bluuebunny/crossref_metadata_2025 huggingface dataset:
PubNet: a flexible system for visualizing literature derived networks
Authors: Douglas Shawn M , Montelione Gaetano T , Gerstein Mark
Published: August 2005

We have developed PubNet, a web-based tool that extracts several types of relationships returned by PubMed queries and maps them into networks, allowing for graphical visualization, textual navigation, and topological analysis. PubNet supports the creation of complex networks derived from the contents of individual citations, such as genes, proteins, Protein Data Bank (PDB) IDs, Medical Subject Headings (MeSH) terms, and authors. This feature allows one to, for example, examine a literature derived network of genes based on functional similarity.
Phase II Multi-Institutional Randomized Trial of Docetaxel Plus Cisplatin With or Without Fluorouracil in Patients With Untreated, Advanced Gastric, or Gastroesophageal Adenocarcinoma
Authors: Ajani Jaffer A. , Fodor Miguel B. , Tjulandin Sergei A. , Moiseyenko Vladimir M. , Chao Yee , Filho Sebastiao Cabral , Majlis Alejandro , Assadourian Sylvie , Van Cutsem Eric
Published: August 2005

Purpose

The purpose of this study was to define the contribution of docetaxel to combination chemotherapy in the outcome of patients with advanced gastric or gastroesophageal adenocarcinoma. We compared the overall response rate (ORR) and safety of docetaxel plus cisplatin (DC) with DC plus fluorouracil (DCF) to select either DC or DCF as the experimental treatment in the ensuing phase III part of trial V-325.

Patients and Methods

In this phase II randomized study, untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received either DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5) or DC (docetaxel 85 mg/m2 and cisplatin 75 mg/m2 on day 1) every 3 weeks. An independent data monitoring committee (IDMC) was to select one of the two regimens based primarily on ORR and safety profile.

Results

Of 158 randomly assigned patients, 155 (DCF, n = 79; DC, n = 76) received treatment. The confirmed ORR was 43% for DCF (n = 79) and 26% for DC (n = 76). Median time to progression was 5.9 months for DCF and 5.0 months for DC. Median overall survival time was 9.6 months for DCF and 10.5 months for DC. The most frequent grade 3 and 4 events per patient included neutropenia (DCF = 86%; DC = 87%) and GI (DCF = 56%; DC = 30%).

Conclusion

Both regimens were active, but DCF produced a higher confirmed ORR than DC. Toxicity profiles of DCF were considered manageable. The IDMC chose DCF for the phase III part of V-325, which compares DCF with cisplatin plus fluorouracil.
Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells
Authors: Wiblin Anne E. , Cui Wei , Clark A. John , Bickmore Wendy A.
Published: August 2005

Nuclear organisation is thought to be important in regulating gene expression. Here we investigate whether human embryonic stem cells (hES) have a particular nuclear organisation, which could be important for maintaining their pluripotent state. We found that whereas the nuclei of hES cells have a general gene-density-related radial organisation of chromosomes, as is seen in differentiated cells, there are also distinctive localisations for chromosome regions and gene loci with a role in pluripotency. Chromosome 12p, a region of the human genome that contains clustered pluripotency genes including NANOG, has a more central nuclear localisation in ES cells than in differentiated cells. On chromosome 6p we find no overall change in nuclear chromosome position, but instead we detect a relocalisation of the OCT4 locus, to a position outside its chromosome territory. There is also a smaller proportion of centromeres located close to the nuclear periphery in hES cells compared to differentiated cells. We conclude that hES cell nuclei have a distinct nuclear architecture, especially at loci involved in maintaining pluripotency. Understanding this level of hES cell biology provides a framework within which other large-scale chromatin changes that may accompany differentiation can be considered.
Quantitative analysis of changes in spatial distribution and plus-end geometry of microtubules involved in plant-cell cytokinesis
Authors: Austin Jotham R. , Seguí-Simarro José M. , Staehelin L. Andrew
Published: August 2005

The cell plate of higher plants is formed within a ribosome-excluding cell plate assembly matrix. Phragmoplast microtubules facilitate cell-plate formation by forming a scaffold that directs Golgi-derived vesicles to the forming cell plate. Here, we analyse the effects of the cell-plate assembly matrix on phragmoplast microtubule plus-end geometry by electron tomography of cryogenically fixed Arabidopsis meristem cells. Five distinct microtubules plus-end geometries are seen - blunt, extended, horned, flared and hybrid extended/horned. We have quantified and mapped these types of plus-end morphology during the different stages of cell-plate formation and analysed the effects of cell-plate assembly matrix association on microtubule plus-end morphologies. Our results show that somatic-type phragmoplast microtubules do not interdigitate at the cell plate mid-line. The cell-plate assembly matrix is shown to stabilize microtubule plus ends, as evidenced by the fact that of these microtubules that do not terminate in such a matrix, 40-80% are horn-shaped (shrinking), whereas of those that end in such a matrix, 50-70% are blunt (metastable). Also, a third of the blunt-ended microtubules within the cell-plate assembly matrix end at a distance of ∼30 nm from the cell plate.
Contribution of sequence variation inDrosophilaactins to their incorporation into actin-based structures in vivo
Authors: Röper Katja , Mao Yanlan , Brown Nicholas H.
Published: August 2005

