bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathophysiologie und Therapie der AMD: Therapeutischer Anti‐VEGF‐Einsatz in der Augenheilkunde
Authors: Finger Robert P. , Fleckenstein Monika , Scholl Hendrik P.N. , Holz Frank G. 
Published: October 2007

AbstractDie altersabhängige Makuladegeneration (AMD) ist in allen Industrienationen die häufigste Erblindungsursache. Allein in Deutschland sind ca. 4,5 Millionen Menschen betroffen. Angesichts der demographischen Entwicklung wird die Anzahl der Betroffenen weiter zunehmen. Die Spätstadien der Erkrankung gehen unter anderem mit einem Verlust der zentralen Sehschärfe und damit der Lesefähigkeit sowie häufig der selbstständigen Lebensführung einher. Umso dringlicher ist die Entwicklung neuer wirksamer Therapieverfahren, mit denen der Verlust des zentralen Sehens verhindert werden kann. Basierend auf neuen Erkenntnissen zur Pathogenese konnte die Antiangiogenese als neue Therapieform der neovaskulären AMD etabliert werden. Mittels wiederholter intravitrealer Injektion antiangiogen wirksamer Präparate können Wachstum und Permeabilität neovaskulärer Membranen bei der AMD günstig beeinflusst werden. Erste Ergebnisse aus Zulassungsstudien und aus der klinischen Praxis sind sehr viel versprechend. Es bleibt abzuwarten, ob die Langzeitergebnisse nach jahre‐ und jahrzehntelanger Therapie und die langfristigen unerwünschten Wirkungen ebenfalls so positiv ausfallen werden.
Ranibizumab bei Makuladegeneration. Angiogenese‐Hemmung gegen Sehverlust
Authors: Mohr‐Andrä Marion , Mohr Klaus 
Published: October 2007

AbstractMit Ranibizumab, einem humanisierten Antikörperfragment gegen den vaskulären endothelialen Wachstumsfaktor A (VEGF‐A) steht nun zum ersten Mal ein Arzneimittel zur Verfügung, das den Verlust des Sehvermögens bei der feuchten Form der altersabhängigen Makuladegeneration (AMD) nicht nur aufhalten, sondern zum Teil auch rückgängig machen kann. Allerdings ist die Therapie sehr aufwändig (monatliche Injektion direkt in den Glaskörper des Auges unter aseptischen OP‐Bedingungen) und teuer (reine Arzneimittelkosten: ca. 1500 R/Monat).Unerwünschte Arzneimittelwirkungen traten in den Zulassungsstudien für Ranibizumab selten auf, und standen meist im Zusammenhang mit der Applikationsmethode (Entzündungen des Auges).Bevacizumab, ein anderer Inhibitor des VEGF‐A, der zur Therapie des Kolon‐ und Rektumkarzinoms zugelassen ist, wird in den USA im Off‐label‐use als kostengünstigere Alternative verwendet. Vergleichende Studien zur Wirksamkeit und Verträglichkeit von Bevacizumab bei der Indikation AMD fehlen gegenwärtig, sollen aber im Laufe dieses Jahres begonnen werden.
Die neue Karriere des Thalidomids. Ein altes Schlafmittel als Cancerostatikum
Authors: Holzgrabe Ulrike 
Published: October 2007

AbstractZusammenfassend kann festgestellt werden, dass Lenalidomid, das strukturell seiner Muttersubstanz Thalidomid sehr ähnlich ist, wesentlich effektiver in der Behandlung des MM und MDS ist als Thalidomid. Außerdem ist das Nebenwirkungsspektrum und auch die Nebenwirkungshäufigkeit günstiger. Hauptnebenwirkung von Lenalidomid ist die Veränderung des Blutbildes, insbesondere die Erniedrigung der weißen Blutkörperchen und der Blutplättchen. Viele Studien zu beiden Substanzen befinden sich in frühen Stadien, sodass eine abschließende Beurteilung noch aussteht. Lenalidomid wird zurzeit auch in Kombination mit anderen Chemotherapeutika für die Behandlung solider Tumore getestet.
Aspergillus fumigatus und Angiogenese. Von einer Zufallsentdeckung zum Rationalen Drug‐Design
Authors: Klein Christian 
Published: October 2007

AbstractDer Schimmelpilz Aspergillus fumigatus produziert einen potenten Angiogenesehemmstoff, das Fumagillin. Diese Substanz war einer der ersten niedermolekularen Angiogeneseinhibitoren und trug wesentlich dazu bei, diese therapeutische Strategie überhaupt erst interessant zu machen.
Angiogenese‐Inhibitoren der Zukunft. Getreu dem Motto: Von der Versorgung abschnüren!
Authors: Zündorf Ilse , Dingermann Theo 
Published: October 2007

