine the degree of concordance between the risk as assessed by the police officers and the figures obtained from the analysis of actual hostage barricade incidents. For the purpose of this study, a survey was carried out across Japan, and 45 police officers responsible for hostage negotiation responded to the questionnaires. Additionally, a sample of 116 actual hostage barricade incidents that occurred in Japan from 1970 to 2002 was utilised to examine the high risk factors involved in such cases. As per the results, a majority of the police officers (73.3%), in response to an open‐ended question, indicated that the highly excited state of the hostage takers was dangerous for the hostages. Moreover, it was demonstrated in all 116 incidents that several factors such as ‘a long siege’ tended to increase the risk of deaths, though this was very rare (n = 4). On the other hand, the proportion of injuries to the hostages was high in expressive situations such as domestic situations or suicide attempt scenarios. On the whole, the results obtained from the analyses of actual incidents were consistent with those obtained from the police officers' risk assessment in many respects. However, the correlation between the degree of risk as assessed by the police officers and the actual rate of deaths/injuries to the hostages was very low. Copyright © 2004 John Wiley & Sons, Ltd.
Limited long‐term naive CD4+ T cell reconstitution in patients experiencing viral load rebounds during HAART
Authors: Choremi‐Papadopoulou H. , Tsalimalma K. , Dafni U. , Dimitracopoulou A. , Kordossis T.
Published: April 2004

Long‐term (3.5 years) immune reconstitution in relation to viral load response was determined. Plasma HIV‐1 RNA was suppressed in 40 patients (full responders) up to 42 months, and 17 patients achieved partial response. The measurements of CD4+ and CD8+ T lymphocyte subsets (CD45RA, CD45RACD62L, CD45RO, CD28, CD38) were carried out by flow cytometry. Full responders had a significant increase of CD4+ and all CD4+ T subsets both up to 6 and from 6 to 42 months, while the increase for partial responders was only up to 6 months. By 6 months, higher slopes were observed in full versus partial responders in the % of CD28 on CD4+ and the % of CD4+ memory subset and in both naïve and memory CD4+ subsets from 6 to 42 months. The percentage of CD8+ and its subsets was decreased significantly in full responders both up to 6 and from 6 to 42 months (except for an increase in the CD8+CD45RA+ CD62L+ cells), while in partial responders this decrease was only up to 6 months. Lower slopes were observed in full versus partial responders from 6 to 42 months in the percentages of CD8+, CD8+CD45RO+, CD8+CD28−, and CD8+CD38+ T cells. In conclusion, full responders have a stronger long‐term naive CD4+ T cell subset reconstitution than partial responders. J. Med. Virol. 73:235–243, 2004. © 2004 Wiley‐Liss, Inc.
A two decade survey of respiratory adenovirus in Taiwan: The reemergence of adenovirus types 7 and 4
Authors: Lin Kuei‐Hsiang , Lin Yung‐Cheng , Chen Hsiu‐Lin , Ke Guan‐Ming , Chiang Chi‐Jung , Hwang Kao‐Pin , Chu Pei‐Yu , Lin Jih‐Hui , Liu Ding‐Ping , Chen Hour‐Young
Published: April 2004

From November 1999 to December 2001, three outbreaks of adenovirus (Ad) respiratory infection occurred in southern Taiwan. To determine the circulating serotypes and molecular epidemiology, a total of 524 virus strains were randomly selected from 1,064 strains isolated from 1981 to 2001, and were studied using restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR)‐RFLP. The major subgenus found was subgenus B (45%), followed by subgenus E (29%) and subgenus C (25%). Ad3 and Ad7 were the major types found during the 1st outbreak, which occurred from November 1999 to March 2000, while Ad4 was found mainly during the 2nd and 3rd outbreaks in October 2000 and September 2001, respectively. Both Ad7 and Ad4 were reemerged serotypes, whereas Ad3 was consistently isolated during the survey, although it declined drastically from 36 to 2% in 2001. Genotype analysis in this study showed that the only strain of Ad7 found in 1983 was Ad7a, but all randomly selected strains of Ad7 isolated during 1999–2000 were Ad7b. The clinical features of 217 patients were analyzed during the 1999–2000 outbreaks. About 79% of the total cases were less than 7 years old. The ratio of male to female was 2:1. Severe infections, such as pneumonia and acute bronchitis, accounted for nearly half of the cases (43%). These results show the reemergence and changing of serotypes, the clinical association of respiratory adenovirus infections, and the molecular epidemiology of Ad7 genotypes in Taiwan during the past two decades. J. Med. Virol. 73:274–279, 2004. © 2004 Wiley‐Liss, Inc.
Production of interferon gamma in respiratory syncytial virus infection of humans is not associated with interleukins 12 and 18
Authors: Garofalo Roberto P. , Hintz Karen H. , Hill Vanessa , Ogra Pearay L. , Welliver Robert C.
Published: April 2004

