bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desflurane-induced Preconditioning Alters Calcium-induced Mitochondrial Permeability Transition
Authors: Piriou Vincent , Chiari Pascal , Gateau-Roesch Odile , Argaud Laurent , Muntean Danina , Salles Delphine , Loufouat Joseph , Gueugniaud Pierre-Yves , Lehot Jean-Jacques , Ovize Michel 
Published: February 2004

Background
Recent investigations have focused on the pivotal role of the mitochondria in the underlying mechanisms volatile anesthetic-induced myocardial preconditioning. This study aimed at examining the effect of anesthetic preconditioning on mitochondrial permeability transition (MPT) pore opening.

Methods
Anesthetized open chest rabbits were randomized to one of four groups and underwent 10 min of ischemia, except for the sham 1 group (n = 12). Before this, they underwent a treatment period consisting of (1) no intervention (ischemic group; n = 12), (2) 30 min of desflurane inhalation (8.9% end-tidal concentration) followed by a 15-min washout period (desflurane group; n = 12), or (3) ischemic preconditioning (IPC group; n = 12). A second set of experiments was performed to evaluate the effect of a putative mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate (5-HD). The animals underwent the same protocol as previously, plus pretreatment with 5 mg/kg 5-HD. They were randomized to one of five groups: the sham 2 group, receiving no 5-HD (n = 12); the sham 5-HD group (n = 12); the ischemic 5-HD group (n = 12), the desflurane 5-HD group (n = 12), and the IPC 5-HD group (n = 12). At the end of the protocol, the hearts were excised, and mitochondria were isolated. MPT pore opening was assessed by measuring the amount of calcium required to trigger a massive calcium release indicative of MPT pore opening.

Results
Desflurane and IPC group mitochondria needed a higher calcium load than ischemic group mitochondria (362 +/- 84, 372 +/- 74, and 268 +/- 110 microM calcium, respectively; P < 0.05) to induce MPT pore opening. The sham 1 and sham 2 groups needed a similar amount of calcium to trigger mitochondrial calcium release (472 +/- 70 and 458 +/- 90 microM calcium, respectively). 5-HD preadministration had no effect on sham animals (458 +/- 90 and 440 +/- 128 microM calcium without and with 5-HD, respectively) and ischemic group animals (268 +/- 110 and 292 +/- 102 microM calcium without and with 5-HD, respectively) but abolished the effects of desflurane on calcium-induced MPT pore opening (362 +/- 84 microM calcium without 5-HD vs. 238 +/- 96 microM calcium with 5-HD; P < 0.05) and IPC (372 +/- 74 microM calcium without 5-HD vs. 270 +/- 104 microM calcium with 5-HD; P < 0.05).

Conclusion
Like ischemic preconditioning, desflurane improved the resistance of the transition pore to calcium-induced opening. This effect was inhibited by 5-HD, suggesting a link between mitochondrial adenosine triphosphate-sensitive potassium and MPT.
Reduced Efficacy of Volatile Anesthetic Preconditioning with Advanced Age in Isolated Rat Myocardium
Authors: Sniecinski Roman , Liu Hong 
Published: February 2004

Background
Ischemic preconditioning and anesthetic preconditioning (APC) are reported to decrease myocardial infarct size during ischemia-reperfusion injury. However, the beneficial effects of ischemic preconditioning have been shown to decrease with advancing age. Although the mechanisms of ischemic preconditioning and APC are thought to be similar, it is not known whether the beneficial effects of APC are also reduced in the aged myocardium.

Methods
Male Fischer 344 rats of three age groups (2-4, 10-12, and 20-24 months) were used. Hearts were Langendorff perfused. Six hearts in each age group were pretreated with 10 min of sevoflurane and a 5-min washout before 25 min of ischemia and 60 min of reperfusion. Six control hearts in each age group received no treatment before ischemia. Nuclear magnetic resonance was used to measure intracellular Na, intracellular Ca, and intracellular pH, respectively. Left ventricular developed pressure, creatine kinase, and infarct size were measured.

Results
Ischemia decreases intracellular pH and increases intracellular Na and intracellular Ca in all age groups. APC blunts the pH decreases in young adult and middle-aged rats, but not in aged rats. APC decreased intracellular Na and intracellular Ca accumulation during ischemia in young adult and middle-aged hearts. APC improved adenosine triphosphate recovery in young rats but not in aged rats. Creatine kinase and infarct sizes were significantly reduced and left ventricular developed pressure was improved with APC in the young adult and middle-aged groups but not the aged group.