Actin is a highly conserved protein important for many cellular functions including motility, contraction in muscles and intracellular transport. Many eukaryotic genomes encode multiple actin protein isoforms that differ from each other by only a few residues. We addressed whether the sequence differences between actin paralogues in one species affect their ability to integrate into the large variety of structures generated by filamentous actin. We thus ectopically expressed all six Drosophila actins as fusion proteins with green fluorescent protein (GFP) in a variety of embryonic, larval and adult fly tissues. We found that each actin was able to integrate into most actin structures analysed. For example, in contrast to studies in mammalian cells, the two Drosophila cytoplasmic actins were incorporated into muscle sarcomeres. However, there were differences in the efficiency with which each actin was incorporated into specific actin structures. The most striking difference was observed within the Z-lines of the sarcomeres: one actin was specifically excluded and we mapped this feature to one or both of two residues within the C-terminal half of the protein. Thus, in Drosophila, the primary sequence of different actins does affect their ability to incorporate into actin structures, and so specific GFPactins may be used to label certain actin structures particularly well.
αvβ3-integrin-dependent activation of focal adhesion kinase mediates NF-κB activation and motogenic activity by HIV-1 Tat in endothelial cells
Authors: Urbinati Chiara , Bugatti Antonella , Giacca Mauro , Schlaepfer David , Presta Marco , Rusnati Marco
Published: August 2005

Once in the extracellular environment, the transactivator protein HIV-1 Tat exerts several pleiotropic effects by interacting with different cellular receptors, including integrin αvβ3. Real-time surface plasmon resonance analysis reveals that Tat/αVβ3 interaction occurs with rapid kinetics (association and dissociation rates equal to 1.16×107 M-1 s-1 and 3.78×10-1 s-1, respectively) and high affinity (dissociation constant = 32 nM). Through this interaction, substratum-immobilized Tat promotes adhesion and motogenic activity in endothelial cells. Also, αvβ3/Tat interaction triggers the activation of focal adhesion kinase, RhoA and pp60src. Overexpression of the dominant negative form of focal adhesion kinase, but not of an inactive Leu1034Ser substitution mutant isoform, impairs the activation of focal adhesion kinase and RhoA, but not that of pp60src, without affecting endothelial cell adhesion and spreading. αvβ3/Tat interaction triggers the activation of NF-κB in endothelial cells in a focal adhesion kinase-, RhoA- and pp60src-dependent manner, as shown in dominant negative focal adhesion kinase transfectants or using specific pharmacological inhibitors. Finally, the activation of focal adhesion kinase, RhoA, NF-κB and pp60src are required to mediate the motogenic activity of Tat in endothelial cells.

Since Tat accumulates in an immobilized form in the extracellular matrix, these results provide new biochemical and biological insights about αvβ3/Tat interaction exploitable for the design of anti-Tat strategies.
Evidence for the presence of a low-mass β1 integrin on the cell surface
Authors: Meng Xiaobo , Cheng Keding , Krohkin Oleg , Mould A. Paul , Humphries Martin J. , Ens Werner , Standing Kenneth , Wilkins John A.
Published: August 2005

Although the cell line K562 reportedly expresses a single species of β1 integrin, α5β1, surface staining with monoclonal antibodies JB1A, 12G10 and B3B11 to the β1 chain clearly demonstrated differences in the expression levels of the epitopes detected by these antibodies. The present studies were initiated to determine the basis for this molecular heterogeneity in the integrins. Cross-linking of surface integrins with B3B11 caused their selective aggregation. This distribution was similar to that observed for the α5 chain. In contrast, cross-linking the β1 chains with 12G10 did not cause codistribution of α5, suggesting that these two species were not associated on the cell surface. Immunoprecipitates of the surface integrins of K562 cells indicated the presence of 120 and 140 kDa forms of the β1 chain which were detected by 12G10 and B3B11, respectively. Immunological, biochemical and mass spectrometric analysis of K562 surface integrins also failed to demonstrate the presence of any α chain in association with the 120 kDa species of β1 of K562 cells. Treatment of the two forms of β1 with PGNase reduced their masses to ∼90 kDa, suggesting that N-glycosylation was responsible for the mass differences. Collectively, these results provide evidence for a novel species of β1 on the cell surface, which does not appear to be associated with any α chain. The data also suggest that differences in glycosylation may be involved in defining the association between the integrin α and β chains and the functional properties of these integrins.
A novel dileucine lysosomal-sorting-signal mediates intracellular EGF-receptor retention independently of protein ubiquitylation
Authors: Tsacoumango Amy , Kil Song Jae , Ma Liping , Sönnichsen Frank D. , Carlin Cathleen
Published: August 2005

One of the main goals of this study was to understand the relationship between an epidermal growth factor (EGF) receptor dileucine (LL)-motif (679-LL) required for lysosomal sorting and the protein ubiquitin ligase CBL. We show that receptors containing 679-AA (di-alanine) substitutions that are defective for ligand-induced degradation nevertheless bind CBL and undergo reversible protein ubiquitylation similar to wild-type receptors. We also demonstrate that 679-LL but not CBL is required for EGF receptor downregulation by an endosomal membrane protein encoded by human adenoviruses that uncouples internalization from post-endocytic sorting to lysosomes. 679-LL is necessary for endosomal retention as well as degradation by the adenovirus protein, and is also transferable to reporter molecules. Using NMR spectroscopy, we show that peptides with wild-type 679-LL or mutant 679-AA sequences both exhibit α-helical structural propensities but that this structure is not stable in water. A similar analysis carried out in hydrophobic media showed that the α-helical structure of the wild-type peptide is stabilized by specific interactions mediated by side-chains in both leucine residues. This structure distinguishes 679-LL from other dileucine-based sorting-signals with obligatory amino-terminal acidic residues that are recognized in the form of an extended β or β-like conformation. Taken together, these data show that 679-LL is an α-helical stabilizing motif that regulates a predominant step during lysosomal sorting, involving intracellular retention under both sub-saturating and saturating conditions.
High-Resolution Time-of-Flight Spectra Obtained Using the MULTUM II Multi-Turn Type Time-of-Flight Mass Spectrometer with an Electron Ionization Ion Source
Authors: Okumura Daisuke , Toyoda Michisato , Ishihara Morio , Katakuse Itsuo
Published: August 2005

