bluuebunny/crossref_metadata_2025 huggingface dataset:
A Photochemical Activation Scheme of Inert Dinitrogen by Dinuclear RuII and FeII Complexes
Authors: Reiher Markus , Kirchner Barbara , Hutter Jürg , Sellmann Dieter , Hess Bernd Artur
Published: July 2004

A general photochemical activation process of inert dinitrogen coordinated to two metal centers is presented on the basis of high‐level DFT and ab initio calculations. The central feature of this activation process is the occupation of an antibonding π* orbital upon electronic excitation from the singlet ground state S0 to the first excited singlet state S1. Populating the antibonding LUMO weakens the triple bond of dinitrogen. After a vertical excitation, the excited complex may structurally relax in the S1 state and approaches its minimum structure in the S1 state. This excited‐state minimum structure features the dinitrogen bound in a diazenoid form, which exhibits a double bond and two lone pairs localized at the two nitrogen atoms, ready to be protonated. Reduction and de‐excitation then yield the corresponding diazene complex; its generation represents the essential step in a nitrogen fixation and reduction protocol. The consecutive process of excitation, protonation, and reduction may be rearranged in any experimentally appropriate order. The protons needed for the reaction from dinitrogen to diazene can be provided by the ligand sphere of the complexes, which contains sulfur atoms acting as proton acceptors. These protonated thiolate functionalities bring protons close to the dinitrogen moiety. Because protonation does not change the π*‐antibonding character of the LUMO, the universal and well‐directed character of the photochemical activation process makes it possible to protonate the dinitrogen complex before it is irradiated. The π*‐antibonding LUMO plays the central role in the activation process, since the diazenoid structure was obtained by excitation from various occupied orbitals as well as by a direct two‐electron reduction (without photochemical activation) of the complex; that is, the important bending of N2 towards a diazenoid conformation can be achieved by populating the π*‐antibonding LUMO.
Topological Analysis of Electron Densities: Is the Presence of an Atomic Interaction Line in an Equilibrium Geometry a Sufficient Condition for the Existence of a Chemical Bond?
Authors: Haaland Arne , Shorokhov Dimitry J. , Tverdova Natalya V.
Published: July 2004

The structure, energetics, and electron density in the inclusion complex of He in adamantane, C10H16, have been studied by density functional theory calculations at the B3LYP6‐311++G(2p,2d) level. Topological analysis of the electron density shows that the He atom is connected to the four tertiarytC atoms in the cage by atomic interaction lines with (3,−1) critical points. The calculated dissociation energy of the complex He@adamantane(g)=adamantane(g) + He(g) of ΔE=−645 kJ mol−1nevertheless shows that the He–tC interactions areantibonding.
Stereochemical studies of chiral resolving agents, M9PP and H9PP acids
Authors: Ichikawa Akio , Ono Hiroshi , Harada Nobuyuki
Published: July 2004

The stereoselective Grignard reaction of (1R,2S,5R)‐(–)‐2‐isopropyl‐5‐methylcyclohexyl pyruvate (menthyl pyruvate) with 9‐phenanthrylmagnesium bromide yielded diastereomeric hydroxy‐esters, where intramolecular OH…O=C hydrogen bond was observed in IR and 1H NMR spectra. The alkaline hydrolysis of the major product gave (+)‐2‐hydroxy‐2‐(9‐phenanthryl)propionic acid (H9PP acid (3)), whose absolute configuration was assigned as S based on the chemical correlation with (1R,2S,5R)‐2‐isopropyl‐5‐methylcyclohexyl ester of (S)‐2‐methoxy‐2‐(9‐phenanthryl)propionic acid (M9PP acid (2)); the absolute configuration of 2 had been previously established by X‐ray crystallography. The enantioresolution of (±)‐6‐methyl‐5‐hepten‐2‐ol, sulcatol, an insect pheromone, was carried out using (S)‐(+)‐M9PP acid 2. Chirality 16:559–567, 2004. © 2004 Wiley‐Liss, Inc.
Prognostic value of P53, MDM‐2, and MUC‐1 for patients with inflammatory breast carcinoma
Authors: Resetkova Erika , Gonzalez‐Angulo Ana M. , Sneige Nour , Mcdonnell Timothy J. , Buzdar Aman U. , Kau Shu Wan , Yamamura Yuko , Reuben James M. , Hortobagyi Gabriel N. , Cristofanilli Massimo
Published: July 2004

BACKGROUND

Inflammatory breast carcinoma (IBC) is a rare and aggressive malignancy. Therapy for patients with IBC is multidisciplinary, and response to preoperative chemotherapy is considered an important predictor of outcome. Although only a limited number of molecular markers have been investigated in this setting, none has exhibited prognostic value for patients with IBC.

METHODS

Immunohistochemical assays for P53, MDM‐2, and MUC‐1 were performed retrospectively to evaluate potential correlations between these markers and pathologic response, time to progression (TTP), and overall survival (OS) in 19 patients with IBC.

RESULTS

After a median follow‐up period of 46 months, patients with tumors that overexpressed P53 and did not express MUC‐1 had a significantly shorter median TTP and median OS compared with other patients.

