bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Molecular Basis for A‐Site Mutations Conferring Aminoglycoside Resistance: Relationship between Ribosomal Susceptibility and X‐ray Crystal Structures
Authors: Pfister Peter , Hobbie Sven , Vicens Quentin , Böttger Erik C. , Westhof Eric 
Published: September 2003

AbstractAminoglycoside antibiotics target the 16S ribosomal RNA (rRNA) bacterial A site and induce misreading of the genetic code. Point mutations of the ribosomal A site may confer resistance to aminoglycoside antibiotics. The influence of bacterial mutations (introduced by site‐directed mutagenesis) on ribosomal drug susceptibility was investigated in vivo by determination of minimal inhibitory concentrations. To determine the origin of the various resistance phenotypes at a molecular level, the in vivo results were compared with the previously published crystal structures of paromomycin, tobramycin, and geneticin bound to oligonucleotides containing the minimal A site. Two regions appear crucial for binding in the A site: the single adenine residue at position 1408 and the non‐Watson–Crick U1406⋅U1495 pair. The effects of mutations at those positions are modulated by the nature of the substituent at position 6′ (either hydroxy or ammonium group) on ring I, by the number of positive charges on the antibiotic, and by the linkage between rings I and III (either 4,5 or 4,6). In particular, the analysis demonstrates: 1) that the C1409–G1491 to A1409–U1491 polymorphism (observed in 15 % of bacteria) is not associated with resistance, which indicates that it does not affect the stacking of ring I on residue 1491, 2) that the high‐level resistance to 6′‐NH${_{3}^{+}}$ aminoglycosides exhibited by the A1408G mutation most probably results from the inability of ring I forming a pseudo base pair with G1408, which prevents its insertion inside the A site helix, and 3) that mutations of the uracil residues forming the U1406⋅U1495 pair either to cytosine or to adenine residues mostly confer low to moderate levels of drug resistance, whereas the U1406C/U1495A double mutation confers high‐level resistance (except for neomycin), which suggests that aminoglycoside binding to the wild‐type A site and its functional consequences strongly depend on a particular geometry of the U1406⋅U1495 pair. The relationships between the resistance phenotypes observed in vivo and the interactions described at the molecular level define the biological importance of the different structural interactions observed by X‐ray crystallography studies.
Evaluation of Bacterial RNase P RNA as a Drug Target
Authors: Willkomm Dagmar K. , Gruegelsiepe Heike , Goudinakis Olga , Kretschmer‐Kazemi Far Rosel , Bald Rolf , Erdmann Volker A. , Hartmann Roland K. 
Published: September 2003

AbstractRNA has gained increasing importance as a therapeutic target. However, so far mRNAs rather than stable cellular RNAs have been considered in such studies. In bacteria, the tRNA‐processing enzyme RNase P has a catalytic RNA subunit. Fundamental differences in structure and function between bacterial and eukaryotic RNase P, and its indispensability for cell viability make the bacterial enzyme an attractive drug target candidate. Herein we describe two approaches utilized to evaluate whether the catalytic RNA subunit of bacterial RNase P is amenable to inactivation by antisense‐based strategies. In the first approach, we rationally designed RNA hairpin oligonucleotides targeted at the tRNA 3′‐CCA binding site (P15 loop region) of bacterial RNase P RNA by attempting to include principles derived from the natural CopA–CopT antisense system. Substantial inactivation of RNase P RNA was observed for Type A RNase P RNA (such as that in Escherichia coli) but not for Type B (as in Mycoplasma hyopneumoniae). Moreover, only an RNA oligonucleotide (Eco 3′) complementary to the CCA binding site and its 3′ flanking sequences was shown to be an efficient inhibitor. Mutation of Eco 3′ and analysis of other natural RNase P RNAs with sequence deviations in the P15 loop region showed that inhibition is due to interaction of Eco 3′ with this region and occurs in a highly sequence‐specific manner. A DNA version of Eco 3′ was a less potent inhibitor. The potential of Eco 3′ to form an initial kissing complex with the P15 loop did not prove advantageous. In a second approach, we tested a set of oligonucleotides against E. coli RNase P RNA which were designed by algorithms developed for the selection of suitable mRNA targets. This approach identified the P10/11‐J11/12 region of bacterial RNase P RNA as another accessible region. In conclusion, both the P15 loop and P10/11‐J11/12 regions of Type A RNase P RNAs seem to be promising antisense target sites since they are easily accessible and sufficiently interspersed with nonhelical sequence elements, and oligonucleotide binding directly interferes with substrate docking to these two regions.
Stereoselective Synthesis using Immobilized Diels–Alderase Ribozymes
Authors: Schlatterer Jörg C. , Stuhlmann Friedrich , Jäschke Andres 
Published: September 2003