AbstractMit dem Wissen um die bei der Angiogenese beteiligten Regulatormoleküle, die sich grob in die drei Gruppen der zirkulierenden Zytokine und Wachstumsfaktoren, der Komponenten der extrazellulären Matrix und der membrangebundenen Proteine einteilen lassen, explodierte quasi die Zahl der möglichen Angiogenese‐Inhibitoren. Das Hauptaugenmerk liegt auf der VEGF‐vermittelten Signalkaskade, die an unterschiedlichsten Stellen inhibiert wird. Die meisten Wirkstoffe in der Entwicklung adressieren die Tyrosinkinase‐Aktivität des VEGF‐Rezeptors. Primäres Einsatzgebiet derartiger Wirkstoffe ist die Tumortherapie. Ganz nebenbei können sich daraus allerdings auch weitere Therapieoptionen für die feuchte Macula‐Degeneration ergeben. Es bleibt allerdings abzuwarten, wie viele der Substanzen in klinischer Testung es wirklich bis zur Marktreife schaffen.
Pharmakoökonomie: Fluch oder Segen für die medizinische Versorgung? Überlegungen nicht nur zu Angiogenese‐Hemmern
Authors: Schöffski Oliver , Cremers Yvonne 
Published: October 2007

AbstractInnovative neue Arzneimittel wie die Angiogenesehemmer verursachen im Gesundheitssystem hohe Kosten. In diesem Beitrag soll dargestellt werden, wie sich die Gesundheitsökonomie diesem Thema nähert, wie sie versucht Kennzahlen zu ermitteln, durch die eine effiziente Steuerung des Gesundheitswesens möglich wird. Es ist aber nicht zu beschönigen: Es geht im Endeffekt um Rationierung und damit um ein unangenehmes Thema.
Lactivicin – ein Antibiotikum gegen Penicillin‐resistente Pneumokokken
Authors: Holzgrabe Ulrike 
Published: October 2007

Abstractβ‐Lactam‐Antibiotika wie die Penicilline und Cephalosporine entfalten ihre bakteriostatische Wirkung durch die Hemmung der so genannten Penicillin‐bindenden Proteine (kurz PBPs genannt), die für die Synthese der Bakterienzellwand verantwortlich sind. Eben diese PBPs werden bei der Resistenzentstehung von den Bakterien mutiert, so dass die β‐Lactam‐Antibiotika nur noch eine kleine Affinität zu den PBPs haben.
Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth
Authors: Flood Veronica H. , Galderisi Faith C. , Lowas Stefanie R. , Kendrick Angela , Boshkov Lynn K. 
Published: October 2007

AbstractLate hemorrhagic disease of the newborn (HDN) presents 0.5–6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN. Pediatr Blood Cancer 2008;50:1075–1077. © 2007 Wiley‐Liss, Inc.
Hospitalization rates of generic metoprolol compared with the original beta‐blocker in an epidemiological database study
Authors: Ahrens Wolfgang , Hagemeier Constantin , Mühlbauer Bernd , Pigeot Iris , Püntmann Isabel , Reineke Achim , Steinbach Monica , Timm Jürgen 
Published: October 2007

AbstractPurposeA less favourable galenic profile of generic formulations of the beta‐blocker metoprolol raised the concern of a higher risk for serious cardiovascular (CV) events. We assessed hospital admission rates for CV diseases and prescription prevalences of various drugs using claims data of statutory health insurances (SHIs) to compare the incidence of serious CV events among users of original and generic metoprolol. Index events included hospitalization due to myocardial infarction, hypertensive crisis and stroke.MethodsData files of three SHIs were linked with dispensing data of drug prescriptions from each pharmacy's electronic data processing centre on an individual basis. Incidences of hospital admissions among patients receiving original metoprolol and among patients treated with the generic equivalent were compared by logistic regression, stratified for Bremen and the rest of Northern Germany. Risk estimates and confidence intervals were adjusted for confounders.ResultsA total of 49 673 patients receiving metoprolol were identified within a cohort of 3 649 285 insurance members. While the crude analysis revealed a higher risk for index events in patients receiving the generic drug (Bremen: RR 1.45; Northern Germany: RR 1.14), no elevated risk remained after confounder adjustment (Bremen: OR 1.06; Northern Germany: OR 1.04). Among co‐morbid conditions considered as confounders, a previous CV event and an elevated thromboembolic risk exerted the strongest effect on index events.ConclusionsSHI data are a valuable source for pharmacoepidemiology and health services research in Germany. Incidence rates of serious CV events did not reveal any noticeable differences between the original and the generic group after confounder adjustment. Copyright © 2007 John Wiley & Sons, Ltd.
Is mechanical pain threshold after transcutaneous electrical nerve stimulation (TENS) increased locally and unilaterally? A randomized placebo‐controlled trial in healthy subjects
Authors: Aarskog Reidar , Johnson Mark I. , Demmink Jan Hendrik , Lofthus Anne , Iversen Vegard , Lopes‐Martins Rodrigo , Joensen Jon , Bjordal Jan M. 
Published: October 2007