CONCLUSIONS

Expression of P53 and MUC‐1 may be predictive of treatment efficacy and outcome for patients with IBC. Furthermore, these two markers may represent novel therapeutic targets in such patients. Cancer 2004. © 2004 American Cancer Society.
Combination chemotherapy (cyclophosphamide, doxorubicin, and vincristine with continuous‐infusion cisplatin and etoposide) and radiotherapy with stem cell support can be beneficial for adolescents and adults with estheisoneuroblastoma
Authors: Mishima Yuko , Nagasaki Eijiro , Terui Yasuhito , Irie Tetsuya , Takahashi Shunji , Ito Yoshinori , Oguchi Masahiko , Kawabata Kazuyoshi , Kamata Shinetsu , Hatake Kiyohiko
Published: July 2004

BACKGROUND

Adolescent‐onset and adult‐onset esthesioneuroblastoma is a rare disease and is considered incurable. In many patients, local resection and radiation are chosen as clinical therapy with or without chemotherapy. It was reported previously that local resection and radiotherapy led to temporary remission and, in many patients, recurrent disease. Although combination with chemotherapy has been regarded as promising, an effective regimen has not been established. In the current study, the authors investigated the effect and tolerability of the combination of chemotherapy, radiotherapy, and peripheral blood stem cell transplantation (PBSCT).

METHODS

The study population included 12 patients with adolescent‐onset and adult‐onset esthesioneuroblastoma classified as Kadish Stage A–D. The patients received two cycles of combination chemotherapy, which consisted of cyclophosphamide, doxorubicin, and vincristine (CAD) with continuous‐infusion cisplatin and etoposide (CVP). This was combined with radiotherapy with or without PBSCT.

RESULTS

Nine of 12 patients (75%) obtained more than a partial response after only 2 cycles of chemotherapy. After radiation with or without PBSCT, six patients obtained a complete remission (CR). The longest survival was > 3 years. All patients who underwent PBSCT obtained a CR. The most severe side effects were loss of sodium and potassium induced by cisplatin‐related renal tubular distress. Those abnormalities were temporary, and all patients recovered.

CONCLUSIONS

The chemotherapy regimen with CADO and CVP does not require continuation for a long time and is very effective and tolerable for patients with adolescent‐onset and adult‐onset esthesioneuroblastoma. The combination with radiotherapy and PBSCT may lead to a CR without facial disfigurement. In this report, the authors discuss the feasibility and efficacy of this multidisciplinary approach. Cancer 2004. © 2004 American Cancer Society.
LAMP‐1 and LAMP‐2, but not LAMP‐3, are reliable markers for activation‐induced secretion of human mast cells
Authors: Grützkau Andreas , Smorodchenko Alina , Lippert Undine , Kirchhof Loreen , Artuc Metin , Henz Beate M.
Published: July 2004

Background

Mast cells are resident tissue cells that induce anaphylactic reactions by rapidly releasing mediators after antigen‐mediated cross‐linking of immunoglobulin E receptors. In the similarly active peripheral blood basophilic leukocyte, lysosome‐associated membrane protein 3 (LAMP‐3; CD63) has been described as an activation marker, but LAMPs have not been investigated in normal tissue mast cells.

Methods

Intra‐ and extracellular expressions of LAMP‐1 (CD107a), LAMP‐2 (CD107b), and LAMP‐3 (CD63) were analysed by flow cytometry, immunocytochemistry, and functional assays in unstimulated and stimulated leukemic human mast cell line 1 (HMC‐1) and skin mast cells.

Results

On flow cytometry, all mast cells expressed LAMP‐3 at their cell membranes, whereas LAMP‐1 and LAMP‐2 were barely detectable (HMC‐1 cells) or expressed at low levels (<10% of skin mast cells). After fixation and permeabilisation, high intracellular levels of all three LAMPs were noted in both cell types. After stimulation, a rapid translocation of intracellular LAMPs to the cell membrane, with an associated release of histamine, leukotriene C4 and prostaglandin D2, was ascertained in skin mast cells only.

Conclusion

These results show that LAMP‐1 and LAMP‐2 are activation markers for normal mast cells. The lack of LAMP translocation after activation of leukemic mast cells may be related to maturation or malignancy‐associated defects of these cells. © 2004 Wiley‐Liss, Inc.
NKT cell ligand α‐galactosylceramide blocks the induction of oral tolerance by triggering dendritic cell maturation
Authors: Chung Yeonseok , Chang Woo‐Sung , Kim Sanghee , Kang Chang‐Yuil
Published: July 2004

NKT cells play contradictory roles in vivo, both regulating autoimmunity and activating immunity to intracellular pathogens and tumors. In this study, we studied the effect of NKT cell activation on the induction of systemic tolerance by oral administration of antigen. Administration of α‐galactosylceramide (αGC) at the time of oral ovalbumin (OVA) feeding completely blocked the OVA‐specific tolerance induced by both high‐ and low‐dose regimens in BALB/c mice. In the mesenteric lymph nodes (MLN) of αGC‐treated mice, the proliferation of OVA‐specific T cells was greater than that seen in the MLN of vehicle‐treated mice in vivo. The administration of αGC triggered the full maturation of mesenteric dendritic cells (DC), which were in turn responsible for the enhanced division of OVA‐specific T cells in vitro. To further determine whether the costimulation provided by DC in αGC‐treated mice was responsible for the reversal of oral tolerance in vivo, mice were given αGC together with anti‐CD80 and anti‐CD86 blocking Ab. OVA‐specific systemic tolerance was restored in mice given the blocking Ab, even when they simultaneously received αGC. Therefore, oral tolerance can be reversed via costimulation by DC that have been triggered to fully mature by the administration of αGC.
Potent T cell response to a class I‐binding 13‐mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length
Authors: Green Kate J. , Miles John J. , Tellam Judy , van Zuylen Wendy J. M. , Connolly Geoff , Burrows Scott R.
Published: July 2004

