bluuebunny/crossref_metadata_2025_split huggingface dataset:
BiasViz: visualization of amino acid biased regions in protein alignments
Authors: Huska Matthew R. , Buschmann Henrik , Andrade-Navarro Miguel A. 
Published: October 2007

AbstractSummary: About a third of all protein sequences have at least one composition biased region (CBR). Such regions might act as linkers between protein domains but often confer specific binding to various molecules; therefore, their characterization in terms of their boundaries and over-represented residues is important. Analysis of CBRs in a particular sequence can be time consuming if several types of biases have to be explored and their position visualized. Assessment of the significance of the detected CBRs can be approached by comparison to homologous protein sequences. To assist this procedure, we have developed BiasViz, a tool that allows to graphically studying local amino acid composition in protein sequences of a multiple sequence alignment.Availability: BiasViz java applet and source code can be accessed from http://biasviz.sourceforge.netContact: matthuska@alumni.uwaterloo.ca
HMM-Kalign: a tool for generating sub-optimal HMM alignments
Authors: Becker Emmanuelle , Cotillard Aurélie , Meyer Vincent , Madaoui Hocine , Guérois Raphaël 
Published: October 2007

AbstractSummary: Recent development of strategies using multiple sequence alignments (MSA) or profiles to detect remote homologies between proteins has led to a significant increase in the number of proteins whose structures can be generated by comparative modeling methods. However, prediction of the optimal alignment between these highly divergent homologous proteins remains a difficult issue. We present a tool based on a generalized Viterbi algorithm that generates optimal and sub-optimal alignments between a sequence and a Hidden Markov Model. The tool is implemented as a new function within the HMMER package called hmmkalign.Availability: http://www-spider.cea.fr/Groups/hk3039/view.htmlSupplementary information: Supplementary data are available at Bioinformatics online.
Genetic Diversity of Lettuce for Resistance to Bacterial Leaf Spot Caused by Xanthomonas campestris pv. vitians
Authors: Bull Carolee T. , Goldman Polly H. , Hayes Ryan , Madden Laurence V. , Koike Steven T. , Ryder Ed 
Published: October 2007

Lettuce plants were artificially inoculated with three isolates of Xanthomonas campestris pv. vitians in field and greenhouse evaluations for genetic variation in resistance to bacterial leaf spot. The cultivar Little Gem had the least amount of disease, whether evaluated for disease severity or disease incidence. Disease severity levels for cultivar Batavia Reine des Glaces were not significantly different from those of Little Gem. Several cultivars including Vista Verde, Pybas 251, Pacific, Clemente, Salinas 88, and Sniper were highly susceptible. There was a strong correlation between results obtained in the greenhouse and those obtained in the field (r = 0.77, P = 0.009) indicating that greenhouse assays may be used to increase the number of cultivars evaluated and to speed breeding efforts. Accepted for publication 17 May 2007. Published 17 September 2007.
Low concentrations of doxorubicin sensitizes human solid cancer cells to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐receptor (R) 2‐mediated apoptosis by inducing TRAIL‐R2 expression
Authors: Wu Xiu‐Xian , Jin Xing‐Hua , Zeng Yu , El Hamed Ahmed Mamdouh Abd , Kakehi Yoshiyuki 
Published: October 2007