In order to understand early events in the immune response to respiratory syncytial virus (RSV) infection, we studied the presence of various chemokines and cytokines in respiratory secretions of human infants with RSV infection. Interferon gamma (IFNγ) was present in 30/39 (76.9%) subjects tested, but the IFNγ‐inducing cytokines interleukin (IL)12 and IL18 were detectable in 6/40 (15%) and 11/38 (28.9%) subjects, respectively. Quantities of IL12 and IL18 did not correlate with those of IFNγ. IL18, but neither IFNγ nor IL12 was found in significantly greater concentrations in subjects with mild, nonhypoxic forms of bronchiolitis than in those with upper respiratory illness alone or hypoxic bronchiolitis. The findings suggest that IFNγ may be induced independently of the activities of IL12 and IL18 during RSV infection. Immune responses characterized by relatively greater release of IL18 may be associated with milder forms of bronchiolitis. J. Med. Virol. 73:289–294, 2004. © 2004 Wiley‐Liss, Inc.
Novel method for quantification of brain cell swelling in rat hippocampal slices
Authors: Nakajima Ryuichi , Nakamura Takeshi , Ogawa Miyuki , Miyakawa Hiroyoshi , Kudo Yoshihisa
Published: April 2004

We have developed a novel device for the quantification of edematous morphology changes in acute brain slices. We can also carry out real‐time monitoring of detailed hippocampal cells. The device we developed is based on infrared differential interference contrast microscopy (IR‐DIC) and a custom‐made real‐time computerized image‐analysis system for quantification of the morphological dynamics of cells in slice preparations. We applied the coefficient of variation (CV) of light intensity in IR‐DIC images to evaluate the change in morphological dynamics. We examined three kinds of edema in the CA1 region of rat hippocampal acute slices under conditions of hypotonic, strong excitation, and experimental ischemia, together with field excitatory postsynaptic potential (fEPSP) recording from radiatum in CA1 the region. There were notable close relationships among the edema formations, the light transmittance, the extent of changes in CV, and features of fEPSP during the three different insults. The present results indicate that CV is a reliable quantification index for edema formation in brain tissue and confirm that applying CV for the analysis in addition to the light transmittance analysis presents additional important information on brain tissue swelling. © 2004 Wiley‐Liss, Inc.
Cytokine‐induced cell death in human oligodendroglial cell lines: I. Synergistic effects of IFN‐γ and TNF‐α on apoptosis
Authors: Buntinx Mieke , Moreels Marjan , Vandenabeele Frank , Lambrichts Ivo , Raus Jef , Steels Paul , Stinissen Piet , Ameloot Marcel
Published: April 2004

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Myelin and oligodendrocytes are considered the major targets of injury caused by a cell‐mediated immune response. There is circumstantial evidence that proinflammatory cytokines like tumor necrosis factor α (TNF‐α) and interferon γ (IFN‐γ) could have disease‐promoting roles in multiple sclerosis (MS). In the present study, the cytotoxic effects of IFN‐γ and TNF‐α on the human oligodendroglial cell lines human oligodendroglioma (HOG) and MO3.13 were analyzed. When the oligodendroglial cell lines were cultured in the presence of IFN‐γ or TNF‐α, apoptotic cell death was observed in both cell lines after >24 hr incubation. Apoptosis was evidenced by a decrease in cell viability, apoptotic changes in cell and nucleus morphology, and disruption of the membrane asymmetry. Our data show that TNF‐α and IFN‐γ induce apoptosis in a dose‐dependent fashion in both oligodendroglial cell lines and that their synergistic effect results in enhanced cell death. Understanding the regulation of cell death pathways in oligodendrocytes is critical for protecting myelin‐producing cells and their associated axons during injury in patients with MS. © 2004 Wiley‐Liss, Inc.
Influence of Monomer Structure on the Propagation Kinetics of Acrylate and Methacrylate Homopolymerizations Studied via PLP‐SEC in Fluid CO2
Authors: Beuermann Sabine , Buback Michael , El Rezzi Véronique , Jürgens Michael , Nelke Dorit
Published: April 2004

Summary: Propagation kinetics of free‐radical homopolymerizations of methyl acrylate, dodecyl acrylate, butyl methacrylate, dodecyl methacrylate, glycidyl methacrylate, cyclohexyl methacrylate, and isobornyl methacrylate in solutions containing 40 wt.‐% CO2 were studied applying the PLP‐SEC technique. The obtained apparent propagation rate coefficients, kp,app, are by up to 40% below the associated bulk kp values. This reduction is assigned to a lowering of local monomer concentration, cM,loc, at the site of the free‐radical chain end rather than to a decrease of the actual propagation rate coefficient. With the alkyl (meth)acrylates, intersegmental interactions between polar groups of the same polymer molecule are responsible for deviations of cM,loc from the analytical overall monomer concentration, cM,a. Increasing size of the flexible alkyl ester group reduces the differences between cM,loc and cM,a due to shielding effects. Methacrylates with cyclic ester groups do not follow this trend. In case of isobornyl methacrylate, which polymerizes to a rigid material with large side groups, relative size of monomer and CO2 matters and reduces cM,loc significantly below cM,a.