The BZLF1 antigen of Epstein‐Barr virus includes three overlapping sequences of different lengths that conform to the binding motif of human leukocyte antigen (HLA) B*3501. These 9‐mer (56LPQGQLTAY64), 11‐mer (54EPLPQGQLTAY64), and 13‐mer (52LPEPLPQGQLTAY64) peptides all bound well to B*3501; however, the CTL response in individuals expressing this HLA allele was directed strongly and exclusively towards the 11‐mer peptide. In contrast, EBV‐exposed donors expressing HLA B*3503 showed no significant CTL response to these peptides because the single amino acid difference between B*3501 and B*3503 within the F pocket inhibited HLA binding by these peptides. The extraordinarily long 13‐mer peptide was the target for the CTL response in individuals expressing B*3508, which differs from B*3501 at a single position within the D pocket (B*3501, 156Leucine; B*3508, 156Arginine). This minor difference was shown to enhance binding of the 13‐mer peptide, presumably through a stabilizing interaction between the negatively charged glutamate at position 3 of the peptide and the positively charged arginine at HLA position 156. The 13‐mer epitope defined in this study represents the longest class I‐binding viral epitope identified to date as a minimal determinant. Furthermore, the potency of the response indicates that peptides of this length do not present a major structural barrier to CTL recognition.
New N,N‐Diisopropylcarbamato Complexes of Ruthenium(II) as Catalytic Precursors for Olefin Hydrogenation
Authors: Belli Dell'Amico Daniela , Calderazzo Fausto , Englert Ulli , Labella Luca , Marchetti Fabio , Specos Monica
Published: July 2004

During the synthesis of [Ru(O2CNiPr2)2(PPh3)2] (1), the [RuCl2(PPh3)3]/NHiPr2/CO2 system produces the intermediates [NH2iPr2][Ru2Cl2(μ‐Cl)3(PPh3)4] (2) and [RuCl(O2CNiPr2)(PPh3)3] (3) which have been isolated and fully characterised. Compound 2 contains the dinuclear anionic triply chloride‐bridged ruthenium(II) species. Compound 3 is mononuclear, the octahedral ruthenium centre being coordinated to the bidentate carbamato ligand. The reactions of compounds 1 and 3 with dihydrogen have been studied at room temperature and atmospheric pressure with respect to their catalytic hydrogenation of 1‐octene. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Hydrothermal Synthesis, Structure and Magnetic Properties of a One‐Dimensional Iron Arsenate, 1∞[NH3(CH2)2NH(CH2)2NH3][Fe2F4(HAsO4)2]
Authors: Chakrabarti Sandip , Pati Swapan K. , Green Mark A. , Natarajan Srinivasan
Published: July 2004

A novel one‐dimensional iron arsenate, 1∞[NH3(CH2)2NH(CH2)2NH3][Fe2F4(HAsO4)2], built up exclusively from SBU‐4 units (two octahedral units sharing an edge and connected through two tetrahedra) with Fe3+ ions in the high‐spin state has been synthesized by hydrothermal methods. Structure elucidation reveals that the compound is a two‐leg ladder with very weak antiferromagnetic exchanges along the chains. The magnetic susceptibility data show activated behaviour at T = 14 K, suggesting a finite spin gap between the nonmagnetic ground state and the excited triplet state. We have estimated the exchange parameters theoretically based on the S = 5/2 Majumdar−Ghosh model with frustrations and dimerisations. Although the magnetic gap is quite small, this is the first example, to the best of our knowledge, where the rungs with two S = 5/2 spins form strong singlet dimers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Discrete Dinuclear Complexes and Two‐Dimensional Architectures from Bridging Polynitrile and Bipyrimidine (bpym) Ligands: Syntheses, Structures and Magnetic Properties of [M2(bpym)(dcne)4(H2O)2] (M = MnII, CoII) and [M2(bpym)(dcne)4(H2O)4]·2H2O (M = FeII, CuII) (dcne− = [(CN)2CC(O)OEt)]−)
Authors: Thétiot Franck , Triki Smail , Sala Pala Jean , Galán‐Mascarós José‐Ramón , Martínez‐Agudo José M. , Dunbar Kim R.
Published: July 2004

One‐pot reactions in aqueous solutions of the polynitrile anion dcne− {2,2‐dicyano‐1‐ethoxyethenolate = [(CN)2CC(O)OEt)]−] with the MII ions (M = Mn, Fe, Co, Cu) in the presence of bpym (2,2′‐bipyrimidine) afford the first mixed dcne/bpym compounds [M2(bpym)(dcne)4(H2O)2] (1: M = Mn; 2: M = Co) and [M2(bpym)(dcne)4(H2O)4]·2H2O (3: M = Fe; 4: M = Cu). The new compounds have been characterized by IR spectroscopy and X‐ray crystallography. Compounds 1 and 2 are isostructural, with each metal ion being located in an MN5O pseudo‐octahedral environment with three N atoms coming from three dcne− ligands, two nitrogen atoms from bpym and one oxygen atom from a water molecule. The extended structures of 1 and 2 are best described as dcne‐bridged zigzag chains of MII ions running along the [100] direction; connections of these chains in the [010] direction, by the bis(chelating) bpym ligand, afford 2D structures. Compounds 3 and 4 are isostructural, and consist of discrete dinuclear units involving MN4O2 octahedrally coordinated MII ions bridged by bis(bidentate) 2,2′‐bipyrimidine and terminal dcne ligands. Magnetic measurements for the 2D compounds 1 and 2 exhibit maxima in the χm vs. T plots (at about 4.5 K for 1 and about 20 K for 2) which are characteristic of weak antiferromagnetic exchange interactions between the high‐spin metal centres. While the dinuclear iron complex 3 presents a similar behaviour (maximum in χm vs. T plot at 12 K), the antiferromagnetic exchange interactions are stronger in the copper complex 4. Fits of magnetic data for compounds 1, 3 and 4 with appropriate models led to J values of −0.6, −1.5 and −99.0 cm−1 respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Stabilization of a Copper(II) Complex by Hydrogen Bonds between the Axial Tetrafluoroborate Anion and the Ammonium Group from the Coordinated Cationic Ligand Bis(imidazol‐2‐yl)methyl(isopropyl)ammonium
Authors: Song Yufei , Massera Chiara , Gamez Patrick , Manotti Lanfredi Anna Maria , Reedijk Jan
Published: July 2004