There is accumulating evidence suggesting that tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐receptor (R) 2 is a promising molecular target for cancer therapy. Therefore, we investigated the effect of chemotherapeutic agents on TRAIL‐R2‐mediated apoptosis and cytotoxicity in various human solid cancer cells. Treatment of the ACHN human renal cell carcinoma (RCC) cell line with agonistic TRAIL‐R2 antibody (lexatumumab) in combination with 5‐fluorouracil, vinblastine, paclitaxel, or docetaxel did not overcome resistance to these agents. However, treatment with lexatumumab in combination with doxorubicin had a synergistic cytotoxicity. Synergy was also achieved in two other human RCC cell lines, Caki‐1 and Caki‐2, and in eight primary RCC cell cultures. Sequential treatment with doxorubicin followed by lexatumumab induced significantly more cytotoxicity than reverse treatment or simultaneous treatment. Low concentrations of doxorubicin (0.1 and 1 µg/mL) significantly increased TRAIL‐R2 expression at both the mRNA and protein levels. Furthermore, the combination of doxorubicin and lexatumumab significantly enhanced caspase 8 activity, Bid cleavage, Bcl‐xL decrease, release of cytochrome c, and caspase 9 and caspase 3 activity, and induced synergistic apoptosis. The activation of caspases and apoptosis induced with lexatumumab and doxorubicin was blocked by the human recombinant DR5:Fc chimeric protein. In addition, synergistic cytotoxicity was also observed in human prostate, bladder, and lung cancer cells, but was inhibited by the DR5:Fc chimeric protein. These findings suggest that doxorubicin sensitizes solid cancer cells to TRAIL‐R2‐mediated apoptosis by inducing TRAIL‐R2 expression, and that the combination treatment with lexatumumab and doxorubicin might be a promising targeted therapy for cancers, including RCC, prostate, bladder, and lung cancers. (Cancer Sci 2007; 98: 1969–1976)
Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: management strategies
Authors: Rosencher N. , Bonnet M.‐P. , Sessler D. I. 
Published: October 2007

SummaryWe propose recommendations to reduce the risk of haemorrhagic events associated with regional anaesthesia in patients treated with newer anticoagulants after orthopaedic surgery. The risk/benefit ratio should be individualised for each patient according to the type and dose of anticoagulant, the type of regional anaesthesia and patient risk factors. Neuraxial anaesthetic management strategy can be based on the pharmacokinetic properties of specific anticoagulants, including the time required to reach maximal concentration, half‐life, and dose regimen. Central neuraxial blocks should not be performed and epidural catheters should not be removed until at least two half‐lives after the last injection of anticoagulant, the half‐life depending on renal function. After removing a catheter or after a haemorrhagic puncture, the timing of the next anticoagulant injection should be based on the time required for an anticoagulant dose to reach maximum activity. Vigilance remains paramount during the initial days after removal of a neuraxial catheter.
A prospective randomised double blind study to evaluate the effect of peribulbar block or topical application of local anaesthesia combined with general anaesthesia on intra‐operative and postoperative complications during paediatric strabismus surgery
Authors: Gupta N. , Kumar R. , Kumar S. , Sehgal R. , Sharma K. R. 
Published: October 2007

SummaryWe studied 45 ASA I/II children aged between 2 and 13 years scheduled for elective strabismus surgery, randomly allocated to receive either a peribulbar block or topical lidocaine 2% combined with general anaesthesia, or general anaesthesia alone. The incidence and severity of the occulocardiac reflex, the requirement for atropine, the occurrence of arrhythmias and incidence of postoperative nausea and vomiting following surgery at 1, 2 and 4 h were studied. We found the incidence and severity of occulocardiac reflex intra‐operatively was significantly reduced in children who received a peribulbar block. The incidence of postoperative nausea and vomiting was significantly reduced in patients receiving either peribulbar block or topical local anaesthesia combined with general anaesthesia, compared to general anaesthesia alone (p = 0.008).
The effect of time of day on the duration of neuromuscular blockade elicited by rocuronium*
Authors: Cheeseman J. F. , Merry A. F. , Pawley M. D. M. , De Souza R. L. , Warman G. R. 
Published: October 2007

SummaryIn a prospective, observational trial, we investigated the influence of time of day on the duration of neuromuscular blockade (NMB) elicited by rocuronium. Forty‐nine patients scheduled for surgery between 08:00 and 02:00 were enrolled after giving written informed consent. Time to neuromuscular recovery was measured following three doses: (1) a fat‐free‐mass (FFM) related induction dose (0.6 mg.kg−1: n = 47); (2) a maintenance dose (20% of the induction dose: n = 42); and (3) a standard 10‐mg dose (n = 35). The extent of NMB was dependent on the time of administration (p = 0.038 General Linear Model Analysis). The maximum effect of 50 min (95% CI 41–59 min) was elicited between 08:00 and 11:00 and the minimum duration of 29 min (95% CI 23–35 min) between 14:00 and 17:00 (p = 0.005). A similar pattern was observed for the maintenance dose. The duration of action of rocuronium is influenced by time of day and this effect is of potential clinical significance and practical relevance to research.
Improving the efficiency of the drawover anaesthetic breathing system
Authors: Eales M. , Rowe P. , Tully R. 
Published: October 2007

