bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations Conferring Resistance to a Potent Hepatitis C Virus Serine Protease Inhibitor In Vitro
Authors: Lu Liangjun , Pilot-Matias Tami J. , Stewart Kent D. , Randolph John T. , Pithawalla Ron , He Wenping , Huang Peggy P. , Klein Larry L. , Mo Hongmei , Molla Akhteruzzaman 
Published: May 2004

ABSTRACT
BILN 2061 is a novel, specific hepatitis C virus (HCV) NS3 serine protease inhibitor discovered by Boehringer Ingelheim that has shown potent activity against HCV replicons in tissue culture and is currently under clinical investigation for the treatment of HCV infection. The poor fidelity of the HCV RNA-dependent RNA polymerase will likely lead to the development of drug-resistant viruses in treated patients. The development of resistance to BILN 2061 was studied by the in vitro passage of HCV genotype 1b replicon cells in the presence of a fixed concentration of the drug. Three weeks posttreatment, four colonies were expanded for genotypic and phenotypic characterization. The 50% inhibitory concentrations of BILN 2061 for these colonies were 72- to 1,228-fold higher than that for the wild-type replicon. Sequencing of the individual colonies identified several mutations in the NS3 serine protease gene. Molecular clones containing the single amino acid substitution A156T, R155Q, or D168V resulted in 357-fold, 24-fold, and 144-fold reductions in susceptibility to BILN 2061, respectively, compared to the level of susceptibility shown by the wild-type replicon. Modeling studies indicate that all three of these residues are located in close proximity to the inhibitor binding site. These findings, in addition to the three-dimensional structure analysis of the NS3/NS4A serine protease inhibitor complex, provide a strategic guide for the development of next-generation inhibitors of HCV NS3/NS4A serine protease.
Anti-Hepatitis B Virus Activity of ORI-9020, a Novel Phosphorothioate Dinucleotide, in a Transgenic Mouse Model
Authors: Iyer Radhakrishnan P. , Roland Arlene , Jin Yi , Mounir Samir , Korba Brent , Julander Justin G. , Morrey John D. 
Published: May 2004

ABSTRACT

ORI-9020, a novel dinucleotide, evaluated in transgenic mice expressing hepatitis B virus (HBV), significantly reduced liver HBV DNA (
P
≤ 0.001). Levels of HBeAg and HBsAg in serum and of HBcAg in liver were not affected by treatment. A minimal effective dosage was determined to be between 1.6 and 0.5 mg/kg of body weight/day, which was similar to that observed for adefovir dipivoxil.
Lack of Effect of Recombinant Human Growth Hormone on the In Vitro Activities of Antiretroviral Drugs against Human Immunodeficiency Virus Type 1
Authors: Wainberg Mark A , Brenner Bluma G. , Daar Eric , Gertner Joseph M. , Olivier Clement , Kenley Susan 
Published: May 2004

ABSTRACTWe studied the effects of recombinant human growth hormone (r-hGH) on human immunodeficiency virus type 1 replication by growing both wild-type and drug-resistant variants of virus in the presence of various concentrations of eight different antiretroviral drugs. r-hGH had no significant effect on either viral replication or the 50% inhibitory concentrations of these compounds.
Validity of Queen’s College step test for use with young Indian men
Authors: Chatterjee S , Chatterjee P , Mukherjee P S , Bandyopadhyay A 
Published: May 2004

Objectives:To assess the suitability of the Queen’s College step test (QCT) to predict maximum oxygen uptake in Indian men.Methods:Thirty sedentary male university students from West Bengal, India, with the same socioeconomic background and mean (SD) age, height, and weight of 22.6 (0.2) years, 166.4 (0.5) cm, and 53.8 (0.2) kg, respectively, were randomly sampled from University of Calcutta. VO2max of each participant was determined by direct procedure involving incremental bicycle exercise and also by applying indirect QCT method with a gap of 4 days between the tests.Results:The difference between the mean (SD) VO2max values directly measured (VO2max = 39.8 (1.03) ml/min/kg body mass) and indirectly predicted (PVO2max = 39.3 (1.07) ml/min/kg body mass) was statistically insignificant (p>0.10). PVO2max and VO2max values expressed as ml/min/kg body mass corroborated with previous studies in the same laboratory involving the same population, and also exhibited significant statistical correlation (r = 0.95, p<0.001) between them.Conclusion:The results suggest that QCT can be applied in the studied population to produce a good estimation of maximum oxygen uptake, especially in the field where large numbers of participants are to be evaluated without a well equipped laboratory.
Epidemiology of injuries in adventure racing athletes
Authors: Fordham S , Garbutt G , Lopes P 
Published: May 2004