A new mononuclear copper complex [Cu(HIm‐iPr)2(BF4)2](BF4)2·2CH3OH {where Im‐iPr is [bis(imidazol‐2‐yl)methyl](isopropyl)amine} has been obtained by diethyl ether diffusion into a methanol solution of Im‐iPr and Cu(BF4)2. The complex has been characterized by X‐ray analysis, UV/Vis, IR and EPR spectroscopy. Its crystal structure is built up by centrosymmetric [Cu(HIm‐iPr)2(BF4)2]2+ complex cations, BF4− counterions and methanol lattice molecules. In the cation, the Cu atom exhibits a distorted octahedral CuN4F2 chromophore coordinated by two axial BF4− ions and by four equatorial imidazole nitrogen atoms from two cationic HIm‐iPr ligands. The complex is stabilized by two intramolecular pseudo‐chelate hydrogen bonds between the axial BF4− ions and the ammonium nitrogen atoms of the HIm‐iPr ligand [N5···F8 = 2.761(5) Å]. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Microwave‐Assisted Generation of Lanthanide(II) Halides in THF and Simple Quantitative Determination
Authors: Dahlén Anders , Hilmersson Göran
Published: July 2004

Lanthanide(II) reagents (SmI2, SmBr2, YbI2, EuI2) have been prepared rapidly in high yields using microwave‐assisted heating. Samarium diiodide is obtained as a saturated solution in THF (0.13M) within 5 min and ytterbium diiodide (0.065M) after 45 min. A simple method for quantitative determination of LnX2in THF is also described by utilizing the instantaneous reaction with ketones in the presence of an amine and water. This method establishes the concentration of the active single‐electron‐donor species, i.e. Ln2+. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Novel Phosphovanadate Layered Structure Assembled from a Tetrametallic Cubane‐Like VV Cluster (Eur. J. Inorg. Chem. 15/2004)
Authors: Shi Fa‐Nian , Paz Filipe A. Almeida , Rocha João , Klinowski Jacek , Trindade Tito
Published: July 2004

The cover picture shows a view in perspective of a novel phosphovanadate layered structure intercalated by 4,4′‐bipyridinium cations which act as hydrogen‐bonded pillars between adjacent layers. These inorganic layers are constructed by an unprecendented secondary tetrametallic VV building unit exhibiting a distorted cubane‐type structural motif. Details are discussed in the article by J. Rocha et al. on p. 3031 ff.
Signiﬁcance of changed climatic factors on essential oil composition of Echinacea purpurea under subtropical conditions
Authors: Thappa R. K. , Bakshi S. K. , Dhar P. L. , Agarwal S. G. , Kitchlu S. , Kaul M. K. , Suri K. A.
Published: July 2004

Variation pattern in the composition of essential oil, hydrodistilled from the over‐matured ﬂower heads of Echinacea purpurea (L.) Moench under subtropical climate was characterized by GC–MS and GC analysis. The plants ﬂower from June till December and climatic factors such as temperature and humidity were found to affect both the content and the composition of the essential oil. Copyright © 2004 John Wiley & Sons, Ltd.
Essential oil composition of Satureja spicigera (C. Koch) Boiss. from Iran
Authors: Seﬁdkon F. , Jamzad Z.
Published: July 2004

Hydro‐distilled volatile oil from the aerial parts of Satureja spicigera (C. Koch) Boiss. was obtained at yield of 3.82% w/w based on dry weight. The oil was analyzed by a combination of GC and GC/MS. Forty‐eight components were identiﬁed that approximately constitute 96% of the oil. The main constituents of the essential oil were thymol (35.1%), p‐cymene (22.1%), γ‐terpinene (13.7%) and carvacrol (4.0%). Copyright © 2004 John Wiley & Sons, Ltd.
The essential oil of Tagetes erecta L. occurring in Iran
Authors: Seﬁdkon F. , Salehyar S. , Mirza M. , Dabiri M.
Published: July 2004

Hydro‐distilled volatile oils from the leaves and stems and the ﬂowers of Tagetes erecta L. were analyzed by a combination of GC and GC/MS. Thirty‐three components in leaf and stem oil and 34 components in ﬂower oil were identiﬁed. The main characterized constituents were β‐caryophyllene (8.5 and 35.2%), terpinolene (18.4 and 6.3%), (E)‐ocimenone (12.6 and 9.8%), (Z)‐β‐ocimene (10.4 and 13.7%), piperitenone (10.4 and 2.6%), (Z)‐ocimenone (5.5 and 7.7%) and limonene (6.2 and 2.5%) in leaf and stem and ﬂower oils respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Ein Protein erscheint in einem neuen Licht
Authors: Herzog Volker , Kirfel Gregor , Schmitz Anton , Tikkanen Ritva
Published: July 2004

Für die Alzheimersche Krankheit könnte auch das Protein sAPP mitverantwortlich sein. Welche Aufgaben dieses Protein im menschlichen Organismus übernimmt, ist deshalb nicht nur für den Grundlagenforscher aufschlussreich
Das System Erde
Authors: Dürr Sören
Published: July 2004

Junge Nachwuchswissenschaftler tagten gemeinsam mit amerikanischen Kollegen in Washington
Der Computer und die Operation Schädeldecke
Authors: Eufinger Harald , Weihe Stephan , Wehmöller Michael
Published: July 2004