This paper describes experiments demonstrating the high mass-resolving power of the MULTUM II multi-turn type time-of-flight (ToF) mass spectrometer with a 1.308-meter circuit controlled by four toroidal electric sector fields1 and an electron ionization (EI) ion source. A mass resolution of 250,000 [full-width at half maximum: (FWHM)] was obtained for N2+ after a flight time of 9.0 ms (flight cycles: 1200, flight length: 1500 m). A doublet of 12C5H514N and 13C12C5H6 ( m/Δ m = 9746; Δ m: mass difference of doublet, m: mass of lighter ion of doublet) was separated and a mass resolution of 91,000 (FWHM) was obtained. A doublet of CDCl2 and CH2Cl2 ( m/Δ m = 54,162) was also separated. A mass resolution of 115,000 (FWHM) was then achieved. When one peak of these doublets was used as a calibrant, the mass of the other peak was determined within a few ppm by mass difference. The ToF depending on the square of m/z was significantly larger than the systematic errors in the ToF, so that good mass accuracy was obtained by one-point mass determination.
Identification of Phosphorylcholine-Substituted Peptides by Their Characteristic Mass Spectrometric Fragmentation
Authors: Grabitzki Julia , Sauerland Volker , Geyer Rudolf , Lochnit Günter
Published: August 2005

Phosphorylcholine (PC)-substituted biomolecules are wide-spread, highly relevant antigens of parasites, since this small hapten has been found to be a potent immunomodulatory component which allows the establishment of long lasting infections of the host. Structural data, especially of protein bound PC-substituents, are still rare due to the observation that mass spectrometric analyses are mostly hampered by this zwitterionic substituent resulting in low sensitivities and unusual but characteristic fragmentation patterns. Here, we investigated the fragmentation behavior of synthetic PC-substituted peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization ion-trap mass spectrometry. We could show that the predominant neutral loss of a trimethylamine unit (Hoffmann elimination) leads to cyclic phosphate derivatives which prevent further fragmentation of the peptide backbone by stabilizing the positive charge at this particular side chain. Knowledge of this PC-specific fragmentation might help to identify PC-substituted biomolecules and facilitate their structural analysis.
A Tandem Mass Spectrometric Approach for Determining the Structure of Molecular Species of Ceramide in the Marine Sponge, Haliclona Cribricutis
Authors: Tilvi Supriya , Majik Mahesh , Naik C.G.
Published: August 2005

Ceramides are important intracellular second messengers that play a role in the regulation of cell growth, differentiation and programmed cell death. Analysis of these second messengers requires a sensitive and specific analytical method to detect individual ceramide species and to differentiate between them. Eight molecular species of ceramide were identified from the marine sponge Haliclona cribricutis using electrospray ionization tandem mass spectrometry (ESI-MS/MS). From this marine sponge, N-hencicosanoyl (N21:0) to N-hexasanoyl (N26:0) octadecasphing-4 (E)-enine have been reported for the first time. The ESI-MS spectra gave several strong protonated [M+H]+ molecular ions with the corresponding bis (2-ethyl hexyl) phthalate adduct [M+H+DHEP]+. The collision-induced dissociation on ceramides at m/z 622.7337, 636.7645, 650.7789, 664.7925 and 678.8130 conducted at low-collision energy produced product ions with good characteristic at m/z 252.31, 264.32, 278.33, 282.33 and 296.35 for d18: 1 sphingosine, regardless of the length of the fatty chain. The MS/MS of the phthalate adduct [M+H+DHEP]+ at m/z 1013.1820, 1027.1971, 1041.2176, 1055.2394 and 1069.2573 also yielded characterizing product ions for sphingosine and confirmed the molecular ion at m/z 391 for bis (2-ethyl hexyl) phthalate. The major ions in the [M+H]+ and [M+H+DHEP]+ were due to neutral loss of [M+H–H2O]+ and [M+H–(H2O)2]+.
Micro-Synthesis and Electron Ionization Mass Spectral Analysis of O-Alkyl N,N-Dialkylphosphoramidocyanidates
Authors: Gupta Arvind. K. , Palit Meehir , Pardasani Deepak , Shakya Purushottam , Srivastava Rajendra K. , Dubey Devendra K.
Published: August 2005

This communication describes the microsynthesis and gas chromatographic/mass spectrometric (GC/MS) analysis of O-alkyl N,N-dialkylphosphoramidocyanidates (ADAPCs), which are analogs of the chemical warfare agent, Tabun. The study was undertaken with a view to develop a spectral database of ADAPCs for verification purposes of the Chemical Weapons Convention (CWC). Reported microsynthetic approaches have advantages over traditional synthesis in terms of efficiency, synthetic waste and exposure to toxic chemicals. GC/MS analysis of a variety of these compounds (ADAPCs) was performed. Based on the obtained mass spectra of structurally diverse ADAPCs, the fragmentation routes are proposed, which explains most of the characteristic ions.
Electrospray Ionization Tandem Mass Spectrometry Investigation of the Polymerization of Tetrahydrofuran Initiated by Phosphorus Oxychloride
Authors: Zhou Gui-Ji , Xu Peng-Xiang , Yeb Yong , Zhao Yu-Fen
Published: August 2005

Phosphorus oxychloride was found to induce ring opening of tetrahydrofuran (THF) to synthesize THF oligomer incorporated phosphate. Electrospray ionization multi-stage tandem mass spectrometry was used to study the products and confirm the structures.
The Generation of Neutral Derivatives of Low-Valence Iron, RFe(I), by Netralization—Reionization Mass Spectrometry
Authors: Zagorevskii Dmitri
Published: August 2005

