bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Syntheses, Biological Evaluation, and Docking Studies of 2‐Substituted 5‐Methylsulfonyl‐1‐Phenyl‐1H‐Indoles: Potent and Selective in vitro Cyclooxygenase‐2 Inhibitors
Authors: Cruz‐López Olga , Díaz‐Mochón Juan José , Campos Joaquín M. , Entrena Antonio , Núñez María T. , Labeaga Luis , Orjales Aurelio , Gallo Miguel A. , Espinosa Antonio
Published: November 2006

Four series of 5‐methylsulfonyl‐1‐phenyl‐1H‐indole‐2‐carboxylic acid alkyl esters (family A), ‐2‐carbonitriles (family B), ‐2‐carboxamides (family C), and 2‐benzoyl‐5‐methylsulfonyl‐1‐phenyl‐1H‐indoles (family D) were prepared and evaluated for their ability to inhibit purified cyclooxygenase‐2 (COX‐2) and cyclooxygenase‐1 (COX‐1). Family D compounds have the best COX‐1/COX‐2 inhibition ratios and potencies. According to docking studies, these molecules appear to bind the COX‐2 binding site differently than indomethacin, with the insertion of the substituent at the 2‐position in the hydrophobic pocket of the enzyme and the 1‐position phenyl ring in the trifluoromethyl zone. Among the group of compounds evaluated, 2‐(4‐chlorobenzoyl)‐1‐(4‐chlorophenyl)‐5‐methylsulfonyl‐1H‐indole and 2‐(4‐chlorophenyl)‐5‐methylsulfonyl‐1‐(4‐trifluoromethylphenyl)‐1H‐indole emerged as the most potent (respective IC50 values: 46 and 43 nM), and selective (respective selectivity indexes: >2163 and >2331) COX‐2 inhibitors.
Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases
Authors: DiLuna Michael L. , King Joseph T. , Knisely Jonathan P. S. , Chiang Veronica L.
Published: November 2006

BACKGROUND.

Little is understood about the factors that influence survival in patients who undergo gamma‐knife stereotactic radiosurgery (SRS) for brain metastases.

METHODS.

Demographic, disease, treatment, and survival data on 334 patients with intracranial metastases who underwent initial SRS from 1998 to 2004 were abstracted from treatment records and from the Connecticut Tumor Registry. Multivariate survival analysis was used to identify factors that independently affected survival.

RESULTS.

The median age of the patient population was 57.3 years. The median number of lesions treated in a single session was 2 (range, 1–36 lesions treated). The most common tumor histologies were nonsmall cell lung carcinoma (36%), breast cancer (16%), and melanoma (16%). Three hundred patients (90%) had confirmed deaths; the median survival after SRS was 8.1 months. Survival was significantly better in patients who had from 1 to 3 metastases (median, 8.5 months) compared with patients who had ≥4 metastases (median, 6.3 months; hazard ratio [HR], 0.65; P = .003). In the subgroup of patients who had from 1 to 3 metastases, systemic control (HR, 0.49; P < .001), breast cancer (HR, 0.57; P = .003), and total tumor volume < 5 cc (HR, 0.65; P = .002) were associated independently with increased survival, and esophageal cancer (HR, 2.36; P = .042) was associated with decreased survival. In the subgroup of patients who had ≥4 metastases, only age <45 years was associated independently with increased survival (HR, 0.39; P = .006); and melanoma (HR, 2.32; P = .008) and the receipt chemotherapy (HR, 2.59; P = .077) were associated with decreased survival. Sex, race, metastases location, whole‐brain radiation, and cranial surgery had no independent associations with altered survival.

CONCLUSIONS.

The data from this study suggested that different factors affected survival in patients who had from 1 to 3 metastases and patients who had ≥4 metastases. Further research into this area may clarify causes for this discrepancy and improve prognostication. Cancer 2007. © 2006 American Cancer Society.
Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome
Authors: Kantarjian Hagop M. , O'Brien Susan , Shan Jianqin , Aribi Ahmed , Garcia‐Manero Guillermo , Jabbour Elias , Ravandi Farhad , Cortes Jorge , Davisson Jan , Issa Jean‐Pierre
Published: November 2006

BACKGROUND.

Therapy for patients with myelodysplastic syndrome (MDS) with hypomethylating agents, like decitabine and 5‐azacitidine, has produced favorable results. In this study, the authors update their experience with decitabine in patients with MDS and analyze the cytogenetic response patterns and prognostic factors associated with decitabine therapy.

METHODS.

One hundred fifteen patients with higher risk MDS who received treatment with decitabine were reviewed. Patients received decitabine 100 mg/m2per course every 4 weeks in 3 different schedules: 1) 20 mg/m2intravenously daily × 5, 2) 20 mg/m2subcutaneously daily × 5, and 3) 10 mg/m2intravenously daily × 10. Decitabine was given for a median of ≥7 courses (range, 1–23 courses).

RESULTS.