Um Lücken in der Schädeldecke zu schließen, werden Titanimplantate passgenau eingesetzt. Dabei können computergestützte Verfahren und Roboter helfen, die in enger Kooperation zwischen Medizinern und Ingenieuren entwickelt werden
Von Schlickwatt, Mischwatt und Sandwatt
Authors: Rullkötter Jürgen
Published: July 2004

Ausgedehnte Wattflächen sind das Ergebnis der Gezeiten in verschiedenen Klimazonen der Erde. Am Beispiel der südlichen Nordsee untersuchen Wissenschaftler, wie ökologische Prozesse im bedrohten „Lebensraum Wattenmeer”︁ ablaufen
Transposon vectors for gene‐trap insertional mutagenesis in vertebrates
Authors: Clark Karl J. , Geurts Aron M. , Bell Jason B. , Hackett Perry B.
Published: July 2004

The function of most vertebrate genes remains unknown or uncertain. Insertional mutagenesis offers one approach to identify and understand the function of these genes. Transposons have been used successfully in lower organisms and plants for insertional mutagenesis, but until activation of the Sleeping Beauty (SB) transposon system, there was no indication of active DNA‐based transposons in vertebrates. Investigator‐driven insertional mutagenesis in vertebrates has relied on retroviral insertions or selection of low‐frequency integration of naked DNA in ES cell lines. We have combined the highly active SB transposon with gene‐trapping technology to demonstrate that transposon traps can be used for insertional mutagenesis screens in vertebrates. In our studies about one‐fourth of the trap insertions appear to be in transcriptional units, a rate that is commensurate with random integration. We show that gene‐traps coupled to a fluorescent protein reporter gene can be used to detect insertions into genes active in specific cells of living zebrafish embryos, supporting use of our transposon traps for high‐throughput functional genomic screens in vertebrates. genesis 39:225–233, 2004. © 2004 Wiley‐Liss, Inc.
Refining GAL4‐driven transgene expression in Drosophila with a GAL80 enhancer‐trap
Authors: Suster Maximiliano L. , Seugnet Laurent , Bate Michael , Sokolowski Marla B.
Published: July 2004

We constructed an enhancer‐trap element, P{GAL80}, that encodes the yeast GAL80 repressor to refine expression of transgenes driven by the binary GAL4/UAS system. GAL80 blocks GAL4 activity by binding to its transcriptional activation domain. We screened GAL80 enhancer‐traps for repression of GAL4‐induced green fluorescent protein (GFP) in the intact larval nervous system. We selected one line that repressed GFP in a large set of cholinergic neurons. This line was used to refine GFP expression from a set of over 200 neurons to a subset of 20 neurons in a preselected GAL4 line. Expression of tetanus neurotoxin, a potent blocker of neurotransmitter release, in these 20 neurons reproduced an aberrant larval turning behavior previously assigned to the parental set of 200 neurons. Our results suggest that targeted GAL80 expression could become a useful means of spatially refining transgene expression in Drosophila. genesis 39:240–245, 2004. © 2004 Wiley‐Liss, Inc.
Localization of Swallow‐Green fluorescent protein in Drosophila oogenesis and implications for the role of Swallow in RNA localization
Authors: Stephenson Edwin C.
Published: July 2004

The localization of a hybrid protein composed of swallow and Green Fluorescent Protein (GFP) during Drosophila oogenesis is reported. I constructed a hybrid gene with GFP inserted into an internal position of swallow. This gene was integrated into the Drosophila genome and provides full swallow+ function, as assayed by the complete rescue of strong swallow mutants. Swallow‐GFP is localized at all points along the oocyte cortex from vitellogenic stages of oogenesis through the end of oogenesis. Higher concentrations of swallow‐GFP are present at the anterior oocyte cortex than at the lateral and posterior oocyte cortices at Stages 10 and 11, when bicoid and htsN4 mRNA transport from nurse cells and localization in the oocyte are most active. At Stage 9 and at Stages 12–14 swallow‐GFP is equally distributed at the anterior, lateral, and posterior oocyte cortices. The position of swallow‐GFP in vitellogenic stages is identical to the position of endogenous swallow protein determined by indirect immunofluorescence using an anti‐swallow antibody. At the oocyte cortex, swallow‐GFP is present in particulate structures that lie within or just internal to the dense cortical actin meshwork. These particles show little or no movement, suggesting that they are attached to or embedded in the oocyte cortex. These observations are most easily interpreted in the context of mRNA anchoring or microtubule organizing functions for the swallow protein. genesis 39:280–287, 2004. © 2004 Wiley‐Liss, Inc.
On Minnesang in the Database
Authors: Schlechter Armin , Zimmermann Karin , Miller Matthias
Published: July 2004

The mediaeval German manuscripts at the Heidelberg University Library are cultural and historical records of great significance. Comprehensive cataloguing is making the collection newly accessible for research
An Insect's Life in a Scented World
Authors: Galizia Giovanni
Published: July 2004

Whether searching for food or a partner — scent plays an important role for insects. How scents are processed in their brain is answered by studies on the olfactory system in honeybees and robber ants
Rhesus Monkeys and Reproductive Strategy
Authors: Schmidtke Jörg , Nürnberg Peter , Krawczak Michael
Published: July 2004

A male rhesus monkey leaves his birth group to reproduce. On Cayo Santiago, the “Monkey Island” off Puerto Rico, researchers are searching for the gene that controls the primates migratory behaviour
Simultaneous Determination of Plasma Mevalonate and 7 α–Hydroxy–4–Cholesten–3–One Levels in Hyperlipoproteinemia: Convenient Indices for Estimating Hepatic Defects of Cholesterol and Bile Acid Syntheses and Biliary Cholesterol Supersaturation
Authors: Shoda Junichi , Miyamoto Jiro , Kano Masahito , Ikegami Tadashi , Matsuzaki Yasushi , Tanaka Naomi , Osuga Toshiaki , Miyazaki Hiroshi
Published: July 2004