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Lack of attribute searchability: Some thoughts
Authors: Mittal Banwari
Published: April 2004

Established theory about the searchability of product attributes has advanced a tripartite classification of product attributes and, correspondingly, a three‐pronged view of consumer evaluation procedures. Using this theory as a springboard, this article takes a closer look at the procedures consumers seem to utilize for evaluation of products that vary in their attribute searchability. Reflecting on current theory and practice, the consumer is construed to employ evaluation procedures different from those indicated by the product‐attribute typology. This is so both because consumers view the attributes differently and because they rely on biased heuristics, as might suit their expertise and involvement. To capture these consumer assessment dynamics, propositions are advanced and empirical methods to test them are suggested. © 2004 Wiley Periodicals, Inc.
Entropic structure of multicomponent reactive flows with partial equilibrium reduced chemistry
Authors: Giovangigli Vincent , Massot Marc
Published: April 2004

In this paper, we investigate the system of equations modelling multicomponent reactive flows with detailed transport and complex chemistry in the limit of partial equilibrium. The reduced system is obtained using a projection step compatible with the chemical entropy production. The reduced multicomponent transport and convection fluxes are shown to be compatible with the mathematical entropy thus providing a symmetric form as well as normal forms for the reduced system. This yields global existence and asymptotic stability around constant equilibrium states for the Cauchy problem on the partial equilibrium manifold in all space dimensions. Copyright © 2004 John Wiley & Sons, Ltd.
Attractor of dissipative radially symmetric Zakharov equations outside a ball
Authors: Li Yongsheng , Guo Boling
Published: April 2004

In this paper the authors study the long time behaviour of the radially symmetric solutions to the damped Zakharov equations on an exterior domain outside a ball and prove the existence of global attractors. Copyright © 2004 John Wiley & Sons, Ltd.
Sonic and kinetic phase transitions with applications to Chapman–Jouguet deflagrations
Authors: Colombo Rinaldo M. , Corli Andrea
Published: April 2004

We consider an n × n system of hyperbolic conservation laws and focus on the case of strongly underdetermined sonic phase boundaries. We propose a Riemann solver that singles out solutions uniquely. This Riemann solver has two features: it selects phase boundaries by means of an exterior function and it allows compound waves. Then we prove the global existence of weak solutions to the Cauchy problem. Applications to Chapman–Jouguet deflagrations are given. Copyright © 2004 John Wiley & Sons, Ltd.
Delta and singular delta locus for one‐dimensional systems of conservation laws
Authors: Nedeljkov Marko
Published: April 2004

This work gives a condition for existence of singular and delta shock wave solutions to Riemann problem for 2×2 systems of conservation laws. For a fixed left‐hand side value of Riemann data, the condition obtained in the paper describes a set of possible right‐hand side values. The procedure is similar to the standard one of finding the Hugoniot locus. Fluxes of the considered systems are globally Lipschitz with respect to one of the dependent variables. The association in a Colombeau‐type algebra is used as a solution concept. Copyright © 2004 John Wiley &Sons, Ltd.
Novel structure of an arrayed‐waveguide grating multiplexer with flat spectral response
Authors: Lee Tsung‐Hsin , Tu Kun‐Hung , Lee Ching‐Ting
Published: April 2004

A novel structure of arrayed‐waveguide grating (AWG) multiplexers with a graded‐index free‐propagation region (FPR) used to increase the wavelength pass band is presented. The 1‐dB and 3‐dB wavelength pass bands increase with the increase of the graded‐index FPR length. Flat and broadened spectral responses are obtained by using this novel structure. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 444–445, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20165
Isolated magnetic dipole antenna: Application to GPS
Authors: Rowson Sebastian , Poilasne Gregory , Desclos Laurent
Published: April 2004

An electrically small, low‐profile, antenna structure suitable for mobile devices is presented. An example of GPS implementation inside a cellular phone shows high antenna efficiency and integration flexibility. High isolation is shown by little detuning from various phone holding positions and high out of band rejection. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 449–451, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20167
A K‐band suspended microstripline‐fed linear tapered slot antenna and its E‐plane arrays
Authors: Wu Chen
Published: April 2004

A suspended microstripline‐fed linear tapered slot antenna element and its E‐plane linear arrays are presented in this paper. The element is studied and designed using the finite‐difference time‐domain (FDTD) method. The simulated results show that the element has a good antenna performance from 17 to 24 GHz. To build the E‐plane arrays, a unique five‐piece assembled structure which guarantees a uniform air‐filled thin substrate in the suspended microstrip line parallel feed‐network, has been developed. Four E‐plane arrays with different numbers of elements (4, 8, 16, and 32) are fabricated and their antenna gains and patterns are examined experimentally. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 451–455, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20168