Neutralization–reionization mass spectrometry is applied for the generation of low-valence iron derivatives. Neutralization of RFe+ (R = H, F, Cl, Br, I, CN, OH, NH2, acac, C6H5) ions resulted in the corresponding neutrals having lifetimes of at least 5 μs. Atom connectivities in RFe ions and neutrals were elucidated by a variety of tandem mass spectrometry techniques. The present study provides the first experimental evidence of the intrinsic stability of neutral IFe, NCFe, acacFe and C6H5Fe.
Analysis of Benzylisoquinoline-Type Alkaloids by Electrospray Tandem Mass Spectrometry and Atmospheric Pressure Photoionization
Authors: Schmidt Jürgen , Raith Klaus , Boettcher Chotima , Zenk Meinhart H.
Published: August 2005

Benzylisoquinoline alkaloids found in the Papaveraceae family play a major role in pharmaceutical biology. This is the first systematic study dealing with electrospray tandem mass spectrometry (ESI-MS/MS) of all benzylisoquinolines found as biogenetic precursors of morphinan alkaloids. Tandem mass spectral data are presented for norlaudanosoline, laudanosoline, 4′- O-methyl-norlaudanosoline, 6- O-methyl-norlaudanosoline, norcoclaurine, coclaurine, N-methylcoclaurine, N-methyl-3′-hydroxycoclaurine, N-methyl-3′- O-methylcoclaurine, norreticuline and reticuline. This study compares results obtained using an ion trap mass spectrometer with those obtained using a triple quadrupole one. The results highlight the differences between the tandem-in-time versus the tandem-in-space principle, often hampering the development of ESI-MS/MS libraries. In addition, the use of the atmospheric pressure photoionisation technique for the analysis of such substances is discussed.
Origin Differentiation of a Heroin Sample and its Acetylating Agent with 13C Isotope Ratio Mass Spectrometry
Authors: Zhang Daming , Sun Wei , Yuan Zengping , Ju Huangxian , Shi Xuejun , Wang Chonghu
Published: August 2005

A novel method for deducing the origins of heroin and the reagent used for acetylization was established based on δ13C determinations of heroin and its hydrolysate, morphine, using gas chromatography 13C isotope ratio mass spectrometry (GC-C-IRMS). The alkaline and acid hydrolysis conditions of heroin were optimized. Both yield and purity of morphine produced could meet the requirement for a GC-C-IRMS analysis. Using (2-diethylaminoethyl-2,2- diphenylvalerate) as internal standard the determinations of heroin and morphine contents were performed with a GC method in a linear range of 0.2 to 2.0 mg mL−1 that was required to gain the isotope ratio results. The hydrolysis and synthesis of heroin did not change the δ13C value of morphine. The precision for δ13C detection of both heroin and morphine was sufficient for origin differentiation of heroin samples. The information about the origins of acetylation regents could be deduced from the difference of δ13C values between heroin and morphine. The results for origin differentiation of ten heroin samples grouped into different regions and their acetylating agents were satisfactory.
Search for Melanoma Markers in Plasma and Serum Samples
Authors: Seraglia Roberta , Vogliardi Susanna , Allegri Graziella , Comai Stefano , Lise Mario , Rossi Carlo Riccardo , Mocellin Simone , Scalerta Romano , Ragazzi Eugenio , Traldia Pietro
Published: August 2005

Fourteen blood samples from patients with melanomas and 11 blood samples from healthy subjects were analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The study focussed on species of low molecular weight, in the 800–5000 Da range, present in plasma and sera. While for healthy subjects plasma samples lead to the production of a higher number of ionic species, for melanoma patients a high number of diagnostic ions, present with high frequency and with quite high relative abundance, are present, in particular, in serum samples and, to a lesser extent, also in plasma. Since plasma samples are obtained more easily in comparison to sera, it is possible to suggest that plasma can also be used for these studies.
Formation and Reactions of Clusters in the Gas Phase: Small Peptides and Carboxylic Acids
Authors: Rahman Osama Abdel , Grotemeyer Jürgen
Published: August 2005

The cluster formation of 17 small dipeptides with different primary structures and vanillic acid was investigated by means of a neutral laser desorption and supersonic beam expansion followed by multi-photon ionization time of flight mass spectrometry. The structures of these clusters have been characterized by mass spectrometric methods as well as by density functional theory calculations. It shows that the structure of the cluster from a dipeptide and vanillic acid is described by a hydrogen bond between the phenolic group of the vanillic acid and the N-terminal amino function of the dipeptide. The intensity of the cluster ion and the main fragmentation product, the protonated peptide ion, can be linked to the proton affinity of the peptide. Furthermore, the fragmentation reactions of the protonated peptide are accompanied by extensive hydrogen rearrangements yielding both a and y fragments. The intensities of these fragments follow the proton affinity of the dipeptide.
Soft Deposition of Organic Macromolecules with Fast Atom Bombardment Mass Spectrometry
Authors: Yang X. , Räder H.J. , Rouhanipour A. , Müllen K.
Published: August 2005

In order to investigate the requirements for soft deposition of intact positively charged organic macromolecules, an homogenous series of modal compounds such as polyphenylene dendronized perylenes (PDPs), C80H52, C200H132 and C320H212 and a series of derivatives involving perylene derivative, C98H104N8O4, terrylene derivative, C78H82N6O4 and quaterrylene derivative, C140H138N10O8, were used for soft-landing experiments on a metallic or matrix coated surface using fast atom bombardment mass spectrometry. Soft-landing can be achieved at impact energies below 180 eV with no production of fragments. The deposition rate shows strong energy dependence with similar behavior of the different organic compounds. A single isotope of the molecule was selected and soft-landed at increased resolution.
Parameter Analysis on Stability of a Suspendome
Authors: Chen Zhi-Hua , Li Yang
Published: August 2005