The high prevalence of cholesterol gallstone disease in hypertriglyceridemic patients may be associated with frequent metabolic defects in cholesterol and bile acid syntheses and in the concomitant formation of bile supersaturated with cholesterol. This study had the two aims: (1) to assess whether the defects as well as the degree of biliary cholesterol supersaturation in patients with hyperlipoproteinemia (HLP) can be estimated by the simultaneous determination of plasma mevalonate (MVL) and 7 α–hydroxy–4–cholesten–3–one (C4); and (2) to assess the possible application of an estimated cholesterol saturation index ([CSI]E) as a means of evaluating the clinical effects of simvastatin on biliary lipid composition. Biliary cholesterol supersaturation was observed in patients with both IIa and IV HLP types. Consistent with the high activity and steady–state messenger RNA level of 3–hydroxy–3 methylglutaryl coenzyme A (HMG–CoA) reductase, plasma MVL was significantly higher in 86 patients with HLP (38 type IIa, 44.1 ± 2.4 nmol/L and 48 type IV, 56.7 ± 2.3;

P

< .01) than in 41 normolipidemic subjects (34.2 ± 1.5), closely correlating with the molar percentage of cholesterol in bile (

r

= .61,

P

= .0001; n = 86). On the other hand, consistent with the high activity and messenger RNA level of cholesterol 7 α–hydroxylase, plasma C4 was significantly higher in patients with HLP (type IIa, 28.8 ± 2.3 nmol/L and type IV, 38.3 ± 2.7;

P

< .01) than in normolipidemic subjects (17.4 ± 1.5). Plasma C4 was closely correlated with plasma MVL (

r

= .40,

P

= .0001; n = 86), but was inversely correlated with the molar percentage of bile acids in bile (

r

= .49,

P

= .0001; n = 86). Assuming that cholesterol supersaturation in patients with HLP may be governed by both an enhanced cholesterol secretion (closely reflected by plasma MVL) and a decreased secretion of bile acids (closely reflected by plasma C4), the multivariate linear regression–analyses revealed that an index defined as estimated CSI ([CSI]E) (%) in patients with HLP was given by the following equation using plasma MVL and C4 (nmol/L): [CSI]E = 1[MVL] + 0.7[C4] + 44.4. Biliary cholesterol supersaturation in patients treated with simvastatin improved in a manner parallel to the time course of decreases in plasma MVL and C4. The [CSI]E before and at the end of treatment were correlated with biliary CSI. These results indicate that defects of hepatic cholesterogenesis, and bile acid synthesis, and the degree of biliary cholesterol supersaturation in patients with HLP can be estimated exactly by the simultaneous determination of plasma MVL and C4; furthermore [CSI]E may be adopted for clinical use as a convenient index of biliary CSI.
In Situ Nucleic Acid Hybridization of Pyruvate Dehydrogenase Complex–E2 in Primary Biliary Cirrhosis: Pyruvate Dehydrogenase Complex–E2 Messenger Rna Is Expressed in Hepatocytes But Not in Biliary Epithelium
Authors: Harada Kenichi , Van de Water Jarada , Leung Patrick S.C. , Coppel Ross L. , Nakanuma Yasuni , Gershwin Mevvill Eric
Published: July 2004

Pyruvate dehydrogenase–E2, or a cross–reactive molecule, has been shown by a variety of immunohistochemical methods to be present in increased amounts in biliary epithelial cells (BEC) in primary biliary cirrhosis (PBC). In this study, to further understand the nature of the immunoreactive molecule in BEC, we examined the expression of pyruvate dehydrogenase complex–E2 (PDC–E2) messenger RNA (mRNA) and PDC–E2 protein in sections of livers from patients and controls to help identify the molecule found in BEC. We performed

in situ

hybridization using an antisense probe against the major epitope of PDC–E2. The data were very striking and suggested that there was no increased production of PDC–E2 in BEC. For example, in livers from patients with PBC, PDC–E2 mRNA was found in periportal hepatocytes in 16 of 17 cases (94%). In contrast, interlobular bile ducts and septal bile ducts had detectable levels of PDC–E2 mRNA in only 1 of 17 (6%) and 3 of 8 (38%) cases, respectively. Interestingly, proliferating bile ductules contained detectable levels of mRNA in 12 of 15 cases (80%). In control liver, periportal hepatocytes were positive in 15 of 17 cases (88%). Interlobular bile ducts, septal bile ducts, and proliferating bile ductules expressed mRNA signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectively. When formalin–fixed, paraffin–embedded sections were examined by immunohistochemical staining with anti–PDC–E2 monoclonal antibody (mAb) C355.1, the interlobular bile ducts showed typical aberrant apical staining in all 10 PBC cases, but 0 of 9 liver controls. Periportal hepatocytes, proliferating bile ductules and infiltrating mononuclear cells stained with C355.1 but in a characteristic mitochondrial staining pattern. The presence of a PDC–E2-like molecule recognized by C355.1 is not reflected by the expression levels of PDC–E2 mRNA in the BEC of patients with PBC.
Biliary Secretion of Anionic Polypeptide Fraction Is Not Coupled to That of Phospholipids and Cholesterol in Rats
Authors: Verkade Henkjan J. , Kuipers Folkert , Domingo Nicole , Havinga Rick , Léonardi Jeannie , Vonk Roel J. , Lafont Huguette
Published: July 2004