AbstractDevelopment of artificial ribozymes by in vitro selection has so far, mostly been addressed from the viewpoint of fundamental research. However, such ribozymes also have high potential as selective catalysts in practical syntheses. Immobilization of an active and selective ribozyme is an important step towards this end. A 49‐nucleotide RNA molecule that was previously found to stereoselectively catalyze Diels–Alder reactions between various anthracene dienes and maleimide dienophiles was quantitatively immobilized on an agarose matrix by periodate oxidation of the 3′‐terminal ribose and coupling to a hydrazide moiety. Typical loadings were 45 pmol μL−1 gel. The specific activity was comparable to that of soluble ribozyme, and high enantioselectivities were obtained in catalyzed cycloadditions. The catalytic matrix was found to be stable and could be regenerated about 40 times with only minimal reduction of catalytic activity. Like the soluble ribozyme, the immobilized catalyst stereoselectively converts various diene and dienophile substrates. By using either natural D‐RNA or enantiomeric L‐RNA, both product enantiomers were made synthetically accessible with similar selectivities.
NMR Spectroscopy of RNA
Authors: Fürtig Boris , Richter Christian , Wöhnert Jens , Schwalbe Harald 
Published: September 2003

AbstractNMR spectroscopy is a powerful tool for studying proteins and nucleic acids in solution. This is illustrated by the fact that nearly half of all current RNA structures were determined by using NMR techniques. Information about the structure, dynamics, and interactions with other RNA molecules, proteins, ions, and small ligands can be obtained for RNA molecules up to 100 nucleotides. This review provides insight into the resonance assignment methods that are the first and crucial step of all NMR studies, into the determination of base‐pair geometry, into the examination of local and global RNA conformation, and into the detection of interaction sites of RNA. Examples of NMR investigations of RNA are given by using several different RNA molecules to illustrate the information content obtainable by NMR spectroscopy and the applicability of NMR techniques to a wide range of biologically interesting RNA molecules.
Oligonucleotide‐Based Knockdown Technologies: Antisense Versus RNA Interference
Authors: Achenbach Tatjana V. , Brunner Bodo , Heermeier Kathrin 
Published: September 2003

AbstractThe postgenomic era is characterized by an almost intimidating amount of information regarding the sequences and expression of previously unknown genes. In response, researchers have developed an increasing interest in functional studies. At the start of such a study, one may have little more than sequence information and bioinformatic annotation. The next step is to hypothesize a potential role in the context of a cell. Testing of the hypothesis needs to be fast, cheap, and applicable to a large number of genes. Knockdown methods that rely on binding of antisense oligonucleotides to mRNA combined with a subsequent functional assay in cell culture fulfil these requirements: sequence information is sufficient for synthesis of active inhibitors. Depending on the in vitro model chosen, knockdown of gene expression can be achieved with medium or even high throughput. The two most popular methods of knockdown in cell culture are the use of antisense oligonucleotides that rely on ribonuclease H (RNAse H)‐dependent cleavage of mRNA, and RNA interference triggered by small double‐stranded RNA molecules. Both methods act in a sequence‐specific manner and can give efficient knockdown. In both cases, researchers struggle with nonspecific “off‐target” effects and the difficulty of site selection. Studies that compare the methods differ in their judgment as to which method is superior.
Cover Picture: Targeting RNA with Small Molecules (ChemBioChem 10/2003)
Authors: Tor Yitzhak 
Published: September 2003

AbstractThe cover picture shows the processes involved in the search for small molecules as potent and selective RNA binders. Motivation comes from the desire to control cell function at the RNA level and to identify novel approaches to specifically combat pathogens by targeting their unique RNA sequences or RNA–protein complexes. Inspiration comes from nature; in particular, from aminoglycosides, a family of naturally occurring antibiotics that has been shown to target the bacterial ribosome. The discovery process involves identifying RNA targets (schematically shown as a ribosome or a virus), devising unique assays (e.g. a solid‐phase assay), and generating the necessary knowledge and lead structures through design, synthesis, and systematic evaluation of biological activity. Further details can be found in the article by Y. Tor on p. 998 ff.
Elective coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy
Authors: Jessup David B. , Coletti Andrew T. , Muhlestein Joseph B. , Barry William H. , Shean Frederic C. , Whisenant Brian K. 
Published: September 2003