As a kind of hybrid space structures, the suspendome system increases the stiffness and improves the stability of the original dome system by the appropriate use of prestressing cables. Based on the engineering application of suspendome in Tianbao Center (completed in China, 2002), the present paper concentrates on the stability performance of the suspendome with a span of 35.4m using different structural parameters, including the rise-span ratio, magnitude and level settings of initial prestressing in cables, connection rigidity and boundary support condition. Stability performances including buckling mode, critical loads and sensitivity to initial geometric imperfection are studied in detail, and contrast analyses with the corresponding singly-layer shells are carried out to study the superiorities of the suspendome over the single-layer shell. Some valuable conclusions are drawn for practical design.
Buckling Load of Elliptic Paraboloidal Single Layer Reticulated Roofs under Uniform Load
Authors: Kato Shiro , Yamauchi Yoshiro , Ueki Takashi
Published: August 2005

The present paper discusses buckling strength of elliptic paraboloidal reticular roofs under a uniform load on a rectangular plan. The roofs are assumed as three way single layers with a pin-support at all peripheries on a rectangular plan. The buckling analyses are performed for linear buckling, elastic buckling and elastic-plastic buckling. The results of buckling loads are formulated based on two procedures for practical design use. One is an explicit but approximate formula for elastic buckling loads using a knock down factor and the other one is an implicit expression for buckling loads interpreted into a column buckling strength in terms of generalized slenderness ratio.
A Study on Pre-Tension Measurement of Membrane Structures
Authors: Zhanjin Sun , Qilin Zhang
Published: August 2005

Compared with the wide application of the membrane structures, the pretension measuring techniques for membrane structures have developed far more slowly. Further studies to search for a high-precision pretension measuring method which is reliable in theory and convenient for operation are not only necessary but also urgent. With the help of the finite element method, two important characteristics, the principles of “Stress Superposition” and “Stiffening Effect of Stress”, are discovered and summarized in this article. The characteristics relate to the relationships between the pretensions of a stretched rectangular membrane with fixed boundaries around, the out-plane displacements at the central point of the membrane and the normal uniform loads applied on the membrane. Based on these two characteristics, a new method to measure the pretensions of membrane structures is proposed, which is called “Numerical Measurement” in this paper. In the final part of the paper, a series of experiments are reported to validate the correctness of the method. The comparisons between the results of the method and those of the experiments are carefully made, which show that the two groups of results agree with each other very well. The results of numerical simulations and experiments prove that our method is a reliable method, and the measuring results are of high precision.
Force Finding Analysis of Hybrid Space Structures
Authors: Zhi-Hong Zhang , Shi-Lin Dong , Tamura Yukio
Published: August 2005

Some aspects of the application of the equilibrium matrix theory in hybrid space structures are discussed in this paper. In hybrid space structures that are composed of cables and bars only, the flexibility distribution of each bar element should be considered at the same time. Otherwise the structure would probably not be tensioned and constructed successfully. A method to obtain the flexibility distribution of cable-bar hybrid structures is presented by using compatibility equations and equilibrium equations at the same time. This is verified by two numerical examples (Example 1 and 2). In hybrid space structures composed of beams, cables and bars another problem exists, namely constructing the equilibrium matrix of two-node beam element. There are 6 or 3 columns for each two-node beam element in the whole equilibrium matrix. In the case of a suspen-dome there are lots of independent self-equilibrated stress modes. However, in a beam-string structure there is only one self-equilibrated stress mode. In order to avoid the combination of many independent self-stress modes a method named local analysis method is proposed in this paper to obtain the initial pre-stress distribution of the beams. A small beam-string structure is to verify this method.
Parametric Equation of Stress Intensity Factor for Tubular K-joints under In-plane Bending Load
Authors: Shao Y. B.
Published: August 2005

Stress intensity factor (SIF) is frequently used by designers to predict the integrity and residual life of a tubular joint containing a surface crack. In this study, a new numerical modelling method for cracked tubular K-joints has been presented. The proposed model has been verified from experimental results to be accurate and reliable in evaluation of the stress intensity factor for any tubular K-joint with a surface crack. Thereafter, parametric study for more than five thousand numerical models of tubular K-joints with a surface crack subjected to balanced in-plane bending load (IPB) has been carried out. A parametric equation to estimate the SIF value of any cracked tubular K-joint under IPB is then proposed based on the computed numerical results. Error analysis has been also carried out and it shows that the proposed equation can provide reliable and accurate estimation of the SIF value for cracked tubular K-joints under IPB.
Levofloxacin-Induced Acute Fulminant Hepatic Failure in a Patient with Chronic Hepatitis B Infection
Authors: Çoban şahin , Ceydilek Bilge , Ekiz Fuat , Erden Esra , Soykan İrfan
Published: August 2005

OBJECTIVE:

To report a case of possible levofloxacin-induced acute fulminant hepatic failure.

CASE SUMMARY:

An unconscious 55-year-old woman was hospitalized with the diagnosis of hepatic encephalopathy. The patient had received levofloxacin 500 mg daily for 10 days because of an upper respiratory infection. Her past medical history revealed hepatitis B surface antigen positivity as an asymptomatic hepatitis B virus carrier for 10 years. After hospitalization, treatment included plasmapheresis and supportive care. The patient's consciousness improved on the second day of treatment. Other etiologies of fulminant hepatic failure were ruled out, suggesting levofloxacin-induced fulminant hepatic failure. Although the patient received supportive treatment, her condition gradually deteriorated and she died 12 weeks after admission to our hospital. An objective causality assessment revealed that the adverse event was possibly related to levofloxacin.