Anionic polypeptide fraction (APF) is a phospholipid– and calcium–binding apoprotein present in animal and human bile, predominantly associated with cholesterol–phospholipid vesicles. In bile, the protein may play a physiological role in preventing precipitation of calcium salts. APF has also been suggested to be of regulatory importance in the process of biliary lipid secretion. The aim of the present study was to investigate whether the secretion rates of APF and that of biliary lipids are coupled, which would support a physiological role of APF in biliary lipid secretion. Biliary secretion rates of bile acids, phospholipids, and cholesterol were experimentally modulated in three different rat models. Secretion rates of APF were compared with that of bile acids, lipids, and with that of two other biliary proteins, the lysosomal protein β–glucuronidase and apolipoprotein A–I (apo A–I). Model 1: diurnal variation in bile formation during chronic bile diversion; model 2: specific inhibition of biliary phospholipid and cholesterol, but not of bile acid secretion by infusion of the organic anion, sulfated lithocholyltaurine; model 3: acute interruption of the enterohepatic circulation in unanesthetized rats. The diurnal variation in bile formation involved a parallel increase of the biliary secretion rates of bile acids (+56 ± 7%, mean ± SD), phospholipids (+53 ± 29%), cholesterol (+73 ± 54%), and APF (+72 ± 86%) during the night phase of the cycle. Infusion of sulfated lithocholyltaurine inhibited biliary phospholipid and cholesterol secretion (-78 ± 15%, and -54 ± 25%, respectively), but did not affect biliary bile acid or APF secretion rate (-19 ± 14%, and +12 ± 107%, respectively). Within 4 hours after interruption of the enterohepatic circulation, bile secretion rates for bile acids (-92 ± 3%), phospholipids (-74 ± 13%), cholesterol (-64 ± 8%), and APF (-58 ± 24%) rapidly declined to a new steady–state level. Correlation analysis using the data from the three experimental models indicated that the biliary secretion rate of APF was independent from that of phospholipids, cholesterol, β–glucuronidase, and, presumably, apolipoprotein A–I, and positively correlated to bile acid secretion rate and bile flow. The data from three experimental models indicate that the biliary secretion rates of APF and of phospholipids/cholesterol are not coupled and, therefore, do not support a direct physiological role of APF secretion in biliary lipid secretion. APF secretion into bile may, at least partially, be controlled by biliary bile acid secretion.
Total Volume Paracentesis Decreases Variceal Pressure, Size, and Variceal Wall Tension in Cirrhotic Patients
Authors: Kravetz D. , Romero G. , Argonz J. , Guevara M. , Suarez A. , Abecasis R. , Bildozola M. , Valero J. , Terg R.
Published: July 2004

It has been suggested that ascites is a risk factor for variceal bleeding in cirrhotic patients. However, no data of total volume paracentesis (TVP) effects on variceal hemodynamics has yet been published. The aim of this study was to investigate the effects of TVP on variceal pressure, size, and tension in cirrhotic patients. Before sclerotherapy, 18 cirrhotic patients with grade II esophageal varices were studied. The following measurements were performed on 12 patients at basal condition and after TVP: inferior vena cava pressure, esophageal pressure (EP), and intravariceal pressure (IVP) by direct punction and variceal size at endoscopy. The same measurements were performed at basal condition and 1 hour later without TVP on the other 6 patients used as a control group. Variceal pressure gradient (VPG) and variceal wall tension (WT) were calculated. Paracentesis and intra– abdominal pressure were obtained with a direct punction. No demographic differences were observed between both groups. Paracentesis produced a significant reduction of IVP (from 25.6 ± 2.4 to 17.9 ± 2.1 mm Hg, means ± SEM, –30%,

P

< .05), VPG (from 16.6 ± 2.4 to 10.8 ± 1.4 mm Hg, –35%,

P

< .05). TVP also reduced variceal size (from 9 ± 0.3 to 5.6 + 0.4 mm, –38%,

P

< .05) and WT (from 75.3 ± 11.6 to 30 ± 4.7 mm Hg. mm, –60%,

P

< .05). Intra–abdominal pressure decreased from 18 ± 2.2 to 4 ± 0.9 mm Hg (

P

< .05), and IVC decreased from 15.5 ± 2.4 to 5.7 ± 1.5 mm Hg (

P

< .05). No significant differences were observed in mean arterial pressure and heart rate. The mean ascitic fluid removed was 8 ± 0.71 L. No significant difference between measurements was observed in the control group. Our results show that TVP significantly decreases variceal pressure and tension. These results suggest that ascites removal can be useful in the treatment of variceal bleeding in cirrhotic patients.
Beta–Adrenergic Antagonists in the Prevention of Gastrointestinal Rebleeding in Patients With Cirrhosis: A Meta–Analysis
Authors: Bernard B. , Lebrec D. , Mathurin P. , Opolon P. , Poynard T.
Published: July 2004

A meta–analysis of 12 selected randomized trials was performed to assess the efficacy of beta–blockers in the prevention of rebleeding and the effect on long–term survival in patients with cirrhosis. Five end points were assessed: rebleeding, variceal rebleeding, death, death from bleeding, and adverse events. Analyses were performed according to the intention–to–treat method. For each end point, heterogeneity and treatment efficacy were assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to treatment duration, cause of initial bleeding, use of placebo, type of beta–blocker, type of publication, certainty of randomization, severity of cirrhosis, interval between index bleed and randomization, and methodological quality. Beta–blockers significantly increased the mean percentage of patients free of rebleeding (21% mean improvement rate, CI 95%: 10%–32%,

P

< .001, relative risk 1.42), the mean percentage of patients free of variceal rebleeding (20% mean improvement rate, CI 95%: 11%–28%,

P

< .001), the mean survival rate (5.4% mean improvement rate, CI 95%: 0%–11%,

P

= .05, relative risk 1.27), the mean percentage of patients free of bleeding death (7.4%, CI 95%: 2%–13%,