AbstractBackground and Purpose. It is not fully understood how transcutaneous electrical nerve stimulation (TENS) intensity affects mechanical pain threshold. Method. Sixty‐six healthy volunteers (13 male, 53 female; 132 hands) without prior experience of TENS participated in the study, which comprised a randomized single‐blind controlled trial. TENS was administered for 20 minutes through electrodes (25 × 25 mm) placed on the hands and forearms with a fixed frequency of 100 Hz and pulse duration of 150 µs. TENS intensity was randomized and allocated in a concealed manner so that one arm received TENS with stimulation intensity set at participants' subjective sensory threshold and the other received TENS with stimulation intensity continuously adjusted by physiotherapists to a strong but comfortable non‐painful stimulation. Observers were blinded to stimulation intensity levels. Results. Mechanical pain threshold increased significantly, by a mean total of 0.79 kg/cm2 (95% confidence interval [95% CI]: 0.54–1.04) (p < 0.001) on the strong but comfortable non‐painful stimulation side. The mean change in mechanical pain threshold on the sensory threshold side was 0.19 kg/cm2 and did not reach statistical significance (95% CI–0.15 to 0.51). The mean stimulation intensity level for sensory threshold was 6.7 mA (95% CI: 5.65 to 7.83) which was significantly lower (p < 0.001) than the mean stimulation intensity for the strong stimulation, which was 20.5 mA (95% CI 16.6 to 24.4), respectively. The strong stimulation levels were, on average, 3.05 times higher than sensory threshold, but individual variations were large (range 1.2–6.1). Conclusions. TENS administered at a strong but comfortable non‐painful stimulation intensity increases mechanical pain threshold ipsi‐laterally in healthy subjects, whereas TENS administered at sensory threshold intensity does not. TENS may be ineffective if electrodes are placed contralaterally or distant to the pain site and if stimulation intensity levels are not titrated to subjective strong levels. Further clinical trials are needed to clarify if these findings may also be generalized to populations of chronic pain sufferers. Copyright © 2007 John Wiley & Sons, Ltd.
Free‐energy landscape of kinesin by a realistic lattice model
Authors: Kenzaki Hiroo , Kikuchi Macoto 
Published: October 2007

AbstractStructural fluctuations in the thermal equilibrium of the kinesin motor domain are studied using a lattice protein model with Gō interactions. By means of the multi‐self‐overlap ensemble Monte Carlo method and the principal component analysis, the free‐energy landscape is obtained. It is shown that kinesins have two subdomains that exhibit partial folding/unfolding at functionally important regions: one is located around the nucleotide binding site and the other includes the main microtubule binding site. These subdomains are consistent with structural variability that was reported recently based on experimentally‐obtained structures. On the other hand, such large structural fluctuations have not been captured by B‐factor or normal mode analyses. Thus, they are beyond the elastic regime, and it is essential to take into account chain connectivity for studying the function of kinesins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Kinetic and structural properties of triosephosphate isomerase from Helicobacter pylori
Authors: Chu Chen‐Hsi , Lai Yi‐Ju , Huang Haimei , Sun Yuh‐Ju 
Published: October 2007