DISCUSSION:

Levofloxacin is widely used because of its broad spectrum of antimicrobial activity. As of August 9, 2005, to our knowledge, only one case of fulminant hepatic failure in relation to levofloxacin has previously been published. We believe that, in our patient, the relationship between levofloxacin and her illness is clear because of the negative results in the etiological studies, the short time between the drug's administration and the development of disease, and the pathologic findings suggestive of drug-induced hepatitis.

CONCLUSIONS:

Clinicians should be aware of the possibility of severe hepatic injury associated with levofloxacin when prescribing this drug.
Outcomes and Costs of Abciximab Versus Eptifibatide for Percutaneous Coronary Intervention
Authors: Coons James C , Seybert Amy L , Saul Melissa I , Kirisci Levent , Kane-Gill Sandra L
Published: August 2005

BACKGROUND:

Patients undergoing percutaneous coronary intervention (PCI) with stent placement are often prescribed glycoprotein IIb/IIIa inhibitors. However, drug selection is often based on clinicians' preference and cost because few studies have directly compared abciximab and eptifibatide.

Objective:

To compare clinical outcomes and total hospital costs of abciximab and eptifibatide in patients undergoing stent placement during PCI in a real-world setting.

METHODS:

A retrospective cohort analysis was conducted of 960 patients administered abciximab or eptifibatide for intracoronary stent placement between 1999 and 2001 at a tertiary care hospital. The primary outcome was bleeding, defined as major, moderate, or minor according to published criteria. Secondary outcomes included in-hospital death, myocardial infarction, revascularization, and the triple composite endpoint of those outcomes, thrombocytopenia, length-of-stay, and total hospital costs. Pearson's χ 2 analysis, Fisher's exact test, and ANOVA were used for statistical analysis.

RESULTS:

The frequency of bleeding complications based on severity was similar between abciximab and eptifibatide: major (2.4% vs 2.8%), moderate (12.4% vs 10.5%), and minor (4.0% vs 3.9%), respectively (p = 0.86). Secondary clinical outcomes were also similar between groups (p > 0.05). Total costs for hospitalization were significantly greater for abciximab compared with eptifibatide ($16 383 ± 6799 vs $14 115 ± 6285; p < 0.001). Drug acquisition costs were also significantly greater for abciximab compared with eptifibatide ($508 ± 159 vs $465 ± 263; p = 0.003).

CONCLUSIONS:

In patients undergoing stent placement during PCI, abciximab and eptifibatide are comparable in terms of safety and effectiveness despite significant differences in hospitalization and acquisition costs.
Microfluidic Device for Rapid (<15 min) Automated Microarray Hybridization
Authors: Peytavi Régis , Raymond Frédéric R , Gagné Dominic , Picard François J , Jia Guangyao , Zoval Jim , Madou Marc , Boissinot Karel , Boissinot Maurice , Bissonnette Luc , Ouellette Marc , Bergeron Michel G
Published: August 2005

Background: Current hybridization protocols on microarrays are slow and need skilled personnel. Microfluidics is an emerging science that enables the processing of minute volumes of liquids to perform chemical, biochemical, or enzymatic analyzes. The merging of microfluidics and microarray technologies constitutes an elegant solution that will automate and speed up microarray hybridization.

Methods: We developed a microfluidic flow cell consisting of a network of chambers and channels molded into a polydimethylsiloxane substrate. The substrate was aligned and reversibly bound to the microarray printed on a standard glass slide to form a functional microfluidic unit. The microfluidic units were placed on an engraved, disc-shaped support fixed on a rotational device. Centrifugal forces drove the sample and buffers directly onto the microarray surface.

Results: This microfluidic system increased the hybridization signal by ∼10fold compared with a passive system that made use of 10 times more sample. By means of a 15–min automated hybridization process, performed at room temperature, we demonstrated the discrimination of 4 clinically relevant Staphylococcus species that differ by as little as a single-nucleotide polymorphism. This process included hybridization, washing, rinsing, and drying steps and did not require any purification of target nucleic acids. This platform was sensitive enough to detect 10 PCR-amplified bacterial genomes.

Conclusion: This removable microfluidic system for performing microarray hybridization on glass slides is promising for molecular diagnostics and gene profiling.
MDRD-Formel und Cystatin C. Verbesserungen zur Erfassung der glomerulären Filtrationsrate? MDRD formula and cystatin C. Improvements in the assessment of the glomerular filtration rate?
Authors: Hofmann Walter
Published: August 2005

Die Bestimmung von Kreatinin im Serum oder Plasma zur Erfassung einer verminderten glomerulären Filtrationsrate (GFR) stellt zum jetzigen Zeitpunkt einen Standard im medizinischen Alltag dar. Wie eine Vielzahl von Untersuchungen der letzten Jahre gezeigt hat, reicht diese Bestimmung aber nicht aus. Einflussgrößen wie Alter, Geschlecht und Muskelmasse erschweren die Interpretation der Messgröße Kreatinin. Die Standardisierung der Methoden und Wahl der Kalibratoren sind darüber hinaus noch nicht zufrieden stellend. Neben den analytischen Problemen ist die diagnostische Sensitivität der Messgröße gerade bei älteren Patienten nicht ausreichend, um eine Niereninsuffizienz ausschließen zu können. Bei noch unauffälliger Kreatininkonzentration kann die GFR unter 60 mL/min/1.73 m2 liegen. Nach den Guidelines der American Kidney Foundation liegt hier bereits eine mittelschwere Niereninsuffizienz vor. Um auf das Problem der nicht erkannten und zunehmenden Zahl von Niereninsuffizienzen aufmerksam zu machen, wurde von der American Kidney Foundation unter Einbeziehung von Alter und Geschlecht eine neue Formel (einfache MDRD-Formel) zur Abschätzung der GFR empfohlen. Diese Formel kann die Einschränkungen der Kreatininbestimmung natürlich nicht eliminieren. Die neu angefachte Diskussion soll den Anstoß dazu geben, auf die Probleme der Messgröße, damit verbundene Rechenformeln und die differenzierte Weitergabe der Ergebnisse an den behandelnden Arzt hinzuweisen. Das Ergebnis sollte für eine GFR unter 60 mL/min/1.73 m2 als Zahlenwert, Filtrationsraten oberhalb 60 mL/min/1.73 m2 sollten hingegen als >60 mL/min/1.73 m2 ausgegeben werden.