Objectives:To assess the demographics and training characteristics of adventure racing athletes in the United Kingdom, the prevalence and anatomical distribution of hazardous encounter, and overuse injury in this population, and the effects these injuries have on training.Methods:A retrospective training and injury questionnaire for the previous 18 months was distributed to 300 adventure racing athletes at two national race meetings. The definition of an injury was “any musculoskeletal problem causing a stop in training for at least one day, reduction in training mileage, taking of medicine, or seeking of medical aid.”Results:The data were derived from the responses of 223 athletes. Advanced level athletes did 11 (4) sessions and 17 (8) hours of training a week (mean (SD)). An injury was reported in the previous 18 months by 73% of the respondents. The most common site of acute injury was the ankle (23%) and of chronic/overuse injury, the knee (30%), followed by the lower back, shin, and Achilles tendon (12% each). There were significant correlations (p<0.01) between the hours spent cycling per week and number of acute injuries, and between the number of days off per week and number of chronic/overuse injuries. Injuries resulted in an average of 23 days training cessation or reduction.Conclusions:Acute injuries were sustained mainly as a result of the nature of the terrain over which athletes train and compete. In overuse injuries lack of adequate rest days was a significant contributing factor. Only a small proportion of training time was spent developing flexibility and core stability.
Effects of 20 days of bed rest on the viscoelastic properties of tendon structures in lower limb muscles
Authors: Kubo K , Akima H , Ushiyama J , Tabata I , Fukuoka H , Kanehisa H , Fukunaga T 
Published: May 2004

Objectives:The purpose of this study was to investigate the effects of 20 days’ bed rest on the viscoelastic properties of human tendon structures in knee extensor and plantar flexor muscles in vivo.Methods:Eight healthy men (age: 24±4 years, height: 172±9 m, body mass: 69±13 kg) carried out a 6° head-down bed rest for 20 days. Before and after bed rest, elongation (L) of the tendon and aponeurosis of vastus lateralis (VL) and medial gastrocnemius muscles (MG) during isometric knee extension and plantar flexion, respectively, were determined using real-time ultrasonic apparatus, while the subjects performed ramp isometric contraction up to the voluntary maximum, followed by ramp relaxation. The relationship between estimated muscle force (Fm) and tendon elongation (L) was fitted to a linear regression, the slope of which was defined as stiffness. The hysteresis was calculated as the ratio of the area within the Fm-L loop to the area beneath the load portion of the curve.Results:L values above 100 N were significantly greater after bed rest for VL, while there were no significant differences in L values between before and after for MG. The stiffness decreased after bed rest for VL (70.3±27.4v50.1±24.8 N/mm, before and after bed rest, respectively; p = 0.003) and MG (29.4±7.5v25.6±7.8 N/mm, before and after bed rest, respectively; p = 0.054). In addition, hysteresis increased after bed rest for VL (16.5±7.1%v28.2±12.9%, before and after bed rest, respectively; p = 0.017), but not for MG (17.4±4.4%v17.7±6.1%, before and after bed rest, respectively; p = 0.925).Conclusions:These results suggested that bed rest decreased the stiffness of human tendon structures and increased their hysteresis, and that these changes were found in knee extensors, but not the plantar flexors.
From the Editor
Authors: Kelton W. David 
Published: May 2004