Overall, 80 patients (70%) achieved a response according to the modified International Working Group criteria (IWG): complete response (CR), 40 patients (35%); partial response, 2 patients (2%); bone marrow CR with or without other hematologic improvements (HI), 26 patients (23%); and other HI, 12 patients (10%). Cytopenias were improved in 50% of patients. The median remission duration was 20 months, and the median survival was 22 months. Mortality was 3% at 6 weeks and 7% at 3 months. In a multivariate analysis, poor prognostic factors for achieving IWG CR were MDS (vs chronic myelomonocytic leukemia), longer duration of MDS, and prior MDS therapy. For survival, independent adverse prognostic factors were chromosome 5 and/or 7 abnormalities, older age, and prior MDS therapy (excluding growth factors).

CONCLUSIONS.

The longer term experience with decitabine in MDS was favorable. Pretreatment prognostic factors may predict the outcome of patients who receive decitabine therapy for MDS. Cancer 2007. © 2006 American Cancer Society.
Clear cell sarcoma of tendons and aponeuroses
Authors: Kawai Akira , Hosono Ako , Nakayama Robert , Matsumine Akihiko , Matsumoto Seiichi , Ueda Takafumi , Tsuchiya Hiroyuki , Beppu Yasuo , Morioka Hideo , Yabe Hiroo ,   for the Japanese Musculoskeletal Oncology Group
Published: November 2006

BACKGROUND.

Clear cell sarcoma (CCS) of tendons and aponeuroses (malignant melanoma of soft parts) is a rare melanocytic soft tissue sarcoma. The objective of this study was to determine the clinical features, prognostic factors, and optimal treatment policy for patients with this rare disease.

METHODS.

Seventy‐five consecutive patients with histologically confirmed CCS who received treatment between 1980 and 2004 were analyzed retrospectively.

RESULTS.

There were 41 men and 34 women, and the median age was 36 years. Sixty‐five tumors were located in the extremities, and 10 tumors were located in the trunk. The median tumor size was 4 cm. Seventy‐one patients underwent surgical excision, and 56 patients received chemotherapy. Sixteen patients developed local recurrences, and 52 patients developed metastasis. The overall patient survival rates was 47% at 5 years and 36% at 10 years. Univariate analysis showed that sex (P= .018), tumor size (P= .001), tumor depth (P= .002), TNM classification (P= .001), and surgical margin (P= .042) were significant prognostic factors. Among the 52 patients who presented with localized disease, sex (P= .023), tumor size (P= .002), tumor depth (P= .011), TNM classification (P= .004), and chemotherapy (P= .032) were identified as significant prognostic factors. Multivariate analysis showed that tumor size remained an independent prognostic factor in both groups.

CONCLUSIONS.

The current results supported the contention that early diagnosis and initial wide excision are essential for a favorable outcome of CCS. The role of chemotherapy for CCS should be investigated further. Cancer 2007. © 2006 American Cancer Society.
Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia
Authors: Rubnitz Jeffrey E. , Razzouk Bassem I. , Lensing Shelly , Pounds Stanley , Pui Ching‐Hon , Ribeiro Raul C.
Published: November 2006

BACKGROUND.

Outcome after recurrence of childhood acute myeloid leukemia (AML) is poor. We performed this study to identify prognostic factors for recurrence and for survival after recurrence of AML.

METHODS.

The clinical characteristics, biological features, treatment modalities, and outcomes of children with de novo AML who were enrolled on 3 consecutive clinical protocols from 1987 to 2002 at St. Jude Children's Research Hospital were studied. Regression modeling was used to identify prognostic factors for recurrence and for survival after recurrence.

RESULTS.

The outcome after recurrence was poor, with a 5‐year survival estimate of only 23.3% ± 5.7%. Multivariable analysis indicated that male sex (P= .005), autologous stem cell transplant before recurrence (P= .097), each additional month from diagnosis to recurrence (P= .041), and stem cell transplant after recurrence (P< .001) were associated with a better survival after recurrence, whereas M5 or M7 morphology (P= .001) were significantly predictive of a lower survival estimate after recurrence.

CONCLUSIONS.

Survival after recurrence was poor in children with AML. Novel therapies are urgently needed to prevent or to treat recurring AML. Cancer 2007. © 2006 American Cancer Society.
Granulocyte– and monocyte–platelet adhesion index in coronary and peripheral blood after extracorporeal circulation and reperfusion
Authors: Sbrana Silverio , Buffa Manuela , Bevilacqua Stefano , Spiller Dario , Parri Maria Serena , Gianetti Jacopo , De Filippis Rossella , Clerico Aldo
Published: November 2006

Background:

Neutrophil‐granulocyte and mononuclear‐cell functional changes occur during cardiopulmonary bypass and cardiovascular surgery. In particular, leukocyte–platelet interaction, leading to generation of heterotypic coaggregates, represents an amplification mechanism of the local inflammatory response and tissue damage.

Methods:

Samples of 20 patients were drawn from venous coronary sinus before cardioplegic arrest and immediately after reperfusion, as well as from peripheral blood at 5 and 24 h postoperatively. The granulocyte and monocyte surface expression of CD162, CD15s, CD18, and CD11b were quantified by flow cytometry at the different times. Parallel variations of circulating leukocyte–platelet conjugates (percentages) and a derived (cell number‐normalized) leukocyte–platelet adhesion index were measured using a combination of antibodies against CD45, CD14, and CD41a. The evaluation of platelet functional state was carried out using antibodies against CD62P (P‐selectin) and PAC‐1.