P

< .01, relative risk 1.50). Five patients would need to be treated with beta–blockers to prevent one rebleeding episode, 14 treated to prevent one death, and 13 treated to prevent one death from bleeding. There was no significant heterogeneity among studies by both methods of analysis. In patients with esophageal varices, beta–blockers significantly increase the mean percentage of patients free of rebleeding and the mean survival rate at 2 years.
Endoscopic Variceal Ligation Is Superior to Combined Ligation and Sclerotherapy for Esophageal Varices: A Multicenter Prospective Randomized Trial
Authors: Saeed Z. A. , Stiegmann G. V. , Ramirez F. C. , Reveille R. M. , Goff J. S. , Hepps K. S. , Cole R. A.
Published: July 2004

Patients who have bled from varices remain at risk for rebleeding. There is interest in methods that would enable rapid eradication of varices. The present trial was designed to study whether combining ligation with sclerotherapy will allow quicker eradication of varices than either modality alone. Patients with bleeding esophageal varices were randomized into ligation or combination therapy groups. Patients in the ligation group were treated with endoscopic rubber band ligation alone. In combination group patients, each variceal column was ligated distally and 1 mL of ethanolamine was injected proximal to each ligated site. Subsequent treatment sessions were at 7– to 14–day intervals until varices were eradicated. The clinical and endoscopic characteristics of 25 patients in the ligation group were similar to those of 22 patients in the combination group. Follow–up was up to 30 months. Active bleeding was controlled in 100% of patients in the ligation group and 75% of those in combination group (

P

= NS). It took 3.3 ± .4 (range, 1–7) sessions to eradicate varices with ligation and 4.1 ± .6 (1–7) with combination therapy (

P

= NS). Survival (four deaths in ligation group, 8 in combination group), rebleeding rate (25% vs. 36%), and varix recurrence (16% vs. 23%) also were similar. There were more complications with combination therapy, including deep ulcers (65% vs. 20%;

P

< .05); dysphagia (30% vs. 0%;

P

< .05), with three strictures requiring dilation; and pain (30% vs. 10%;

P

= NS). Our results show that sclerotherapy combined with ligation offers no benefit over ligation alone. The higher complication rate with combination therapy does not warrant this approach.
Cytoprotection by Fructose and Other Ketohexoses During Bile Salt–Induced Apoptosis of Hepatocytes
Authors: Zeid I. M. , Bronk S. F. , Fesmier P. J. , Gores G. J.
Published: July 2004

Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt– induced necrosis, the effect of fructose on bile salt–induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt–induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)–induced apoptosis in a concentration–dependent manner with a maximum inhibition of 72% ± 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to <25% of basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8), which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually potentiated apoptosis 1.6–fold. Fructose cytoprotection also could not be explained by induction of bcl–2 transcription or metal chelation. Because we could not attribute fructose cytoprotection to metabolic effects, alterations in the expression of bcl–2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt–induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt–induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose–sensitive pathways appear to initiate both bile salt–induced cell apoptosis and necrosis, whereas dissimilar, pH–sensitive, effector mechanisms execute these two different cell death processes.
Increased Circulating Transforming Growth Factor β1 in A Patient With Giant Hepatic Hemangioma: Possible Contribution to An Impaired Immune Function
Authors: Ito N. , Kawata S. , Tsushima H. , Tamura S. , Kiso S. , Takami S. , Igura T. , Monnden M. , Matsuzawa Y.
Published: July 2004

A patient, having a huge hepatic hemangioma, presented with decreases in the number of peripheral lymphocytes and in serum concentrations of γ–globulin and immunoglobulin (Ig) G, and a negative purified protein derivatives skin test, indicating that the patient's immunity was impaired. The plasma concentration of transforming growth factor β1 (TGF–β1), a potent immunosuppressor, in the patient was markedly elevated (113 ng/mL, normal < 5). After the surgical removal of the tumor, the plasma TGF–β1 concentration decreased, and the patient's immunity was restored to normal. Northern blot analysis showed an overexpression of the TGF–β1 gene in the hemangioma tissue, while normal control liver tissue expressed undetectable levels of TGF–β1 messenger RNA. These results suggest that the elevated levels of TGF–β1 in the plasma were derived from the giant hemangioma tissue and may have contributed to the impaired immune function in the patient.
Hepatic Amyloidosis: Clinical Appraisal in 77 Patients
Authors: Gertz M. A. , Kyle R. A.
Published: July 2004

The purpose of this study was to assess prognostic factors and survival in patients with liver involvement in immunoglobulin light–chain amyloidosis. Comparisons were made with other patients with immunoglobulin light–chain amyloidosis who did not have liver involvement. A total of 77 consecutively seen patients were evaluated: 19 had hepatic amyloidosis and 58 had amyloidosis without liver involvement. Eighteen of 19 patients with liver amyloidosis could be histologically diagnosed without needle biopsy of the liver. All but 2 had a detectable free light chain in the serum or urine, distinguishing this from other infiltrative liver processes. Patients with liver amyloid had significantly higher alkaline phosphatase levels and C–reactive protein levels compared with patients without hepatic amyloid. The majority of patients had extrahepatic involvement predominantly in the kidney (47%) or heart (42%). The presence of hyposplenism was not a good screening test for the presence of hepatic amyloid. Seven of 19 patients responded to chemotherapy with objective regressions of the clinical manifestations of renal, hepatic, or cardiac involvement. We conclude that the survival of patients with liver involvement in amyloidosis is no different than other patients with amyloidosis. This results from the high proportion of patients having associated renal or cardiac involvement. Most patients can be diagnosed without a liver biopsy when a monoclonal protein is found in the serum or urine. Serum albumin and C–reactive protein levels appear to distinguish patients with liver involvement from those without.