The very name of JOC suggests that we should be on the cutting edge of technology when it comes to disseminating research, as well as in the content of the work itself. One aspect of this is our growing repository of Online Supplements housed permanently on our website. As I write this, there are some 17 supplements supporting 18 papers, and several more are in development. I invite you to peruse them for a flavor of the kinds of things that we’re able to do in JOC. They include voluminous material for which we don’t have room in the papers themselves, as well as a wide variety of other information in forms not amenable to inclusion in the papers, like downloadable code, data sets, and links to other sites. And as a purely practical budgetary matter, the Online Supplements allow us to shorten some papers, thus making room for more research to appear closer to the completion of the actual work, without impeding access. (It’s hard to imagine any JOC readers at all without ready Internet access.) If you’re an author, you might also think about creative ways to enhance your papers via this medium . . . we’re certainly game to try out new ideas. The Summer 2004 and Fall 2004 issues will focus our attention on the growing and critically important field of biology and on what our community has to offer the exciting prospects there. The Summer 2004 issue will begin with a state-ofthe- art survey on the topic, and the Fall 2004 issue will be a Special Issue devoted entirely to biology. Founding Editor-in-Chief Harvey Greenberg has been the driving force behind both of these efforts. Also in development is a special issue on OR in electrical and computer engineering, guest-edited by John Chinneck. And a special cluster of papers on computation in music will be guest-edited by Elaine Chew. So, running the gamut from electrical engineering to biology to music, we are definitely charting new directions in OR and CS, as our tag line claims. After many years of service as an Associate Editor working primarily in the Telecommunications & Electronic Commerce Area, Rita Vachani has decided to rotate off at this time, and we thank her very much for her fine work for JOC. We welcome Edmund K. Burke of the University of Nottingham as a new Associate Editor, serving primarily in the Heuristic Search and Learning Area, especially on metaheuristics. And we are also happy to have Leyuan Shi of the University of Wisconsin-Madison as a new Associate Editor for our Simulation Area.
Association Between Acetaminophen or Nonsteroidal Antiinflammatory Drugs and Risk of Developing Ovarian, Breast, or Colon Cancer
Authors: Meier Christoph R. , Schmitz Stephen , Jick Hershel 
Published: May 2004

Study Objective. To explore the association between exposure to acetaminophen (paracetamol) or nonsteroidal antiinflammatory drugs (NSAIDs) and risk of developing ovarian, breast, or colon cancer.Design. Retrospective case‐control study.Setting. General practice offices.Subjects. Four hundred eighty‐three women with ovarian cancer and 1877 women matched for age, years of medical history in computer record, general practice attended, and calendar time; 3706 women with breast cancer and 14,155 matched control subjects; and 635 women with colon cancer and 2434 matched control subjects.Intervention. United Kingdom‐based General Practice Research Database was searched for women aged 50–89 years with a first‐time diagnosis of ovarian, breast, or colon cancer and for matched controls to assess prescription analgesic exposure.Measurements and Main Results. Regular acetaminophen exposure (30 prescriptions) was associated with a slightly decreased risk of developing breast (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.7–1.0) but not ovarian (OR 1.0, 95% CI 0.6–1.5) or colon (OR 1.0, 95% CI 0.7–1.4) cancer. Regular NSAID exposure was associated with a reduced risk of colon (OR 0.5, 95% CI 0.3–0.9) but not ovarian or breast cancer.Conclusion. We found no evidence for a decreased ovarian cancer risk for women with regular acetaminophen or NSAID exposure.
Argatroban Dosing in Intensive Care Patients with Acute Renal Failure and Liver Dysfunction
Authors: Williamson David R. , Boulanger Isabelle , Tardif Mariline , Albert Martin , Grégoire Geneviève 
Published: May 2004

Study Objective. To demonstrate dosing adjustment difficulties of argatroban encountered in critically ill patients with acute liver dysfunction who are receiving continuous renal replacement therapy.Design. Case description.Setting. Medical and surgical intensive care unit in a tertiary care, university‐affiliated hospital.Patients. Four consecutive patients with proven heparin‐induced thrombocytopenia (HIT), acute renal failure requiring continuous renal replacement therapy, and various levels of transient hepatic impairment.Intervention. Argatroban, a direct synthetic thrombin inhibitor, was given continuously and stabilized at 0.125–0.85 μg/kg/minute to attain an activated partial thromboplastin time (aPTT) 1.5–2.5 times the normal value for periods of 6–36 days.Measurements and Results. Argatroban was started at the usual dosage of 2 μg/kg/minute, which resulted in significant overshooting of the aPTT and international normalized ratio (INR). No patient experienced bleeding or thrombotic complications. All patients were stabilized with reduced dosages such as those recommended for patients with chronic hepatic impairment.Conclusion. We recommend argatroban therapy for intensive care patients with HIT, especially those with renal failure. However, in all patients with suspected liver dysfunction due to recent elevation of liver transaminase levels and combined renal failure, a decrease in the initial dosage and careful titration of the infusion are mandatory. Further studies are needed to fully elucidate argatroban elimination and dosage adjustments for intensive care patients.
Re‐evaluation of distillation and comparison with HNO3 leaching/solvent extraction for isolation of methylmercury compounds from sediment/soil samples
Authors: Liang Lian , Horvat Milena , Feng Xinbin , Shang Lihai , Li Hao , Pang Patrick 
Published: May 2004