Conclusions
The benefits of APC are significantly reduced with advanced age in an isolated rat heart model.
Sequential Effects of Increasing Propofol Sedation on Frontal and Temporal Cortices as Indexed by Auditory Event-related Potentials
Authors: Heinke Wolfgang , Kenntner Ramona , Gunter Thomas C. , Sammler Daniela , Olthoff Derk , Koelsch Stefan 
Published: February 2004

Background
It is an open question whether cognitive processes of auditory perception that are mediated by functionally different cortices exhibit the same sensitivity to sedation. The auditory event-related potentials P1, mismatch negativity (MMN), and early right anterior negativity (ERAN) originate from different cortical areas and reflect different stages of auditory processing. The P1 originates mainly from the primary auditory cortex. The MMN is generated in or in the close vicinity of the primary auditory cortex but is also dependent on frontal sources. The ERAN mainly originates from frontal generators. The purpose of the study was to investigate the effects of increasing propofol sedation on different stages of auditory processing as reflected in P1, MMN, and ERAN.

Methods
The P1, the MMN, and the ERAN were recorded preoperatively in 18 patients during four levels of anesthesia adjusted with target-controlled infusion: awake state (target concentration of propofol 0.0 microg/ml), light sedation (0.5 microg/ml), deep sedation (1.5 microg/ml), and unconsciousness (2.5-3.0 microg/ml). Simultaneously, propofol anesthesia was assessed using the Bispectral Index.

Results
Propofol sedation resulted in a progressive decrease in amplitudes and an increase of latencies with a similar pattern for MMN and ERAN. MMN and ERAN were elicited during sedation but were abolished during unconsciousness. In contrast, the amplitude of the P1 was unchanged by sedation but markedly decreased during unconsciousness.

Conclusion
The results indicate differential effects of propofol sedation on cognitive functions that involve mainly the auditory cortices and cognitive functions that involve the frontal cortices.
Influence of Chronic Phenytoin Administration on the Pharmacokinetics and Pharmacodynamics of Vecuronium
Authors: Wright Peter M. C. , McCarthy Gerald , Szenohradszky Janos , Sharma Manohar L. , Caldwell James E. 
Published: February 2004

Background
The duration of action of vecuronium is reduced in patients receiving phenytoin. In this study, the authors examined, simultaneously, the influence of phenytoin on both the pharmacokinetics and the pharmacodynamics of vecuronium.

Methods
This study was approved by the institutional review board of the University of California, San Francisco, and patients gave written informed consent. Twenty-two patients, 11 taking phenytoin and all scheduled to undergo prolonged neurosurgical procedures with general anesthesia, participated in the study. In 12 patients (6 phenytoin, 6 control), vecuronium was infused at 7.5 microg x kg(-1) x min(-1) until the first response (T1) of each train-of-four decreased by 50%; in the remaining 10 patients (5 phenytoin, 5 control), 200 microg/kg vecuronium was infused over 10 min. Arterial blood samples were drawn at intervals over the next 5-7 h. Plasma concentrations of vecuronium and 3-desacetylvecuronium were measured by capillary gas chromatography. Pharmacokinetic and pharmacodynamic modeling was used to characterize the disposition of vecuronium and patient responses to it in the two groups.

Results
Clearance was typically increased by 138% (95% confidence interval, 93-183%) in patients taking phenytoin. The effect of vecuronium was well described using a sigmoid Emax model. The concentration of vecuronium giving 50% twitch depression was increased 124% (45-202%) in patients taking phenytoin.

Conclusions
Chronic phenytoin therapy reduces the effect of vecuronium by mechanisms that include both increased vecuronium metabolism and reduced sensitivity of the patient to circulating concentrations of vecuronium.
Performance Evaluation of Two Published Closed-loop Control Systems Using Bispectral Index Monitoring
Authors: Struys Michel M. R. F. , De Smet Tom , Greenwald Scott , Absalom Anthony R. , Bingé Servaas , Mortier Eric P. 
Published: February 2004

Background
Although automated closed-loop control systems may improve quality of care, their safety must be proved under extreme control conditions. This study describes a simulation methodology to test automated controllers and its application in a comparison of two published controllers for Bispectral Index (BIS)-guided propofol administration.