SummaryWe investigated modifications to the reservoir tube usually used in drawover anaesthetic breathing systems as a method of improving its efficiency and performance. The resulting oxygen concentration was recorded at different oxygen flow rates whilst an artificial lung was being ventilated over a range of minute volumes. Addition of a reservoir bag and valves significantly increased the measured percentage of oxygen at the common gas outlet when compared to a 300‐ml reservoir tube. There was no difference in the percentage of oxygen when comparing a reservoir bag and a 600‐ml reservoir tube.
Effects of continuous remifentanil administration on intra‐operative subcutaneous tissue oxygen tension
Authors: Kabon B. , Kugener A. , Gruenberger T. , Niedermayr M. , Fleischmann E. , Freissmuth M. , Kurz A. 
Published: October 2007

SummarySurgical stress response markedly increases sympathetic nerve activity and catecholamine concentrations. This may contribute to peripheral vasoconstriction, reduced wound perfusion and subsequent tissue hypoxia. Opioids are known to depress the hypothalamic‐adrenal response to surgery in a dose‐dependent manner. We tested the hypothesis that continuous remifentanil administration produces improved subcutaneous tissue oxygen tension compared to fentanyl bolus administration. Forty‐six patients undergoing major abdominal surgery were randomly assigned to receive either fentanyl bolus administration or continuous remifentanil infusion. Mean subcutaneous tissue oxygen values over the entire intra‐operative period were significantly higher in the remifentanil group, when compared to the fentanyl group: 8 (2) kPa vs 6.7 (1.5) kPa, % CI difference: − 2.3 kPa to − 0.3 kPa, p = 0.013. Continuous intra‐operative opioid administration may blunt vasoconstriction caused by surgical stress and adrenergic responses more than an equi‐effective anaesthetic regimen based on smaller‐dose bolus opioid administration.
Relative lung deposition of salbutamol following inhalation from a spacer and a Sidestream jet nebulizer following an acute exacerbation
Authors: Mazhar Syed H. R. , Ismail Nahlah E. , Newton Duncan A. G. , Chrystyn Henry 
Published: October 2007

What is already known about this subject • Studies have shown that a large volume spacer attached to a metered dose inhaler provides similar bronchodilator effects to nebulized dosing during the management of patients following an acute exacerbation.• Due to the high doses used, these effects could be measured at the top of the dose–response relationship and the response limited due to the patient's exacerbation.• Although clinical end‐points are the gold standard to show comparability, some indication of similar lung deposition is useful to consolidate any claims. What this study adds • The urinary pharmacokinetic method we have used postinhalation provides an index of lung deposition for inhalation methods that can be incorporated into the routine management of patients with an acute exacerbation.• This is the first study to identify and compare lung deposition and systemic delivery for inhalation methods within the setting of the routine management of asthma and chronic obstructive pulmonary disease patients following hospitalization due to an acute exacerbation.• The study highlights the comparability of the doses for the two inhalation methods evaluated with respect to lung deposition, systemic delivery and bronchodilator response.BackgroundStudies comparing inhalation methods in acute exacerbations have not assessed lung deposition.MethodsFive 100‐μg salbutamol doses were inhaled from a metered dose inhaler plus spacer (MDI + SP) and 5 mg was nebulized (NEB) following acute exacerbation hospitalization. Urinary salbutamol excretion was determined at 30 min (USAL0.5) and over 24 h (USAL24) postinhalation together with forced expiratory volume in 1 s (FEV1).ResultsThe USAL0.5 mean ratio (90% confidence interval) post MDI + SP and NEB [n = 19 asthma, 11 chronic obstructive pulmonary disease (COPD)] was 1.01 (0.81, 1.26). USAL24 was less (P < 0.001) following MDI + SP, whereas FEV1 was similar. Only a small difference between asthmatics and COPD patients was observed for the MDI + SP in that the USAL0.5 was higher in the asthmatics for the spacer method.ConclusionThe relative lung deposition after inhaling 500 μg salbutamol from MDI + SP is similar to 5 mg from a Sidestream nebulizer following an acute exacerbation.
Perforated peptic ulcer and short‐term mortality among tramadol users
Authors: Tørring Marie L. , Riis Anders , Christensen Steffen , Thomsen Reimar W. , Jepsen Peter , Søndergaard Jens , Sørensen Henrik T. 
Published: October 2007