AbstractDistillation was re‐evaluated for the formation of artifacts arising from increasing naturally occurring mercury(II) concentrations, as opposed to previous identification of artifacts by spiking standard mercury(II) into samples. Naturally occurring mercury(II) concentrations lower than 2 µg g−1 were found not to affect methylmercury (MeHg) results. However, when the natural concentrations of mercury(II) were greater than 2 µg g−1, in contrast to standard mercury(II) spiked in samples, the MeHg concentrations measured were found to decrease (not increase) with increasing naturally occurring mercury(II) concentrations. This indicated that standard mercury(II) spiked in samples behaved differently from naturally occurring mercury(II) in the formation of MeHg artifacts during distillation. As a result, spiking standard mercury(II) into samples to identify the formation of MeHg artifacts is not adequate. It is difficult to explain why high naturally occurring mercury(II) suppresses MeHg measurements during distillation. In comparison with HNO3 leaching/solvent extraction (and other existing techniques), distillation was found to generate results comparable for samples containing less than 2 µg g−1 mercury(II). The HNO3 leaching/solvent extraction showed significant advantages over other procedures, as this technique generated the highest recoveries with good precision for all samples analyzed, and the results were found to be independent of mercury(II) concentrations for both naturally occurring and spiked standard mercury(II). Thus, except for samples from high mercury‐contaminated fields, distillation is still a good choice. Both the positive bias (possibly caused by artifact formation of MeHg) and the negative bias (due to incomplete leaching, back‐adsorption, and/or decomposition of MeHg) were investigated. Geologically, physically, and chemically different samples were used for the investigation. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: The [bis(η5‐cyclopentadienyl)titanium(IV)‐bis(L‐methionine)] dichloride
Authors: Bína Radim , Císařová Ivana , Pavlišta Martin , Pavlík Ivan 
Published: May 2004

AbstractThe structure of ionic complex [Cp2Ti(L‐Met)2]2+[Cl−]2 (where Cp = η5‐C5H5) possessing C2 symmetry is presented. Discrete cationic units with distorted tetrahedral geometry around the central titanium atom are connected through intermolecular H···Cl bonds between ammonium group protons of α‐amino acid ligands and chloride anions. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanism of the controlled radical polymerization of styrene and methyl methacrylate in the presence of dicyclopentadienyltitanium dichloride
Authors: Grishin Dmitry F. , Ignatov Stanislav K. , Shchepalov Alexander A. , Razuvaev Alexey G. 
Published: May 2004

AbstractThe mechanism of the controlled radical polymerization of styrene and methyl methacrylate in the presence of dicyclopentadienyltitanium dichloride (Cp2TiCl2) was studied using quantum chemical calculations and electron spin resonance spectroscopy. It was established that the reduction of Cp2TiCl2 to Cp2TiCl during the macromolecule synthesis occurs through the living polymerization mechanism, which adjusts the growth of a polymeric chain. The geometrical structures of the molecular complexes between a growing macroradical and Cp2TiCl2 and transition states of radical inhibition steps were optimized and the thermodynamic and kinetic parameters of the elementary reactions were estimated for several feasible directions of the process. On this basis, the observed kinetic features of vinylic monomer polymerization with participation of organic compounds of titanium are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Preparation, characterization and catalytic oxidation properties of tris[2‐(2‐pyridyl)benzimidazole]iron(II) complexes
Authors: Wang Mei , Sun Hongfei , Wang Yu , Wang Xiuna , Li Fei , Sun Licheng 
Published: May 2004