Methods
A patient simulator was developed to compare controllers. Using input scripts to dictate patient characteristics, target BIS values, and the time course of surgical events, the simulator continuously monitors the infusion pump under control and generates BIS values as a composite of modeled response to drug, perceived stimulation, and random noise. The simulator formats the output stream of BIS data as input to the controller under test to emulate the serial output of the actual BIS monitor. A published model-based controller and a classic proportional integral derivative controller were compared when using the BIS value as a controlled variable. Each controller was tested using a set of 10 virtual patients undergoing a fixed surgical profile that was repeated with BIS targets set at 30, 50, and 70. Controller performance was assessed using median (absolute) prediction error, divergence, wobble, and percentage time within BIS target range metrics.

Results
The median prediction error was significantly smaller for the proportional integral derivative controller than for the model-based controller. The median absolute prediction error was smaller for the model-based controller than for the proportional integral derivative controller for each BIS target, reaching statistical significance for targets 30 and 50.

Conclusions
When simulating closed-loop control of BIS using propofol, the use of a patient-individualized, model-based adaptive closed-loop system with effect site control resulted in better control of BIS compared with a standard proportional integral derivative controller with plasma site control. Even under extreme conditions, the modeled-based controller exhibited no behavioral problems.
Mapping Hsp47 binding site(s) using CNBr peptides derived from type I and type II collagen
Authors: Thomson Christy A. , Tenni Ruggero , Ananthanarayanan Vettai S. 
Published: February 2004

AbstractAs a crucial molecular chaperone in collagen biosynthesis, Hsp47 interacts with the nascent form as well as the mature triple‐helical form of procollagen. The location(s) of Hsp47 binding sites on the collagen molecule are, as yet, unknown. We have examined the substrate specificity of Hsp47 in vitro using well‐characterized CNBr peptide fragments of type I and type II collagen along with radiolabeled, recombinant Hsp47. Interaction of these peptides with Hsp47 bound to collagen‐coated microtiter wells showed several binding sites for Hsp47 along the length of the α1 and α2 chains of type I collagen and the α1 chain of type II collagen, with the N‐terminal regions showing the strongest affinities. The latter observation was also supported by the results of a ligand‐blot assay. Except for two peptides in the α2(I) chain, peptides that showed substantial binding to Hsp47 did so in their triple‐helical and not random‐coil form. Unlike earlier studies that used peptide models for collagen, the results obtained here on fragments of type I and type II collagen identify, for the first time, binding of Hsp47 to specific regions of the collagen molecule. They also point to additional structural requirements for Hsp47 binding besides the known preference for third‐position Arg residues and the triple‐helical conformation.
Structure‐based phenotyping predicts HIV‐1 protease inhibitor resistance
Authors: Shenderovich Mark D. , Kagan Ron M. , Heseltine Peter N.R. , Ramnarayan Kal 
Published: February 2004

AbstractMutations in HIV‐1 drug targets lead to resistance and consequent therapeutic failure of antiretroviral drugs. Phenotypic resistance assays are time‐consuming and costly, and genotypic rules‐based interpretations may fail to predict the effects of multiple mutations. We have developed a computational procedure that rapidly evaluates changes in the binding energy of inhibitors to mutant HIV‐1 PR variants. Models of WT complexes were produced from crystal structures. Mutant complexes were built by amino acid substitutions in the WT complexes with subsequent energy minimization of the ligand and PR binding site residues. Accuracy of the models was confirmed by comparison with available crystal structures and by prediction of known resistance‐related mutations. PR variants from clinical isolates were modeled in complex with six FDA‐approved PIs, and changes in the binding energy (ΔEbind) of mutant versus WT complexes were correlated with the ratios of phenotypic 50% inhibitory concentration (IC50) values. The calculated ΔEbind of five PIs showed significant correlations (R2 = 0.7–0.8) with IC50 ratios from the Virco Antivirogram assay, and the ΔEbind of six PIs showed good correlation (R2 = 0.76–0.85) with IC50 ratios from the Virologic PhenoSense assay. ΔEbind cutoffs corresponding to a four‐fold increase in IC50 were used to define the structure‐based phenotype as susceptible, resistant, or equivocal. Blind predictions for 78 PR variants gave overall agreement of 92% (kappa = 0.756) and 86% (kappa = 0.666) with PhenoSense and Antivirogram phenotypes, respectively. The structural phenotyping predicted drug resistance of clinical HIV‐1 PR variants with an accuracy approaching that of frequently used cell‐based phenotypic assays.
The characterization of mutant Bacillus subtilis adenylosuccinate lyases corresponding to severe human adenylosuccinate lyase deficiencies
Authors: Palenchar Jennifer Brosius , Crocco Jennifer M. , Colman Roberta F. 
Published: February 2004