Cystatin C als attraktive Alternative sollte trotz höherer Kosten und noch nicht vollständig geklärter Fragestellungen (Schilddrüse, Einflussgrößen) zusätzlich in das Portfolio unserer Untersuchungen aufgenommen werden.
Besteht Bedarf an neuen kardiovaskulären Risikofaktoren? Is there a need for new cardiovascular risk factors?
Authors: von Eckardstein Arnold
Published: August 2005

Die klassischen Risikofaktoren für kardiovaskuläre Erkrankungen haben einen hohen negativen Vorhersagewert, insbesondere in Verbindung mit Scorewerten und Algorithmen, deren Verwendung derzeit in internationalen Konsens-Richtlinien zur primären Prävention dieser Krankheiten befürwortet wird. Da die Kosten im Verhältnis zur geringen Chance, Fälle zu finden, sehr hoch sind, sollten neuartige Risikofaktoren wie C-reaktives Protein, Lipoprotein(a), Homocystein oder genetische Marker nicht wahllos in bevölkerungsweiten Screeningprogrammen eingesetzt werden. Wegen des niedrigen positiven Vorhersagewertes der klassischen Risikofaktoren besteht aber ein klarer Bedarf, die Risikobeurteilung bei Patienten mit hohem und mittlerem Risiko zu verbessern. Dies betrifft 20–25% der Bevölkerung in Deutschland. Diese Personen sind die bevorzugte Zielgruppe für neue Risikofaktoren. Bei Personen mit intermediärem Risiko kann der neue Risikofaktor den Ausschlag geben, ob oder ob nicht mit Blutdruck oder Lipid senkenden Medikamenten behandelt wird. Bei Patienten mit hohem Risiko ergibt sich bei zusätzlichem Vorliegen neuer Risikofaktoren die Motivation zu einer intensivierten Behandlung von Bluthochdruck und Fettstoffwechselstörungen. Beispiele für solche neuen Risikofaktoren sind C-reaktives Protein (CRP), Lipoprotein(a) oder Mikroalbuminurie. Wünschenswert sind neue Risikofaktoren, welche spezifische Behandlungsmodalitäten nach sich ziehen. Dies ist zur Zeit allenfalls für Homocystein der Fall. Letztlich fehlen randomisierte Interventionsstudien, um den klinischen Nutzen neuer Risikofaktoren zu belegen.
Genetische Diagnostik bei mentaler Retardierung Genetic testing for diseases associated with mental retardation
Authors: Rost Imma , Klein Hanns-Georg
Published: August 2005

Mentale Retardierung betrifft etwa 2–3% der Bevölkerung in den westlichen Industrienationen. Eine sorgfältige Anamnese und klinische Untersuchung sind die Voraussetzungen für eine Verdachtsdiagnose und eine sichdaraus ableitende genetische Diagnostik. Genetische Untersuchungen ermöglichen heute eine sichere Diagnose einer Vielzahl von Erkrankungen, die mit einer MR einhergehen. Damit ist auch eine Aussage zu einem eventuellen Wiederholungsrisiko in den betroffenen Familien und gegebenenfalls eine gezielte Frühförderung der erkrankten Kinder möglich. Bei einigen Erkrankungen wie z.B. chromosomalen Strukturaberrationen oder solchen mit einer hohen Neumutationsrate wie der Neurofibromatose 1 kann zur Abschätzung des Wiederholungsrisikos auch eine Untersuchung der Eltern erforderlich sein. Eine genetische Diagnostik sollte wenn möglich im Zusammenhang mit einer genetischen Beratung angeboten werden. Zu den wichtigsten Untersuchungstechniken gehören neben der klassischen Chromosomenanalyse die Fluoreszenz-in-situ-Hybridisierung (FISH) oder Array Comparative Genomic Hybridization (CGH) zum Nachweis von Mikrodeletionen bzw. zur Analyse der chromosomalen Subtelomerregion, die Multicolour-FISH zur Identifizierung von aberrantem chromosomalem Material, Methylierungs-Assays z.B. zum Nachweis von Prader-Willi- oder Angelman-Syndrom, Mikrosatellitenanalysen zur Detektion einer uniparentalen Disomie (UPD), der Southern-Blot und die PCR-Fragmentanalyse zur Längen-Bestimmung von Triple-Repeats sowie die DNA-Sequenzanalyse im Rahmen der Mutationssuche.
Genetische Diagnostik in der pädiatrischen Onkologie Genetic diagnosis in pediatric oncology
Authors: Haas Oskar A.
Published: August 2005