AbstractComplexes [Fe(Hpbi)3](ClO4)2 (1) and [Fe(Hpbi)3](SbF6)2 (2) (Hpbi = 2‐(2‐pyridyl)benzimidazole) were prepared by a modified method and characterized by IR, 1H and 13C NMR, mass spectrometry, electron paramagnetic resonance spectra and elemental analysis. The catalytic activities of 1 and 2 were evaluated for the oxidation of cyclohexene, cyclohexane, ethylbenzene and adamantane with tert‐butylhydroperoxide or H2O2 as oxidant, and the results were compared with the properties of their analogue [Fe(bpy)3](SbF6)2 (3). Complexes 1 and 2 both afforded the ketonization product for the oxidation of ethylbenzene and the hydroxylation product for adamantane. Copyright © 2004 John Wiley & Sons, Ltd.
Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention
Authors: Bellandi Francesco , Maioli Mauro , Gallopin Michela , Toso Anna , Dabizzi Roberto Piero 
Published: May 2004

AbstractIn this prospective randomized trial on patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI), we hypothesized that abciximab administered intracoronarily, downstream of the coronary occlusion, leads to a greater degree of myocardial salvage and better left ventricular function recovery compared with the usual abciximab administration. Forty‐five consecutive patients with first AMI and infarct‐related artery TIMI flow 0–1 undergoing primary PCI were enrolled. Twenty‐two patients were randomly assigned to the intracoronary treatment and 23 to the usual treatment. The initial perfusion defect, final infarct size, myocardial salvage, salvage index, and left ventricular function recovery were assessed by serial scintigraphic scans performed at admission and 7 days and 1 month after PCI. Angiographic myocardial blush grade, corrected TIMI frame count, and electrocardiographic ST segment elevation reduction were also assessed as markers of myocardial reperfusion. Final infarct size was significantly smaller (P = 0.043) and salvage index significantly higher (P = 0.003) in the intracoronary treatment group as a result of a greater degree of myocardial salvage (P = 0.0001). The increase of left ventricular ejection fraction at 1 month was significantly higher in the intracoronary treatment patients (P = 0.013). The markers of myocardial reperfusion were also significantly better in the intracoronary treatment group. In patients with AMI and occluded infarct‐related artery treated with primary PCI, intracoronary abciximab given just before PCI downstream of the occlusion is associated to a greater degree of myocardial salvage than the usual abciximab protocol. This benefit is mainly related to a substantial reduction in final infarct size, which leads to an improvement in left ventricular ejection fraction. Catheter Cardiovasc Interv 2004;62:186–192. © 2004 Wiley‐Liss, Inc.
Device closure of iatrogenic membranous ventricular septal defects after prosthetic aortic valve replacement using the Amplatzer membranous ventricular septal defect occluder
Authors: Holzer Ralf , Latson Larry , Hijazi Ziyad M. 
Published: May 2004

AbstractIatrogenic hemodynamically significant ventricular septal defects (VSDs) after aortic valve replacement are rare. The surgical risk to close such VSDs is substantial. Catheter closure has rarely been attempted because access to the left ventricle during cardiac catheterization in patients with a prosthetic aortic valve has been associated with a risk of catheter entrapment. We describe two cases of this rare entity after St. Jude and Medtronic valve replacement in which successful percutaneous closure of the iatrogenic VSDs was achieved using the Amplatzer membranous VSD occluder. Crossing the prosthetic valves with a delivery sheath and closure with the membranous VSD device was accomplished in both cases. Catheter Cardiovasc Interv 2004;62:276–280. © 2004 Wiley‐Liss, Inc.
Bivalirudin‐associated intracoronary thrombosis during γ‐brachytherapy and its experimental validation in acute swine model
Authors: Kuchulakanti Pramod K. , Satler Lowell F. , Rha Seung‐Woon , Waksman Ron 
Published: May 2004

AbstractBivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with β‐radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with γ‐radiation when bivalirudin is used. Catheter Cardiovasc Interv 2004;62:209–213. © 2004 Wiley‐Liss, Inc.
Double‐wire technique for access into a protruding aorto‐ostial stent for treatment of in‐stent restenosis
Authors: Chetcuti Stanley J. , Moscucci Mauro 
Published: May 2004

AbstractWe report a case of restenosis following ostial stenting of the right coronary artery with protrusion of the stent into the aorta. Treatment was only possible after a guidewire advanced through a lower strut was used to lever the guide, and a second guidewire was advanced through the true lumen. Catheter Cardiovasc Interv 2004;62:214–217. © 2004 Wiley‐Liss, Inc.