AbstractThe management of patients anticoagulated with warfarin and referred for coronary angiography presents a substantial challenge to the physician who must minimize risks of periprocedural hemorrhage and thromboembolism. The aim of this study was to evaluate the feasibility and safety of performing diagnostic coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Patients treated with warfarin were prospectively identified and enrolled in the study. Nineteen diagnostic cardiac catheterizations and six percutaneous coronary interventions were performed in 23 patients. The mean international normalized ratio was 2.4 ± 0.5 (range, 1.8–3.5). Hemostasis was achieved with AngioSeal following 21 procedures and with Perclose following 4 procedures. No patient experienced a predefined endpoint. Specifically, no patient experienced procedure‐related myocardial infarction, major or minor bleeding. We conclude that cardiac catheterization and percutaneous coronary intervention may be considered in the setting of uninterrupted warfarin therapy. Catheter Cardiovasc Interv 2003;60:180–184. © 2003 Wiley‐Liss, Inc.
Catheter‐based 32P β‐radiation after stent implantation in porcine coronary arteries: Role of source‐centering and geographical miss
Authors: Maeng Michael , Busk Martin , Tanderup Kari , Mertz Henrik , Andersen Henning Rud , Thuesen Leif 
Published: September 2003

AbstractThe present study examined the role of source‐centering and geographical miss in vascular brachytherapy. After implantation of 13 mm long stents, 38 coronary arteries in 13 pigs were randomly assigned to centered brachytherapy (n = 13), eccentric brachytherapy (n = 13), or no radiation (n = 12). Geographical miss was avoided by careful placement of a 27 mm 32P β‐radiation source. Restenosis was quantified by angiography, histomorphometry, and intravascular ultrasound at 28 days. Source‐centering led to a significant (P < 0.001) reduction of in‐stent area stenosis (centered radiation, 12% ± 5%; eccentric radiation, 37% ± 21%; control arteries, 41% ± 13%). Despite 7 mm coverage of the edge segments, radiation was found to induce edge stenosis due to neointima formation and constrictive vascular remodeling. We conclude that centered radiation was superior to eccentric radiation in reducing in‐stent luminal narrowing while radiation‐induced edge stenosis was still observed despite extension of the radiation zone to 7 mm beyond the stent edges. Catheter Cardiovasc Interv 2003;60:247–257. © 2003 Wiley–Liss, Inc.
Combined distal embolization protection and rheolytic thrombectomy to facilitate percutaneous revascularization of totally occluded saphenous vein grafts
Authors: Gaitonde Rajdeep S. , Sharma Naveen , von der Lohe Elisabeth , Kalaria Vijay G. 
Published: September 2003

AbstractTotally occluded saphenous vein grafts are difficult to treat percutaneously with a higher likelihood of distal embolization and slow‐flow or no‐reflow during percutaneous interventions. The PercuSurge system, which utilizes a distal balloon occlusive device, has been shown to improve clinical outcomes during saphenous vein graft (SVG) interventions. This device may not be optimal in the setting of heavy thrombus or debris burden, a situation frequently encountered in totally occluded SVGs. Rheolytic thrombectomy facilitates percutaneous interventions by effectively removing intraluminal thrombus and debris but lacks distal embolization protection. We report our experience with the synergistic use of balloon‐based distal embolization protection (PercuSurge) and rheolytic thrombectomy (AngioJet) to optimize percutaneous revascularization of totally occluded SVGs. Catheter Cardiovasc Interv 2003;60:212–217. © 2003 Wiley‐Liss, Inc.
Transcatheter closure of a ruptured ventricular septum following inferior myocardial infarction and cardiogenic shock
Authors: Schiele Thomas M. , Kozlik‐Feldmann Rainer , Sohn Hae‐Young , Stempfle Hans‐Ulrich , Küchle Claudius , Schopohl Jochen , Theisen Karl , Leibig Marcus , Klauss Volker 
Published: September 2003

AbstractElective transcatheter closure of congenital septal defects has emerged as a valuable method, but the clinical experience on occlusion of ventricular septal rupture after myocardial infarction is very limited. We report a case of fatal outcome in a patient with inferior myocardial infarction and cardiogenic shock despite technically successful transcatheter closure of a large complex ventricular septal defect. Catheter Cardiovasc Interv 2003;60:224–228. © 2003 Wiley‐Liss, Inc.
Transcatheter closure of a coronary sinus defect with an Amplatzer septal occluder
Authors: Di Bernardo Stefano , Fasnacht Margrit , Berger Felix 
Published: September 2003