Results:

Monocyte and granulocyte cell number increased markedly in coronary blood at reperfusion and in peripheral blood postoperatively when compared with measurements done before cardioplegia. A very different course characterized the changes of the leukocyte–platelet adhesion index with respect to the variations of circulating leukocyte–platelet coaggregates (percentages). Leukocyte molecules expression showed no significant variations for CD15s on both the leukocyte subsets, while a significant up‐modulation for CD162 was observed on monocytes at 24 h after extracorporeal circulation (P = 0.0002), and for CD11b on granulocytes at 5 h postoperatively (P = 0.033). A loss of CD162 expression was observed in coronary blood at reperfusion (P = 0.0038) on granulocytes, associated to a down‐modulation of CD18 (P = 0.0033) and CD11b (P = 0.0184) in peripheral blood at 24 h postoperatively. No significant up‐regulation of platelet activatory molecules expression was found at coronary reperfusion, as well as postoperatively in the peripheral blood, when compared with the before‐cardioplegia derived data.

Conclusions:

The over time variations of a normalized leukocyte–platelet adhesion index seem to reflect the cumulative leukocyte–platelet functional interaction more accurately than the parallel measurements of cellular conjugates. The absence of platelet activation suggests that the leukocyte membrane modifications play a main role in controlling the formation and stability of heterotypic leukocyte–platelet coaggregates after cardiac surgery with extracorporeal circulation. © 2006 International Society for Analytical Cytology
Reduced endothelin converting enzyme‐1 and endothelin‐3 mRNA in the developing bowel of male mice may increase expressivity and penetrance of Hirschsprung disease–like distal intestinal aganglionosis
Authors: Vohra Bhupinder P.S. , Planer William , Armon Jennifer , Fu Ming , Jain Sanjay , Heuckeroth Robert O.
Published: November 2006

Hirschsprung disease (distal intestinal aganglionosis, HSCR) is a multigenic disorder with incomplete penetrance, variable expressivity, and a strong male gender bias. Recent studies demonstrated that these genetic patterns arise because gene interactions determine whether enteric nervous system (ENS) precursors successfully proliferate and migrate into the distal bowel. We now demonstrate that male gender bias in the extent of distal intestinal aganglionosis occurs in mice with Ret dominant‐negative mutations (RetDN) that mimic human HSCR. We hypothesized that male gender bias could result from reduced expression of a gene already known to be essential for ENS development. Using quantitative real‐time polymerase chain reaction (PCR) we demonstrated reduced levels of endothelin converting enzyme‐1 and endothelin‐3 mRNA in the male mouse bowel at the time that ENS precursors migrate into the colon. Other HSCR‐associated genes are expressed at comparable levels in male and female mice. Testosterone and Mullerian inhibiting substance had no deleterious effect on ENS precursor development, but adding EDN3 peptide to E11.5 male RetDN heterozygous mouse gut explants in organ culture significantly increased the rate of ENS precursor migration through the bowel. Developmental Dynamics 236:106–117, 2007. © 2006 Wiley‐Liss, Inc.
A Ligand‐Driven Geometry Switch in Octahedral and Trigonal‐Bipyramidal Iron Complexes Containing (H)PNO and PNN Ligands
Authors: Pelagatti Paolo , Bacchi Alessia , Balordi Marcella , Caneschi Andrea , Giannetto Marco , Pelizzi Corrado , Gonsalvi Luca , Peruzzini Maurizio , Ugozzoli Franco
Published: November 2006

Complexation reactions of FeII and FeIII salts with the tridentate ligands 2‐(diphenylphosphanyl)benzaldehyde benzoylhydrazone [(H)PNO] and N‐[2‐(diphenylphosphanyl)benzylidene]‐2‐(2‐pyridyl)ethanamine (PNN) was carried out. For (H)PNO, reaction of a stoichiometric amount of anhydrous FeCl2 in the presence of a primary alcohol such as MeOH, EtOH or nBuOH gave the mixed‐valence FeII/FeIII paramagnetic complex [Fe{κ3‐(H)PNO}2]Cl[FeCl4], whereas the reaction between FeCl2 and a twofold excess of (H)PNO in the presence of AgOTf (OTf = triflate, OSO2CF3) led to the isolation of the bis‐chelate paramagnetic ferrous complex [Fe{κ3‐(H)PNO}2][OTf]2. A diamagnetic bis‐chelate ferrous complex [Fe{κ3‐(PNO)2}] was instead obtained from the reaction of FeCl2 with a twofold excess of (H)PNO in the presence of NaOMe. In the case of the PNN ligand, the 1:1 reaction with FeCl2 gave the neutral paramagnetic trigonal‐bipyramidal complex [Fe(κ3‐PNN)Cl2]. The X‐ray structures of [Fe{κ3‐(H)PNO}2]Cl[FeCl4], [Fe2{κ3‐(H)PNO}2Cl6] and [Fe(κ3‐PNN)Cl2] are reported, together with CV and magnetic susceptibility measurements and an ab initio study aimed at rationalizing the different stoichiometries and structures observed with the two tridentate ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Tuning the Properties of Neutral Tetraazamacrocyclic Complexes of Copper(II) and Nickel(II) for Use as Host–Guest Compounds with Bismacrocyclic Transition Metal Cations
Authors: Rybka Anita , Koliński Ryszard , Kowalski Jarosław , Szmigielski Rafał , Domagała Sławomir , Woźniak Krzysztof , Więckowska Agnieszka , Bilewicz Renata , Korybut‐Daszkiewicz Bohdan
Published: November 2006