AbstractTriosephosphate isomerase (TIM) catalyzes the interconversion between dihydroxyacetone phosphate and D‐glyceraldehyde‐3‐phosphate in the glycolysis–gluconeogenesis metabolism pathway. The Helicobacter pylori TIM gene (HpTIM) was cloned, and HpTIM was expressed and purified. The enzymatic activity of HpTIM for the substrate GAP was determined (Km = 3.46 ± 0.23 mM and kcat = 8.8 × 104 min−1). The crystal structure of HpTIM was determined by molecular replacement at 2.3 Å resolution. The overall structure of HpTIM was (β/α)β(β/α)6, which resembles the common TIM barrel fold, (β/α)8; however, a helix is missing after the second β‐strand. The conformation of loop 6 and binding of phosphate ion suggest that the determined structure of HpTIM was in the “closed” state. A highly conserved Arg‐Asp salt bridge in the “DX(D/N)G” motif of most TIMs is absent in HpTIM because the sequence of this motif is “211SVDG214.” To determine the significance of this salt bridge to HpTIM, four mutants, including K183S, K183A, D213Q, and D213A, were constructed and characterized. The results suggest that this conserved salt bridge is not essential for the enzymatic activity of HpTIM; however, it might contribute to the conformational stability of HpTIM. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The geometry of α‐sheet: Implications for its possible function as amyloid precursor in proteins
Authors: Hayward Steven , Milner‐White E. James 
Published: October 2007

Abstractα‐sheet has been proposed as the main constituent of the prefibrillar intermediate during amyloid formation. Here the helical parameters of the α‐sheet strand are calculated from average main‐chain dihedral angles reported from molecular dynamics simulations. It is an almost linear polypeptide that forms a right‐handed helix of about 100 Å diameter, with 100 residues and a rise of 30 Å per turn. The strands are curved but untwisted, which implies that neighboring strands need not coil to make interstrand hydrogen bonds. This suggests that compared to β‐sheets in native folded proteins, α‐sheets can be larger and stack more easily to create extensive 3D blocks. It is shown that α‐sheet is related to a category of structures termed “mirror” structures. Mirror structures have repetitive pairs of main‐chain dihedral angles at residues i and i+1 that satisfy the condition ϕi+1 = −ψi, ψi+1 = −ϕi. They are uniquely identified by the two orientations of their peptide planes, specified by ϕi and ψi. Their side chains point alternately in opposite directions. Interestingly, their conformations are insensitive to ϕi and ψi in that the pseudo dihedral angle formed by four consecutive Cα atoms is always close to 180°. There are two types: “β‐mirror” and “α‐mirror” structure; β‐mirror structures relate to β‐sheet by small peptide plane rotations, of less than 90°, while α‐mirror structures are close to α‐sheet and relate to β‐sheet by ∼180° peptide plane flips. Most mirror structures, and in particular the α‐mirror, form wide helices with diameters 50–70 Å. Their gentle curvature, and therefore that of the α‐sheet, arises from the orientation of successive peptide units causing the difference in the bond angles at the C and N atoms of the peptide unit to gradually change the direction of the chain. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Contact rearrangements form coupled networks from local motions in allosteric proteins
Authors: Daily Michael D. , Upadhyaya Tarak J. , Gray Jeffrey J. 
Published: October 2007

AbstractAllosteric proteins bind an effector molecule at one site resulting in a functional change at a second site. We hypothesize that networks of contacts altered, formed, or broken are a significant contributor to allosteric communication in proteins. In this work, we identify which interactions change significantly between the residue–residue contact networks of two allosteric structures, and then organize these changes into graphs. We perform the analysis on 15 pairs of allosteric structures with effector and substrate each present in at least one of the two structures. Most proteins exhibit large, dense regions of contact rearrangement, and the graphs form connected paths between allosteric effector and substrate sites in five of these proteins. In the remaining 10 proteins, large‐scale conformational changes such as rigid‐body motions are likely required in addition to contact rearrangement networks to account for substrate–effector communication. On average, clusters which contain at least one substrate or effector molecule comprise 20% of the protein. These allosteric graphs are small worlds; that is, they typically have mean shortest path lengths comparable to those of corresponding random graphs and average clustering coefficients enhanced relative to those of random graphs. The networks capture 60–80% of known allostery‐perturbing mutants in three proteins, and the metrics degree and closeness are statistically good discriminators of mutant residues from nonmutant residues within the networks in two of these three proteins. For two proteins, coevolving clusters of residues which have been hypothesized to be allosterically important differ from the regions with the most contact rearrangement. Residues and contacts which modulate normal mode fluctuations also often participate in the contact rearrangement networks. In summary, residue–residue contact rearrangement networks provide useful representations of the portions of allosteric pathways resulting from coupled local motions. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Simultaneous determination of new thioamphetamine designer drugs in plasma by capillary electrophoresis coupled with mass spectrometry
Authors: Boatto Gianpiero , Nieddu Maria , Pirisi Maria Antonietta , Dessì Giuseppina 
Published: October 2007