What is already known about this subject • Use of nonsteroidal anti‐inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high‐risk patients.• Pain management guidelines propose tramadol as a treatment option for mild‐to‐moderate pain in patients at high risk of gastrointestinal side‐effects, including peptic ulcer disease.• Tramadol may mask symptoms of peptic ulcer complications, yet tramadol's effect on peptic ulcer prognosis is unknown. What this study adds • In this population‐based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs.• Among users of tramadol, alone or in combination with NSAIDs, adjusted 30‐day mortality rate ratios were 2.02 [95% confidence interval (CI) 1.17, 3.48] and 1.32 (95% CI 0.89, 1.95), compared with patients who used neither tramadol nor NSAIDs.AimUse of nonsteroidal anti‐inflammatory drugs (NSAIDs) increases risk and worsens prognosis for patients with complicated peptic ulcer disease. Therefore, patients who are at high risk of peptic ulcer often use tramadol instead of NSAIDs. Tramadol's effect on peptic ulcer prognosis is unknown. The aim was to examine mortality in the 30 days following hospitalization for perforated peptic ulcer among tramadol and NSAID users compared with non‐users.MethodsThe study was based on data on reimbursed prescriptions and hospital discharge diagnoses for the 1993–2004 period, extracted from population‐based healthcare databases. All patients with a first‐time diagnosis of perforated peptic ulcer were identified, excluding those with previous ulcer diagnoses or antiulcer drug use. Cox regression was used to estimate 30‐day mortality rate ratios for tramadol and NSAID users compared with non‐users, adjusting for use of other drugs and comorbidity.ResultsOf 1271 patients with perforated peptic ulcers included in the study, 2.4% used tramadol only, 38.9% used NSAIDs and 7.9% used both. Thirty‐day mortality was 28.7% overall and 48.4% among users of tramadol alone. Compared with the 645 patients who used neither tramadol nor NSAIDs, the adjusted mortality rate in the 30 days following hospitalization was 2.02‐fold [95% confidence interval (CI) 1.17, 3.48] higher for the 31 ‘tramadol only’ users, 1.41‐fold (95% CI 1.12, 1.78) higher for the 495 NSAID users and 1.32‐fold (95% CI 0.89, 1.95) higher for the 100 patients who used both drugs.ConclusionAmong patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs.
Effects of smoking cessation, acute re‐exposure and nicotine replacement in smokers on AIR® inhaled insulin pharmacokinetics and glucodynamics
Authors: Pan Alan X. , De La Peña Amparo , Yeo Kwee P. , Chan Clark , Loh Mei T. , Wise Stephen D. , Silverman Bernard L. , Muchmore Douglas B. 
Published: October 2007