The synthesis and structural properties of tetraazamacrocyclic ligands and their neutral and protonated 14‐, 15‐ and 16‐membered complexes of CuII and NiII are described. Molecules of the free 14‐membered ligands have a nonplanar, step‐like structure of the central molecular fragments. Conformational changes are introduced upon protonation, with the protons pointing above and below the macrocycle plane. This prevents the formation of intramolecular N–H···N hydrogen bonds. On insertion of the transition metal ions a planar structure of the macrocycle is obtained, which has consequences for the electrochemical behaviour of the complexes. The deviations from planarity increase with increasing macrocycle size. As a consequence the donor properties are weaker, the redox potential is shifted towards more positive values and the contribution of chemical reactions can be observed. The formation of host–guest complexes between the strongest metal‐containing donors and transition‐metal‐containing bismacrocyclic acceptors of suitable size is proved in solution and the gas phase by voltammetric and ESI MS methods. The transition metal building blocks described in this contribution can be applied in the synthesis of new redox‐active rotaxane and catenane systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis, Structures, and Electronic Spectroscopy of Luminescent Acetylene‐ and (Buta‐1,3‐diyne)platinum Complexes
Authors: Zhang Ke , Hu Jian , Chan Kwok Chu , Wong Kwok Yin , Yip John H. K.
Published: November 2006

The electronic absorption and emission spectroscopy of a series of diphenylaceylene‐ and (buta‐1,3‐diyne)‐Pt0 complexes (L)Pt[(1,2‐η2)‐R–(C≡C)n–R] and [(dppp)Pt]2[μ‐(1,2‐η2):(3,4‐η2)‐R–(C≡C)2–R] {R = Ph or CH3, L = dppp or(PPh3)2, n = 1 or 2} was investigated. The structures of(dppp)Pt[(1,2‐η2)‐Ph–C≡C–Ph], (dppp)Pt[(1,2‐η2)‐PhC4Ph] and [(dppp)Pt]2[μ‐(1,2‐η2):(3,4‐η2)‐Ph–(C≡C)2–Ph] were characterized by X‐ray diffraction. The complexes all display intense absorptions that were attributed to Pt→P(dπ*) and Pt→acetylene(πx*) transitions. Except for the CH3C4CH3 complexes, the complexes all exhibit two emissions at 380–550 nm and 500–800 nm. The higher energy emission could arise from the 3[P(dπ*)→Pt] transition, and the lower energy emission, which has a longer lifetime than the higher energy one, was attributed to the 3[acetylene(πx*)→Pt] transition. The energy of the MLCT absorption and emission was affected by the electronic properties of the acetylenes and the ancillary phosphanes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Regioselective Hydration and Deprotection of Chiral, Dissymmetric Iminodinitriles in the Scope of an Asymmetric Strecker Strategy
Authors: Rossi Jean‐Christophe , Marull Marc , Boiteau Laurent , Taillades Jacques
Published: November 2006

The controlled, selective decomposition of dissymmetric iminodinitriles (DIDN) of formula RCH(CN)–NH–C(CN)R′R″ (considered as N‐protected alpha‐aminonitriles), is a critical issue for an original asymmetric Strecker strategy previously outlined by us for the enantioselective synthesis of amino acids. This strategy, derived from Harada's work, involves a double sequence of (i) stereoselective Strecker condensation of a chiral ketone R′R″CO with NH3 and HCN, followed by (ii) stereoselective Strecker condensation with an aldehyde RCHO and HCN, then (iii) regioselective retro‐Strecker decomposition of the DIDN intermediate to release the target alpha‐aminonitrile. In addition to the use of quite simple, cheap cyclic ketones (e.g. carvone derivatives) as chiral auxiliaries, another great advantage of this strategy is that step (iii) enables the recovery of the chiral ketone and hence its reuse. While our previous investigations on step (iii) under various conditions, either preceded or followed by the hydration of the secondary nitrile group RH(CN)‐ into an amide, had shown insufficient selectivity, we succeeded in the regioselective hydration of the secondary nitrile of DIDN without significant racemisation, by using a large excess of hydrogen peroxide in methanolic/aqueous ammonia (pH 12.5) at low temperature. The resulting imino nitrile/amide compound was then classically decomposed in acidic medium through a retro‐Strecker reaction, affording the chiral alpha‐amino amide. Alternately, the regioselective retro‐Strecker decomposition of the tertiary moiety of the DIDN was achieved by reaction with silver cation in aqueous nitric acid, also without significant racemisation, thus establishing an original, enantioselective synthesis of alpha‐aminonitriles. In both reactions, the chiral ketonic auxiliary resulting from DIDN decomposition was recovered in good yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
In the Search of Glycogen Phosphorylase Inhibitors: Synthesis of C‐D‐Glycopyranosylbenzo(hydro)quinones – Inhibition of and Binding to Glycogen Phosphorylase in the Crystal
Authors: He Li , Zhi Zhang Yun , Tanoh Marcelle , Chen Guo‐Rong , Praly Jean‐Pierre , Chrysina Evangelia D. , Tiraidis Costas , Kosmopoulou Magda , Leonidas Demetres D. , Oikonomakos Nikos G.
Published: November 2006