AbstractA simple method for the simultaneous identification and quantification of four 2,5‐methylenedioxy derivatives of 4‐thioamphetamine (ALEPH series) in plasma samples was developed. The method consists of solid‐phase extraction (SPE) using a Bond Elut C18 cartridge and capillary electrophoresis coupled with electrospray ionisation mass spectrometry (CE/ESI‐MS). The SPE method used required only simple steps and provided a clean extract from which identification of each drug was feasible, even at low concentrations. The method was validated according to international guidelines. The calibration curves were linear over the concentration range of 50 to 1000 ng/mL for all drugs with correlation coefficients that exceeded 0.998. The lower limits of detection of the drugs were 23–43 ng/mL. The absolute recoveries for the drugs were 64–92% and 75–96% at concentrations of 100 and 500 ng/mL, respectively. The validation data (precision, accuracy, and recovery) show the reproducibility and selectivity of the method. This clean and simple method allows the routine detection of designer drugs such as thioamphetamines which may become a serious problem in the control of illegal drugs. Copyright © 2007 John Wiley & Sons, Ltd.
Extended Algorithm for Simulation of Light Transport in Single Crystal Scintillation Detectors for S(T)EM
Authors: Schauer Petr 
Published: October 2007

AbstractThe new extended Monte Carlo (MC) simulation method for photon transport in S(T)EM back scattered electron (BSE) scintillation detection systems of various shapes is presented in this paper. The method makes use of the random generation of photon emission from a scintillator luminescent centre and describes the trajectory of photons and the efficiency of their transport toward the photocathode of the photomultiplier tube. The paper explains a new algorithm for determining the position of interaction of the photon with the surface of the single crystal scintillator or of the light guide with nearly arbitrary shapes. Some examples of the utilization of the simulation method are also included, and conclusions for very simple edge‐guided signal (EGS) scintillation detection systems made. The computer optimized design of the BSE scintillation detector for the S 4000 Hitachi SEM was chosen to demonstrate the capability of this MC simulation method. SCANNING 29: 249–253, 2007. © 2007 Wiley Periodicals, Inc.
Structural BIM: discussion, case studies and latest developments
Authors: Robinson Clive 
Published: October 2007

AbstractThis paper discusses the current state of building information modelling (BIM) from the structural point of view, incorporating the migration from 2D to 3D solutions. Open interfaces are also considered and how they provide access to BIM information away from the specialist modelling solutions to more conventional software tools, allowing closer design team collaboration. Two case studies are also highlighted to identify the benefits obtained from the structural BIM solution. Copyright © 2007 John Wiley & Sons, Ltd.
Kettles of fish: or, does unilateral idiomaticity exist?
Authors: Prodromou Luke 
Published: October 2007

ABSTRACTSome reflections on the nature of ELF. The focus in this article is what scholars of English as a Lingua Franca (ELF) have referred to as ‘unilateral idiomaticity’ (UI): the use by speakers and writers of idiomatic language which is not understood by the other participants in the interaction. The writer will attempt to identify actual occurrences of UI, drawing on both corpus evidence and an email survey of fifty L1 and L2 ELF-users and will also draw some implications for what we mean by ‘competence’ in lingua franca contexts.
Catchwords as markers of change in China
Authors: Hou Jinxiang 
Published: October 2007

ABSTRACTA CATCHWORD is a lexical item or phrase, whether created within a particular language or adopted from foreign languages through translation or transliteration or a combination of the two. In Chinese discourse, catchwords spread rapidly within a particular group of people at a particular time and in a particular context (cf. Gu Wei, 2004): a definition from work undertaken at the Institute of Applied Linguistics (founded in 2002 at the Beijing Language and Culture University). The topic is the subject of a treatise, ‘The longitudinal study of catchwords in newspapers’ and is one of the items on the agenda of the Tenth Five-Year Plan, for consideration by the Chinese Language and Characters Committee. Zhang Pu (2003), a professor of language information processing at Beijing Language and Culture University has argued that ‘[a] catchword is not only a lexical phenomenon, but also indicates people's values from a cultural psychology point of view, as well as reflecting social reality’.
An endless coded stream
Authors: Martin Assunta 
Published: October 2007

ABSTRACTA brief look at the debate between sociolinguists and linguists with some examples of euphemisms that have surfaced into common usage offers revealing insights reflecting contemporary social perceptions. Sociolinguists who investigate the role and function of language are not so much concerned with the way language utterances are generated and constructed as with the ways that language is used in society as a means to communicate. Traditionally, linguists steered clear of the murky waters of social relevance and social context in use, believing that it is a study that cannot yield predictions of future usage, be measured objectively, or tested for accuracy.