AbstractWe report a successful transcatheter closure of a coronary sinus defect using an Amplatzer septal occluder in a 9.5‐year‐old boy suffering from a significant volume overload due to left‐to‐right shunt. Catheter Cardiovasc Interv 2003;60:287‐290
Endocardial cryotherapy as a novel strategy of improving myocardial perfusion in a patient with severe coronary artery disease
Authors: Segev Amit , Strauss Bradley H. , Coates Geoffry , Freeman Michael R. , Gallo Richard 
Published: September 2003

AbstractPatients with intractable angina pectoris due to end‐stage coronary artery disease who are not amenable to conventional revascularization provide a therapeutic challenge. We describe the first published case of a young patient with intractable coronary artery disease that was successfully treated by endocardial cryotherapy. Catheter Cardiovasc Interv 2003;60:229–232. © 2003 Wiley‐Liss, Inc.
Modified T‐stenting technique with crushing for bifurcation lesions: Immediate results and 30‐day outcome
Authors: Colombo Antonio , Stankovic Goran , Orlic Dejan , Corvaja Nicola , Liistro Francesco , Airoldi Flavio , Chieffo Alaide , Spanos Vassilis , Montorfano Matteo , Di Mario Carlo 
Published: September 2003

AbstractWe report a new stenting technique employed in 20 consecutive patients to treat true bifurcation lesions using the Cypher stent (Cordis, Warren, NJ). Both stents are advanced at the site of the bifurcation. The proximal marker of the side‐branch stent must be situated in the main branch at a distance of 4–5 mm proximal to the carina of the bifurcation and the main branch stent must cover the bifurcation as well as the protruding segment of the side‐branch stent. The side‐branch stent is deployed first and balloon and wire are removed. The stent deployed in the main branch completely covers and crushes the protruding segment of the side branch stent against the vessel wall of the main branch. Following main‐ and side‐branch predilatation, stents were successfully deployed in all lesions. Final kissing balloon inflation was performed in seven patients. Two patients had in‐hospital myocardial infarction and one patient underwent in‐hospital re‐PTCA due to a dissection distal to a stent. No other major adverse cardiac events were observed in‐hospital and during 1‐month clinical follow‐up. Treatment of bifurcation lesions using crushing stent technique is feasible with acceptable rate of procedural complications. Angiographic follow‐up is necessary to prove the advantage of this specific technique to give complete coverage of the ostium of the side branch with a drug‐eluting stent. Catheter Cardiovasc Interv 2003;60:145–151. © 2003 Wiley‐Liss, Inc.
Neonatal transcatheter occlusion of a large coronary artery fistula with Amplatzer duct occluder
Authors: Khan Mohammad D. , Qureshi Shakeel A. , Rosenthal Eric , Sharland Gurleen K. 
Published: September 2003

AbstractA large fistula from the right coronary artery to the right atrium was diagnosed in a fetus at 22 weeks of gestation. Following delivery, the baby developed cardiac failure. The fistula was occluded at 3 weeks of age by transcatheter implantation of an Amplatzer duct occluder. Large coronary fistulas can be closed safely with a device even at this early age. Vigilance for ischemic events is required following implantation because of the rare possibility of thrombus extension proximally into the native coronary artery or spasm of the coronary artery. Catheter Cardiovasc Interv 2003;60:282–286. © 2003 Wiley‐Liss, Inc.
Large pseudoaneurysm after left main trunk stenting sealed by polytetrafluorethylene‐covered stent
Authors: Nameki Mizuo , Ishiwata Sugao , Momomura Shin‐ichi 
Published: September 2003

AbstractLeft main trunk (LMT) aneurysm is very rare and the management remains uncertain. We describe a patient who developed a pseudoaneurysm from coronary perforation during stent implantation in LMT and was then treated with polytetrafluorethylene (PTFE)‐covered stent graft. PTFE‐covered stent is considered to be a valid strategy for LMT aneurysms. Catheter Cardiovasc Interv 2003;60:233–235. © 2003 Wiley‐Liss, Inc.
Percutaneous closure of a giant coronary arteriovenous fistula using multiple devices in a 12‐day‐old neonate
Authors: Holzer Ralf , Waller B. Rush , Kahana Madelyn , Hijazi Ziyad M. 
Published: September 2003