Penta‐O‐acetyl‐β‐D‐glycopyranoses and 1,4‐dimethoxybenzene led selectively by electrophilic substitution to C‐β‐D‐glycopyranosyl‐1,4‐dimethoxybenzenes which were converted by simple and efficient reactions (oxidation, reduction and deacetylation) to the corresponding C‐glycosylhydro‐ and C‐glycosylbenzoquinones, with either an acetylated or deprotected sugar moiety. C‐β‐D‐Glucosylbenzoquinone 19 and C‐β‐D‐Glucosylhydroquinone 23 were found to be competitive inhibitors of rabbit muscle glycogen phosphorylase b (GPb), with respect to the substrate α‐D‐glucose‐1‐phosphate, with Ki values of 1.3 and 0.9 mM, respectively, whereas C‐β‐D‐glucosylhydroquinone 17 was not effective up to a concentration of 8 mM. In order to elucidate the structural basis of inhibition, we determined the crystal structures of 19 and 23 in complex with GPb at a 2.03–2.05 Å resolution. The complex structures reveal that the inhibitors can be accommodated at the catalytic site at approximately the same position as α‐D‐glucose and stabilise the transition state conformation of the 280s loop by making several favourable contacts to Asp283 and Asn284 of this loop. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Solid‐Phase Synthesis of Acid‐Sensitive N‐(2‐Aminoethyl)glycine‐PNA Oligomers by the Fmoc/Bhoc Strategy
Authors: Stafforst Thorsten , Diederichsen Ulf
Published: November 2006

In the context of investigation of nucleic acid‐mediated excess electron transfer, a bis‐functionalized (2‐aminoethyl)glycine‐PNA modified with a flavin and an oxetane moiety was synthesized. The solid‐phase synthesis of the required PNA oligomer was especially intriguing because of the high acid sensitivity of the oxetane moiety, so the Fmoc/Bhoc strategy was adapted to the mild cleavage conditions of the Sieberamide resin. Along with smooth oligomerization conditions, the syntheses of oxetane‐ and flavin‐functionalized Fmoc‐protected (2‐aminoethyl)glycine building blocks are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Carbon dioxide capture by indirect thermal swing adsorption using 13X zeolite
Authors: Mérel J. , Clausse M. , Meunier F.
Published: November 2006

The aim of this article is to investigate the performances of an indirect temperature swing adsorption process for CO2 removal from nitrogen using 13X zeolite. Breakthrough experiment, with a 10% CO2–N2 mixture, were performed showing that thanks to the cooling, the adsorbent capacity is preserved and close to that of an isothermal adsorption. For the desorption step, CO2 at a concentration of nearly 100% is recovered thanks to the indirect heating and the non‐use of purge gas. During the cycle experiments, we obtained 7.9 MJ/kg for the specific heat consumption. This value is slightly higher than amine absorption ones, which is the reference process for CO2 capture. However, it has to be taken into account that there is a good potential of energy saving because our process configuration (adsorbent choice, number of beds, step duration, etc.) has not been optimized yet. Moreover, in scaled‐up process, the heat losses are of less importance, which will decrease the specific heat consumption. This is confirmed by a first estimation, which gives a value of 5.9 MJ/kg. © 2006 American Institute of Chemical Engineers Environ Prog, 25: 327–333, 2006
Ceramic Supported Capillary Pd Membranes for Hydrogen Separation: Potential and Present Limitations
Authors: Gepert V. , Kilgus M. , Schiestel T. , Brunner H. , Eigenberger G. , Merten C.
Published: November 2006

Composite ceramic capillaries coated with thin palladium membranes are developed for the production of CO‐free hydrogen for PEM fuel cells, via alcohol steam reforming. The composite membranes are tested for pure H2 and N2, as well as for synthetic reformate gas. The aim is to develop a heat‐integrated compact membrane reformer for decentralized hydrogen production. In this context, a deep knowledge of the performance, behavior, and necessary treatment of the composite palladium membranes plays a decisive role in process design. The current contribution focuses on the main hurdles met while attempting to exploit the potential of ceramic supported capillary palladium membranes.
PLP overexpression perturbs myelin protein composition and myelination in a mouse model of Pelizaeus‐Merzbacher disease
Authors: Karim Saadia A. , Barrie Jennifer A. , McCulloch Mailis C. , Montague Paul , Edgar Julia M. , Kirkham Douglas , Anderson Thomas J. , Nave Klaus A. , Griffiths Ian R. , Mclaughlin Mark
Published: November 2006