AbstractAdenylosuccinate lyase is a homotetramer that catalyzes two discrete reactions in the de novo synthesis of purines: the cleavage of adenylosuccinate and succinylaminoimidazole carboxamide ribotide (SAICAR). Several point mutations in the gene encoding the enzyme have been implicated in human disease. Bacillus subtilis adenylosuccinate lyase was used as a model system in which mutations were constructed corresponding to those mutations associated with severe human adenylosuccinate lyase deficiency. Site‐directed mutagenesis was utilized to construct amino acid substitutions in B. subtilis adenylosuccinate lyase; Met10, Ile123, and Thr367 were replaced by Leu, Trp, and Arg, respectively, and the altered enzymes were expressed in Escherichia coli. These purified enzymes containing amino acid substitutions were found to have substantial catalytic activity and exhibit relatively small changes in their kinetic parameters. The major deviations from the wild‐type‐like behavior were observed upon biophysical characterization. All of these enzymes with amino acid replacements are associated with marked thermal instability. I123W adenylosuccinate lyase exhibits notable changes in the circular dichroism spectra, and a native gel electrophoresis pattern indicative of some protein aggregation. T367R also exhibits alterations at the quarternary level, as reflected in native gel electrophoresis. Experimental results, combined with homology modeling, suggest that the altered enzymes are primarily structurally impaired. The enzyme instability was found to be lessened by subunit complementation with the wild‐type enzyme, under mild conditions; these studies may have implications for the in vivo behavior of adenylosuccinate lyase in heterozygous patients. Residues Met10, Ile123, and Thr367 appear to be located in regions of the enzyme important for maintaining the structural integrity required for a stable, functional enzyme.
Competitive binding of fatty acids and the fluorescent probe 1‐8‐anilinonaphthalene sulfonate to bovine β‐lactoglobulin
Authors: Collini Maddalena , D'Alfonso Laura , Molinari Henriette , Ragona Laura , Catalano Maddalena , Baldini Giancarlo 
Published: February 2004

AbstractThe use of spectroscopy in the study of fatty acids binding to bovine β‐lactoglobulin (BLG) appears to be a difficult task, as these acid compounds, assumed as the protein natural ligands, do not exhibit favorable optical response such as, for example, absorption or fluorescence. Therefore, the BLG fatty‐acid equilibrium has been tackled by exploiting the competition between fatty acids and ANS, a widely used fluorescent hydrophobic probe, whose binding sites on the protein have been characterized recently. Two lifetime decays of the ANS–BLG complex have been found; the longer one has been attributed to the internal binding site and the shorter one to the external site. At increasing fatty acids concentration, the fractional weight associated with ANS bound to the internal site drops, in agreement with a model describing the competition of the dye with fatty acids, whereas the external site occupancy appears to be unaffected by the fatty acids binding to BLG. This model is supported by docking studies. An estimate of the acid‐binding affinities for BLG has been obtained by implementing the fitting of the bound ANS intensities with a competitive binding model. A relevant dependence has been found upon the solution pH, in the range from 6 to 8, which correlates with the calyx accessibility modulated by the conformation of the EF loop. Fatty acids with longer aliphatic chains (palmitate and laurate) are found to display larger affinities for the protein and the interaction free energy nicely correlates with the number of contacts inside the protein calyx, in agreement with docking simulations.
Exploring the conformational space of membrane protein folds matching distance constraints
Authors: Faulon Jean‐Loup , Sale Ken , Young Malin 
Published: February 2004