What is already known about this subject • Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the risk for hypoglycaemia and thus should not be used by active smokers. What this study adds • This is the first euglycaemic clamp study on the impact of smoking cessation, acute smoking re‐exposure and nicotine replacement on AIR® inhaled insulin pharmacokinetics and glucodynamics.• We demonstrate clinically and statistically significant shifts in glucodynamic response to acute re‐exposure to a single cigarette, leading us to conclude that active smokers should be advised against inhaled insulin therapy until smoking abstinence is stable.• Additionally, these results are also the first to demonstrate an apparent independent effect of nicotine replacement therapy on insulin exposure and glucodynamic response.AimsTo explore the effects of smoking cessation and acute smoking re‐exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR® inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT).MethodsNondiabetic smokers (n = 24) with normal pulmonary function completed a two‐phase (four‐period), open‐label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8–12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4‐week smoking‐cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re‐exposure on inhaled insulin PK and GD.ResultsCompared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4‐week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced.ConclusionSmoking, smoking cessation and acute re‐exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism.
Chronic lymphocytic leukaemia and radiation: findings among workers at five US nuclear facilities and a review of the recent literature
Authors: Schubauer‐Berigan Mary K. , Daniels Robert D. , Fleming Donald A. , Markey Andrea M. , Couch James R. , Ahrenholz Steven H. , Burphy Jenneh S. , Anderson Jeri L. , Tseng Chih‐Yu 
Published: October 2007

SummaryThe aetiology of chronic lymphocytic leukaemia (CLL) is largely unknown. Despite compelling evidence for ionising radiation as a cause of most forms of leukaemia, CLL was not found to be radiogenic in early studies. Herein we describe the recent evidence for causation of CLL by ionising and non‐ionising radiation, including a nested case‐control study conducted within a cohort of 94 517 US workers at four nuclear weapons facilities and a nuclear naval shipyard. Forty‐three cases of CLL deaths and 172 age‐matched controls were identified with follow‐up up to between 1990 and 1996. Radiation exposure from external sources and plutonium (lagged 10 years) was assessed for each worker, based on monitoring records. The excess relative rate (ERR) was estimated for workers receiving elevated doses compared to unexposed workers, controlling for possible risk factors. The ERR per 10 mSv was −0·020 (95% confidence interval: <0, 0·14) based on all exposed workers. However, for workers receiving <100 mSv, the ERR per 10 mSv was 0·20 (−0·035, 0·96). Recent studies of uranium miners and other populations have shown elevations of CLL possibly associated with ionising and non‐ionising radiation. New studies should use incident cases and sufficient latency to account for the expected lengthy induction period for CLL.
TRAIL signals to apoptosis in chronic lymphocytic leukaemia cells primarily through TRAIL‐R1 whereas cross‐linked agonistic TRAIL‐R2 antibodies facilitate signalling via TRAIL‐R2
Authors: Natoni Alessandro , MacFarlane Marion , Inoue Satoshi , Walewska Renata , Majid Aneela , Knee Deborah , Stover David R. , Dyer Martin J. S. , Cohen Gerald M. 
Published: October 2007

SummaryTumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), a member of the TNF family, which is being developed as an anti‐tumour agent due to its selective toxicity to tumour cells, induces apoptosis by binding to two membrane‐bound receptors, TRAIL‐R1 and TRAIL‐R2. Clinical trials have been initiated with various preparations of TRAIL as well as agonistic monoclonal antibodies to TRAIL‐R1 and TRAIL‐R2. Previously we reported that prior treatment of primary chronic lymphocytic leukaemia (CLL) cells with histone deacetylase inhibitors was required to sensitize CLL cells to TRAIL and, using various receptor‐selective TRAIL mutant ligands, we demonstrated that CLL cells signalled to apoptosis primarily through TRAIL‐R1. Some, but not all, agonistic TRAIL‐receptor antibodies require cross‐linking in order to induce apoptosis. The present study demonstrated that CLL cells can signal to apoptosis through the TRAIL‐R2 receptor, but only after cross‐linking of the agonistic TRAIL‐R2 antibodies, LBY135 and lexatumumab (HGS‐ETR2). In contrast, signalling through TRAIL‐R1 by receptor‐selective ligands or certain agonistic antibodies, such as mapatumumab (HGS‐ETR1), occurs in the absence of cross‐linking. These results further highlight important differences in apoptotic signalling triggered through TRAIL‐R1 and TRAIL‐R2 in primary tumour cells. Such information is clearly important for the rational optimisation of TRAIL therapy in primary lymphoid malignancies, such as CLL.