Duplication of PLP1, an X‐linked gene encoding the major myelin membrane protein of the human CNS, is the most frequent cause of Pelizaeus‐Merzbacher disease (PMD). Transgenic mice with extra copies of the wild type Plp1 gene, a valid model of PMD, also develop a dysmyelinating phenotype dependant on gene dosage. In this study we have examined the effect of increasing Plp1 gene dosage on levels of PLP/DM20 and on other representative myelin proteins. In cultured oligodendrocytes and early myelinating oligodendrocytes in vivo, increased gene dosage leads to elevated levels of PLP/DM20 in the cell body. During myelination, small increases in Plp1 gene dosage (mice hemizygous for the transgene) elevate the level of PLP/DM20 in oligodendrocyte soma but cause only minimal and transient effects on the protein composition and structure of myelin suggesting that cells can regulate the incorporation of proteins into myelin. However, larger increases in dosage (mice homozygous for the transgene) are not well tolerated, leading to hypomyelination and alteration in the cellular distribution of PLP/DM20. A disproportionate amount of PLP/DM20 is retained in the cell soma, probably in autophagic vacuoles and lysosomes whereas the level in myelin is reduced. Increased Plp1 gene dosage affects other myelin proteins, particularly MBP, which is transitorily reduced in hemizygous mice but consistently and markedly lower in homozygotes in both myelin and naïve or early myelinating oligodendrocytes. Whether the reduced MBP is implicated in the pathogenesis of dysmyelination is yet to be established. © 2006 Wiley‐Liss, Inc.
Abnormal activation of the social brain during face perception in autism
Authors: Hadjikhani Nouchine , Joseph Robert M. , Snyder Josh , Tager‐Flusberg Helen
Published: November 2006

ASD involves a fundamental impairment in processing social‐communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face‐processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity‐processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face‐related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face‐processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face‐processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face‐processing disturbances in ASD. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
A glimpse into your vision
Authors: Gonzalez Andino Sara L. , Grave de Peralta Rolando , Khateb Asaid , Pegna Alan J. , Thut Gregor , Landis Theodor
Published: November 2006

Invasive recordings of local field potentials (LFPs) have been used to “read the mind” of monkeys in real time. Here we investigated whether noninvasive field potentials estimated from the scalp‐recorded electroencephalogram (EEG) using the ELECTRA source localization algorithm could provide real‐time decoding of mental states in healthy humans. By means of pattern recognition techniques on 500‐ms EEG epochs, we were able to discriminate accurately from single trials which of four categories of visual stimuli the subjects were viewing. Our results show that it is possible to reproduce the decoding accuracy previously obtained in animals with invasive recordings. A comparison between the decoding results and the subjects' behavioral performance indicates that oscillatory activity (OA), elicited in specific brain regions) codes better for the visual stimulus category presented than the subjects' actual response, i.e., is insensitive to voluntary or involuntary errors. The identification of brain regions participating in the decoding process allowed us to construct 3D‐functional images of the task‐related OA. These images revealed the activation of brain regions known for their involvement in the processing of this type of visual stimuli. Electrical neuroimaging therefore appears to have the potential to establish what the brain is processing while the stimuli are being seen or categorized, i.e., concurrently with sensory‐perceptual processes. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of PCA and ICA of simulated ERPs: Promax vs. infomax rotations
Authors: Dien Joseph , Khoe Wayne , Mangun George R.
Published: November 2006

Independent components analysis (ICA) and principal components analysis (PCA) are methods used to analyze event‐related potential (ERP) and functional imaging (fMRI) data. In the present study, ICA and PCA were directly compared by applying them to simulated ERP datasets. Specifically, PCA was used to generate a subspace of the dataset followed by the application of PCA Promax or ICA Infomax rotations. The simulated datasets were composed of real background EEG activity plus two ERP simulated components. The results suggest that Promax is most effective for temporal analysis, whereas Infomax is most effective for spatial analysis. Failed analyses were examined and used to devise potential diagnostic strategies for both rotations. Finally, the results also showed that decomposition of subject averages yield better results than of grand averages across subjects. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Interparticipant correlations: A model free FMRI analysis technique
Authors: Hejnar Martin P. , Kiehl Kent A. , Calhoun Vince D.
Published: November 2006

FMRI analysis techniques can be broadly divided into model based and data driven techniques. The most widely used approach assumes an explicit temporal hemodynamic model based upon the experimental paradigm. Such an approach has proven very useful and powerful even though it is limited by the accuracy of the prespecified model. An alternative approach is to use data driven techniques like independent component analysis or fuzzy cluster analysis. These approaches have proven useful for exploratory analysis in a multivariate sense; however, they can present additional difficulties in the interpretation of the results. An alternative to these approaches is to take advantage of similarities in the patterns of the hemodynamics between participants [i.e., interparticipant correlation (IPC)]. This FMRI analysis technique enjoys the parsimony of the general linear model (GLM) but does not assume a specific FMRI time course. The technique consists of calculating voxel‐wise correlations between participants resulting in IPC maps, which indicate the activated regions the participants have in common. We applied the IPC approach to data collected from healthy controls in an auditory oddball task. As expected, high inter‐participant correlations were detected in auditory cortical regions in the temporal lobes where highest correlations were evident. In addition, areas that appear to be involved in the task were detected using IPC's but not the GLM regression. This technique, designed to have increased sensitivity to inter‐subject correlations that are not necessarily task‐related, may potentially be useful as a compliment to model‐based approaches. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Taxing working memory with syntax: Bihemispheric modulations
Authors: Santi Andrea , Grodzinsky Yosef
Published: November 2006