AbstractHerein we present a computational technique for generating helix‐membrane protein folds matching a predefined set of distance constraints, such as those obtained from NMR NOE, chemical cross‐linking, dipolar EPR, and FRET experiments. The purpose of the technique is to provide initial structures for local conformational searches based on either energetic considerations or ad‐hoc scoring criteria. In order to properly screen the conformational space, the technique generates an exhaustive list of conformations within a specified root‐mean‐square deviation (RMSD) where the helices are positioned in order to match the provided distances. Our results indicate that the number of structures decreases exponentially as the number of distances increases, and increases exponentially as the errors associated with the distances increases. We also found the number of solutions to be smaller when all the distances share one helix in common, compared to the case where the distances connect helices in a daisy‐chain manner. We found that for 7 helices, at least 15 distances with errors up to 8 Å are needed to produce a number of solutions that is not too large to be processed by local search refinement procedures. Finally, without energetic considerations, our enumeration technique retrieved the transmembrane domains of Bacteriorhodopsin (PDB entry1c3w), Halorhodopsin (1e12), Rhodopsin (1f88), Aquaporin‐1 (1fqy), Glycerol uptake facilitator protein (1fx8), Sensory Rhodopsin (1jgj), and a subunit of Fumarate reductase flavoprotein (1qlaC) with Cα level RMSDs of 3.0 Å, 2.3 Å, 3.2 Å, 4.6 Å, 6.0 Å, 3.7 Å, and 4.4 Å, respectively.
The effect of dexamethasone on human mucin 1 expression and antibody‐dependent complement sensitivity in a prostate cancer cell line in vitro and in vivo
Authors: Imai Masaki , Hwang Hee‐Young , Norris James S. , Tomlinson Stephen 
Published: February 2004

SummaryDexamethasone has been shown to up‐regulate human mucin 1 (MUC1) expression in certain types of cancer cell lines in vitro, suggesting that this gluocorticoid may enhance MUC1‐based immunotherapies. Here we investigated the effect of dexamethasone on MUC1 expression in the DU145 human prostate cancer cell line in terms of antibody‐mediated complement‐dependent cell lysis. Cells treated with 1 × 10−8 m dexamethasone in vitro expressed maximal levels of MUC1 after 6 days, with an approximately 3‐fold increase over MUC1 levels on untreated cells. DU145 cells were highly resistant to lysis by anti‐MUC1 antibody and complement, and their susceptibility to antibody and complement was unaffected by dexamethasone treatment. However, dexamethasone also induced expression of the complement inhibitor decay accelerating factor (DAF) on DU145 cells. Blocking or overcoming the function of DAF resulted in enhanced complement‐dependent lysis of dexamethasone‐treated cells with anti‐MUC1 antibodies, indicating that the failure of dexamethasone to enhance the complement susceptibility of DU145 cells was caused by the up‐regulated expression of DAF. We also investigated MUC1 expression in vivo and found that MUC1 expression was significantly up‐regulated on tumour cells isolated from immune‐deficient mice that had been injected with dexamethasone. However, in contrast to in vitro data, there was no difference between the levels of DAF expressed on tumour‐derived DU145 cells isolated from either phosphate buffered saline (PBS)‐treated or dexamethasone‐treated mice, and tumour cells isolated from dexamethasone‐treated mice were more sensitive to complement‐mediated lysis. In the broad context of immunotherapy, the in vivo data support the use of dexamethasone as an adjunct treatment. Up‐regulated DAF expression would not be a favourable outcome of dexamethasone treatment in terms of complement‐dependent antibody therapy, but the in vivo data caution against extrapolation of in vitro data with regard to the modulation of complement inhibitors reported here and elsewhere.
The Child Care Arrangements of Preschool‐Age Children in Immigrant Families in the United States
Authors: Brandon Peter D. 
Published: February 2004

AbstractThis study examined the child care arrangements of children in immigrant families. Using data from the Survey of Income and Program Participation (SIPP), the study found great diversity in the child care arrangements of children according to their nativity status. Children in immigrant families, especially those in low‐income immigrant families, were found less likely to use centre‐based child care. Mexican, Asian, and other Hispanic children are also less likely to use centre‐based child care. Because quality centre‐based child care has been shown to benefit preschool‐age children and help prepare them for school, both scholastically and psychologically, less use of centre‐based child care among children in immigrant families compared to children in non‐immigrant families is a potentially troubling finding. Public policies promoting greater access to and more use of centre‐based child care, especially for low‐income immigrant families and two‐parent immigrant families, may make a significant difference to their children's long‐term adaptation, and their children's school readiness and achievement.