Die Erforschung und Analyse der mit soliden Tumoren und hämatologischen Neoplasien einhergehenden genetischen Veränderungen spielen in der pädiatrischen Onkologie schon seit langem eine sehr wichtige Rolle. Die daraus resultierende Information ist nicht nur für diagnostische und differentialdiagnostische Belange sowie die Grundlagenforschung besonders wertvoll, sondern wird auch in zunehmendem Masse zur Therapiestratifizierung und Therapieüberwachung eingesetzt. In diesem Artikel gebe ich daher einen kurzen Überblick über ältere und neuere Methoden und beschreibe deren diagnostische Wertigkeit in den jeweiligen Zusammenhängen. Das Spektrum dieser Methoden reicht von der konventionellen Zytogenetik über eine Fluoreszenz-in-situ-Hybridisierung (FISH) und vielfältige RNA- und DNA-basierende qualitative und quantitative Polymerasekettenreaktionen (PCR) bis zu RNA- und DNA- basierenden Genom-Microarray-Methoden. Weiterhin präsentiere ich kurz die häufigsten und wichtigsten genetischen Subgruppen von hämatologischen Neoplasien und soliden Tumoren im Kindesalter, zusammen mit ihrer klinischen Bedeutung. Auf Grund ihres unterschiedlichen pathogenetischen Ursprungs unterscheiden sich sowohl die Art und Häufigkeit der im Kindesalter auftretenden Neoplasien als auch die damit assoziierten genetischen Merkmale grundlegend von jenen des späten Erwachsenenalters. Die ausführliche Analyse dieser genetischen Veränderung, speziell von Tumoren und Leukämien im Kindesalter, hilft uns daher nicht nur, die physiologischen und pathophysiologischen Vorgänge, welche zur Tumorentwicklung und -progression beitragen, besser zu verstehen. Wie bereits viele eindrucksvolle Beispiele der letzten Jahre belegen, dient sie letztendlich auch dazu, völlig neue therapeutische Konzepte zu entwickeln, die eine erfolgreiche individuelle und gleichzeitig nebenwirkungsfreiere Behandlung dieser Patienten ermöglichen.
Genotyping of the LCT (T/C-13910) polymorphism on the LightCycler using fluorescent hybridisation probes Genotypisierung des LCT (T/C-13910)-Polymorphismus am LightCycler mittels fluoreszenzmarkierter Hybridisierungssonden
Authors: Stolba Robert , Rezanka Erwin , Eckhard Ulrich , Wider Günter
Published: August 2005

Primary adult-type hypolactasia is a hereditary metabolic condition which leads to clinical manifestation usually during early adulthood and is frequently associated with clinical symptoms of lactose intolerance. The prevalence of adult-type hypolactasia varies extremely in different populations; in Central Europe, it is about 15–40%. The CC homozygous genotype of the LCT (T/C-13910) polymorphism on chromosome 2q21 is strongly associated with primary adult-type hypolactasia. For rapid genotyping by real-time PCR we developed a genetic test using fluorescently labeled hybridization probes. We genotyped 60 patients with clinically suspected lactose intolerance and compared the results of the new genetic test with clinical data and lactose H2 breath test results, the clinically most widely used non-invasive test for the diagnosis of lactose malabsorption. 80% of the CC individuals were lactose malabsorbers, whereas only 30% of the TC or TT individuals were classified as lactose malabsorbers according to their H2 breath test results. The genetic test ist suitable for routine clinical applications and of great value for the reliable differentiation between lactose malabsorbers with adult-type hypolactasia and patients with secondary hypolactasia due to different gastrointestinal disorders or small intestinal bacterial overgrowth.
Entwicklung der Klinischen Chemie und Laboratoriumsmedizin in Deutschland History of Clinical Chemistry and Laboratory Medicine in Germany
Authors: Kruse-Jarres Jürgen D.
Published: August 2005

Die Klinische Chemie und Laboratoriumsmedizin, die beiden Wurzeln eines einheitlichen Faches, demonstrieren innerhalb der medizinischen Disziplinen am besten, wie bahnbrechende Erkenntnisse aus der biochemischen, biologischen, chemisch-analytischen, technischen und informationstechnologischen Grundlagenforschung zum Nutzen einer besseren Diagnostik und Therapiekontrolle in die medizinische Praxis transferiert werden. Dies hat die ereignisreiche Geschichte dieses Faches vor allem in den vergangenen 150 Jahren zeigen können. Die Entwicklung der Klinischen Chemie und Laboratoriumsmedizin in Deutschland wird aufgezeichnet und ihre Rolle als ein wichtiger Berührungs- und Drehpunkt zwischen zwischen Naturwissenschaften und Medizin dargestellt.
Retinoic Acid Signaling Identifies a Distinct Precursor Population in the Developing and Adult Forebrain
Authors: Haskell Gloria Thompson , LaMantia Anthony-Samuel
Published: August 2005

We asked whether retinoic acid (RA), an established transcriptional regulator in regenerating and developing tissues, acts directly on distinct cell classes in the mature or embryonic forebrain. We identified a subset of slowly dividing precursors in the adult subventricular zone (SVZ) that is transcriptionally activated by RA. Most of these cells express glial fibrillary acidic protein, a smaller subset expresses the epidermal growth factor receptor, a few are terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling positive, and they can be mitotically labeled by sustained rather than acute bromodeoxyuridine exposure. RA activation in similar cells in SVZ-derived neurospheres depends on retinoid synthesis from the premetabolite retinol. The apparent influence of RA on precursorsin vitrois consistent with key properties of RA activation in the SVZ; in neurospheres, altered retinoid signaling elicits neither cell death nor an acute increase in cell proliferation. There is apparent continuity of RA signaling in the forebrain throughout life. RA-activated, proliferative precursors with radial glial characteristics are found in the dorsal lateral ganglionic eminence and ventrolateral palliumembryonic rudiments of the SVZ. Thus, endogenous RA signaling distinguishes subsets of neural precursors with glial characteristics in a consistent region of the adult and developing forebrain.