Motivated by claims that relegate the syntactic functions of Broca's region to working memory (WM) and not to language‐specific mechanisms, we conducted an fMRI and an aphasia study that featured two varieties of intrasentential dependency relations: One was syntactic movement (e.g.,Which boy does the girl think◂examined Steven?), the other was antecedent–reflexive binding (e.g.,Jill thinks the boy examined himself). In both, WM is required to link two nonadjacent positions. Syntactically, they are governed by distinct rule systems. In health, the two dependencies modulated activity in distinct brain regions within the left inferior frontal gyrus and the left middle temporal gyrus. Binding uniquely modulated activation in the right frontal lobe. Receptive abilities in brain damaged patients likewise distinguished among these syntactic types. The results indicate that sentence comprehension is governed by syntactically carved neural chunks and provide hints regarding a language related region in the right hemisphere. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection
Authors: Lagging Martin , Romero Ana I. , Westin Johan , Norkrans Gunnar , Dhillon Amar P. , Pawlotsky Jean-Michel , Zeuzem Stefan , von Wagner Michael , Negro Francesco , Schalm Solko W. , Haagmans Bart L. , Ferrari Carlo , Missale Gabriele , Neumann Avidan U. , Verheij-Hart Elke , Hellstrand Kristoffer
Published: November 2006

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-α-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (

P

< .0001), even in those with body mass index (BMI) ≥ 25 kg/m2 (

P

= .004) and with baseline viral load ≥ 2 million IU/mL (

P

= .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (

P

= .0002), including those having higher BMI (

P

< .05), higher viral load (

P

= .0005), and both higher BMI and viral load (

P

< .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1–infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively.

In conclusion

, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.
STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity
Authors: Jeong Won-Il , Park Ogyi , Radaeva Svetlana , Gao Bin
Published: November 2006

Liver fibrosis, a common scarring response to chronic liver injury, is a precursor to cirrhosis and liver cancer. Here, we identified signal transducer and activator of transcription 1 (STAT1) as an important negative regulator in liver fibrosis. Our findings show that disruption of the STAT1 gene accelerated liver fibrosis and hepatic stellate cell (HSC) proliferation in an

in vivo

model of carbon tetrachloride (CCl4)-induced liver fibrosis.

In vitro

treatment with IFN-γ inhibited proliferation and activation of wild-type HSCs, but not STAT1−/− HSCs. Moreover, compared to wild-type cells, cellular proliferation stimulated by serum or platelet-derived growth factor (PDGF) was enhanced and accelerated in STAT1−/− HSCs, which was partially mediated via elevated PDGF receptor β expression on such cells. Polyinosinic-polycytidylic acid (poly I:C) or IFN-γ treatment inhibited liver fibrosis in wild-type mice but not in STAT1−/− mice. Induction of NK cell killing of activated HSCs by poly I:C was attenuated in STAT1−/− mice compared to wild-type mice, which was likely due to reduced NKG2D and TRAIL expression on STAT1−/− NK cells. Finally, activation of TGF-β/Smad3 signaling pathway was accelerated, whereas induction of Smad7 was diminished in the liver of STAT1−/− mice after CCl4 administration compared to wild-type mice.

In conclusion

, activation of STAT1 attenuates liver fibrosis through inhibition of HSC proliferation, attenuation of TGF-β signaling, and stimulation of NK cell killing of activated HSCs. STAT1 could be a new therapeutic target for treating liver fibrosis.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation
Authors: Prytz Hanne , Keiding Susanne , Björnsson Einar , Broomé Ulrika , Almer Sven , Castedal Maria , Munk Ole Lajord
Published: November 2006

Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC; however, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver.

In conclusion

, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC.
Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice
Authors: Lieu Hanh-Tu , Simon Marie-Thérèse , Nguyen-Khoa Thao , Kebede Messeret , Cortes Alexandre , Tebar Luis , Smith Andrew J. H. , Bayne Rosemary , Hunt Stephen P. , Bréchot Christian , Christa Laurence
Published: November 2006

Reg2/RegIIIβ is the murine homologue of the human secreted HIP/PAP C-type lectin. HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy. To assess the role of Reg2, we used Reg2−/− mice in a model of fulminant hepatitis induced by Fas and in the post-hepatectomy regeneration. Within 4 hours of J0-2 treatment (0.5 μg/g), only 50% of the Reg2−/− mice were alive but with an increased sensitivity to Fas-induced oxidative stress and a decreased level of Bcl-xL. In contrast, HIP/PAP transgenic mice were resistant to Fas, with HIP/PAP serving as a sulfhydryl buffer to slow down decreases in glutathione and Bcl-xL. In Reg2−/− mice, liver regeneration was markedly impaired, with 29% mortality and delay of the S-phase and the activation of ERK1/2 and AKT. Activation of STAT3 began on time at 3 hours but persisted strongly up to 72 hours despite significant accumulation of SOCS3. Thus, Reg2 deficiency induced exaggerated IL-6/STAT-3 activation and mito-inhibition. Because the

Reg2

gene was activated between 6 and 24 hours after hepatectomy in wild-type mice, Reg2 could mediate the TNF-α/IL-6 priming signaling by exerting a negative feed-back on STAT3/IL-6 activation to allow the hepatocytes to progress through the cell cycle.