AbstractCoronary arteriovenous fistulas (CAVFs) are uncommon in children and are rarely reported in neonates. Larger fistulas usually require either surgical closure or percutaneous closure using a variety of different devices. Device closure of large fistulas in the immediate neonatal period has not been reported. We report the first case of a gigantic CAVF in a 12‐day‐old neonate (2.4 kg) where successful device closure was achieved in a staged approach using a 12 mm Amplatzer muscular VSD device, seven flipper coils, a 10/8 mm Amplatzer duct occluder device, as well as a 9 mm Gianturco Grifka vascular occlusion device. No complications were encountered and the patient was subsequently weaned off the ventilator. Catheter Cardiovasc Interv 2003;60:291–294. © 2003 Wiley‐Liss, Inc.
Bare delivery of medium and large stents in patients with congenital heart disease
Authors: Vance Michael S. 
Published: September 2003

AbstractThe medium and large stents favored by pediatric cardiologists are typically delivered through a long sheath placed distal to the target lesion. However, long sheath placement can be problematic. The aim of the study was to determine whether stents can be safely delivered without using a long sheath in patients with congenital heart disease. Between July 2001 and October 2002, primary bare stent delivery was attempted in 17 consecutive patients with 21 target lesions. All 21 stents were successfully delivered without employing a long sheath. The series demonstrates that medium and large stents can be safely delivered without a long sheath in patients with congenital heart disease. Furthermore, eliminating the long sheath can improve stent delivery and allow new options when addressing bifurcation lesions. Catheter Cardiovasc Interv 2003;60:276–281. © 2003 Wiley‐Liss, Inc.
Reversal of the direction of internal carotid artery blood flow by occlusion of the common and external carotid arteries in a swine model
Authors: Bates Mark C. , Dorros Gerald , Parodi Juan , Ohki Takao 
Published: September 2003

AbstractIn a swine model, blood flow direction [antegrade (+) and retrograde (−)] and velocity were defined within the common (CCA), internal (ICA), and external (ECA) carotid arteries during CCA occlusion with and without ECA occlusion and blood aspiration. In seven anesthetized swine, Doppler recordings of blood flow direction and velocity were performed in the CCA, ICA, and ECA, before and after vessel(s) occlusion, and after passively and actively induced reversal of blood flow direction. Baseline ICA and ECA blood flow direction and velocities were 92 ± 4 and 90 ± 3 cm/sec; and, with CCA occlusion, the ICA velocity decreased to 30 ± 2 cm/sec (P < 0.001). No flow (zero velocity) occurred with CCA and ECA occlusion. An artificial femoral arteriovenous fistula's continuous gradient passively reversed ICA blood flow direction (−), with the recorded blood's velocity (−24 ± 4 cm/sec) increasing with continuous active aspiration to −90 ± 6 cm/sec. Occlusion of the CCA occlusion alone was unable completely to halt ICA antegrade blood flow direction, while CCA and ECA occlusion completely stopped ICA antegrade flow. CCA and ECA occlusion, when coupled with an arteriovenous fistula arteriovenous and/or aspiration, resulted in ICA blood flow direction reversal, whose velocity could be actively augmented.Catheter Cardiovasc Interv 2003;60:270–275. ©2003Wiley‐Liss,Inc.
Initial experience with a new 8 French‐compatible directional atherectomy catheter: Immediate and mid‐term results
Authors: Orlic Dejan , Reimers Bernhard , Stankovic Goran , Corvaja Nicola , Chieffo Alaide , Airoldi Flavio , Spanos Vassilis , Favero Luca , Di Mario Carlo , Colombo Antonio 
Published: September 2003

AbstractThe purpose of this study was to evaluate the safety and efficacy of the new Fox Hollow atherectomy device (FHT) designed for more efficient and easier plaque removal. The FHT has short rigid section and low‐profile cutter mounted on a monorail catheter. The FHT catheter was utilized in 77 patients with 98 lesions. Mean reference vessel diameter was 2.75 ± 0.51 mm. Successful atherectomy with tissue retrieval was performed in 94 lesions (96%). Following atherectomy, mean diameter stenosis was reduced from 71.1% to 31.9% and further to 10.4% following adjunctive treatment. Angiographic complications were one coronary perforation and one adventitial staining, both successfully treated with prolong balloon inflation and stent implantation. Nine patients (11.7%) had in‐hospital non‐Q‐wave myocardial infarction (MI). One patient died (1.3%) for noncardiac reasons and one had MI (1.3%) at 6‐month follow‐up. Target lesion revascularization was required in 13 (13.8%) lesions and target vessel revascularization in 15 (20.3%) patients. There was target vessel failure in 17 (23.0%) patients. Plaque debulking with the FHT catheter can be performed safely and effectively in relatively small vessels and complex lesions located in mid‐distal artery segments with 6‐month clinical outcome similar to prior atherectomy devices. Catheter Cardiovasc Interv 2003;60:159–166. © 2003 Wiley‐Liss, Inc.