In conclusion

, Reg2 deficiency enhanced liver sensitivity to Fas-induced oxidative stress and delayed liver regeneration with persistent TNF-α/IL6/STAT3 signaling. In contrast, overexpression of human HIP/PAP promoted liver resistance to Fas and accelerated liver regeneration with early activation/deactivation of STAT3. Reg2/HIP/PAP is therefore a critical mitogenic and antiapoptotic factor for the liver.
Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial
Authors: Everson Gregory T. , Hoefs John C. , Seeff Leonard B. , Bonkovsky Herbert L. , Naishadham Deepa , Shiffman Mitchell L. , Kahn Jeffrey A. , Lok Anna S. F. , Di Bisceglie Adrian M. , Lee William M. , Dienstag Jules L. , Ghany Marc G. , Morishima Chihiro
Published: November 2006

In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon ± RBV and had Ishak fibrosis scores ≥ 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts >125,000/mm3 (n = 559); (B) bridging fibrosis with platelet counts ≤125,000/mm3 (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts >125,000/mm3 (n = 198); and (D) cirrhosis with platelet counts ≤125,000/mm3 (n = 193). SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively (

P

< .0001 for trend). Reduction in SVR as a function of increasingly severe disease was independent of age, percent African American, HCV genotype, HCV level, and type of prior therapy. Dose reduction lowered SVR frequencies, but to a lesser extent than disease severity. By logistic regression, cirrhosis (

P

< .0001) was the major determinant that impaired virologic response, independent of dose reduction or platelet count.

In conclusion

, disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these “difficult-to-cure” patients.
Assessing drainage water reuse options in Bojili Irrigation District, Shandong
Authors: Minhas P. S. , Tyagi N. K. , Gupta S. K. , Dong K. L. , Cai L. G. , Pereira L. S.
Published: November 2006

For assessing the potential and need to reuse surface drainage and groundwater for sustainable crop production in the Shandong province of the Yellow River basin, inventories were made on the quality of alternative sources of irrigation and on the yields achieved by farmers using those waters for irrigation. Drainage and groundwater quality (EC < 2 dS m−1) in most parts of Huimin and Yangxin counties favors their use for irrigation but there can be some limitations in Wudy as the salinity increases towards the sea. Yield–soil salinity functions were developed for both maize and wheat; for the latter, functions depend upon the number of irrigations applied. Simulations using the SWAP model showed that yields of wheat and maize could be sustained with the reuse of drainage water having a salt content up to 4 mg cm−3. There is a clear benefit from using drainage water for the last two wheat irrigations relative to deficit irrigation despite water salinity. Monsoon rainfall should help to maintain a favorable salt balance, thus to avoid salt build‐up along the soil profile. Results indicate that the reuse of drainage waters offers opportunities for improving irrigation water management in wheat for areas facing water shortage. Copyright © 2006 John Wiley & Sons, Ltd.
Effects of chemicals on root intrusion into subsurface drip emitters
Authors: Suarez‐Rey Elisa M. , Choi Christopher Y. , McCloskey William B. , Kopec David M.
Published: November 2006

Root intrusion into emitters poses a threat to the long‐term success of subsurface drip irrigation systems, particularly in fibrous‐rooted crops. Bermudagrass was grown in a greenhouse to examine the effectiveness of chemicals in preventing root intrusion into subsurface drip emitters in two‐year, two‐part experiments. During the first year of study, two acids, sulfuric and phosphoric, and two pre‐emergence herbicides, trifluralin and thiazopyr, were tested on bermudagrass grown in small pots. As an initial step for the emitter clogging experiment, the first‐year experiment focused on the effectiveness of the chemicals in preventing overall root growth in pots saturated with either trifluralin or thiazopyr. Only thiazopyr significantly inhibited root growth, and visual quality of shoot growth in the thiazopyr‐treated pots was lower than the observed quality in the rest of the treatments and in non‐treated bermudagrass. During the second year, nine treatments were prepared based on the first‐year study, and were examined for control of root intrusion into actual subsurface drip emitters. Emitters were completely free of roots with thiazopyr treatment at the highest concentration, and with the trifluralin‐impregnated emitter treatment under water stress. Root and rhizome growth was generally unaffected by treatment. As expected, shoot visual quality was lowest in the thiazopyr treatments. Nevertheless, it met the minimum quality standard. Copyright © 2006 John Wiley & Sons, Ltd.