bluuebunny/crossref_metadata_2025 huggingface dataset:
A gene coexpression network for bovine skeletal muscle inferred from microarray data
Authors: Reverter Antonio , Hudson Nicholas J. , Wang Yonghong , Tan Siok-Hwee , Barris Wes , Byrne Keren A. , McWilliam Sean M. , Bottema Cynthia D. K. , Kister Adam , Greenwood Paul L. , Harper Gregory S. , Lehnert Sigrid A. , Dalrymple Brian P.
Published: September 2006

We present the application of large-scale multivariate mixed-model equations to the joint analysis of nine gene expression experiments in beef cattle muscle and fat tissues with a total of 147 hybridizations, and we explore 47 experimental conditions or treatments. Using a correlation-based method, we constructed a gene network for 822 genes. Modules of muscle structural proteins and enzymes, extracellular matrix, fat metabolism, and protein synthesis were clearly evident. Detailed analysis of the network identified groupings of proteins on the basis of physical association. For example, expression of three components of the z-disk, MYOZ1, TCAP, and PDLIM3, was significantly correlated. In contrast, expression of these z-disk proteins was not highly correlated with the expression of a cluster of thick (myosins) and thin (actin and tropomyosins) filament proteins or of titin, the third major filament system. However, expression of titin was itself not significantly correlated with the cluster of thick and thin filament proteins and enzymes. Correlation in expression of many fast-twitch muscle structural proteins and enzymes was observed, but slow-twitch-specific proteins were not correlated with the fast-twitch proteins or with each other. In addition, a number of significant associations between genes and transcription factors were also identified. Our results not only recapitulate the known biology of muscle but have also started to reveal some of the underlying associations between and within the structural components of skeletal muscle.
Differential brain transcriptome of β4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain?
Authors: Kedmi Merav , Orr-Urtreger Avi
Published: September 2006

Studies using mice with β4 nicotinic acetylcholine receptor (nAChR) subunit deficiency (β4−/− mice) helped reveal the roles of this subunit in bradycardiac response to vagal stimulation, nicotine-induced seizure activity and anxiety. To identify genes that might be related to β4-containing nAChRs activity, we compared the mRNA expression profiles of brains from β4−/− and wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes significantly differentiated between these two experimental groups. Of them, the two most downregulated were spastic paraplegia 21 (human) homolog ( Spg21) and 6-pyruvoyl-tetrahydropterin synthase ( Pts) genes. Since the targeted mutagenesis of the β4 nAChR subunit was done by using two mouse strains, 129SvEv and C57BL/6J, it is possible that the genes closely linked to the mutated β4 gene represent the 129SvEv allele and not the control C57BL/6J-driven allele. We examined this possibility by using public database and quantitative RT-PCR. The expression levels of Spg21 and Pts genes that, like the β4 gene, are localized on mouse chromosome 9, as well as the expression levels of other genes located on this chromosome, were dependent on the mouse background strain. The 67 differentially expressed genes that are not located on chromosome 9 were further analyzed for overrepresented functional annotations and transcription regulatory elements compared with the entire microarray. Genes encoding for proteins involved in tyrosine phosphatase activity, calcium ion binding, cell growth and/or maintenance, and chromosome organization were overrepresented. Our data enhance the understanding of the molecular interactions involved in the β4 nAChR subunit function. They also emphasize the need for careful interpretation of expression microarray studies done on genetically manipulated animals.
Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2
Authors: Jaworski Diane M. , Beem-Miller Micah , Lluri Gentian , Barrantes-Reynolds Ramiro
Published: September 2006

Nested genes are fairly common within the mammalian nervous system, yet few studies have examined whether the guest and host genes might be coordinately regulated. Tissue inhibitors of metalloproteinase (TIMPs) inhibit extracellular matrix proteolysis mediated by metzincin proteases. TIMP-2 is the only TIMP not nested within a synapsin gene. It does, however, serve as a host for differential display clone 8 (DDC8), a testis-specific gene whose expression is upregulated during spermatogenesis. Here, we demonstrate that DDC8 is not testis specific. Furthermore, DDC8 expression in nonneural and neural tissues mimics that of TIMP-2, including its upregulation in response to traumatic brain injury, suggesting a potential regulatory relationship. The most striking observation is that the TIMP-2 knockout mouse brain contains TIMP-2 mRNA encoding exons 2–5, which are downstream of DDC8, but not exon 1, which contains the signal sequence and cysteine residue required for MMP inhibition, indicating a functional knockout. That TIMP-2 transcripts in wild-type brain contain DDC8 sequence suggests alternative splicing between the two genes.
Z Ring as Executor of Bacterial Cell Division
Authors: Dajkovic Alex , Lutkenhaus Joe
Published: September 2006

It has become apparent that bacteria possess ancestors of the major eukaryotic cytoskeletal proteins. FtsZ, the ancestral homologue of tubulin, assembles into a cytoskeletal structure associated with cell division, designated the Z ring. Formation of the Z ring represents a major point of both spatial and temporal regulation of cell division. Here we discuss findings concerning the structure and the formation of the ring as well as its spatial and temporal regulation.
Intermediate Filament-Like Cytoskeleton of Caulobacter crescentus
Authors: Ausmees Nora
Published: September 2006

Eukaryotic cytoskeleton consists of three main types of filaments: actin microfilaments, microtubules and intermediate filaments (IFs). Actin and tubulin-like proteins are also found in bacteria where they perform diverse cytoskeletal functions. IFs, however, are considered to be a characteristic constituent of metazoan cells only, where they (among other functions) are involved in determination and maintenance of cell shape and cellular integrity. Surprisingly, a coiled coil-rich protein called crescentin was recently shown to play a key role in determining the complex curved and helical cell shapes of the bacterium Caulobacter crescentus, and to exhibit several characteristic properties of animal IF proteins. First, the arrangement of the coiled coil domains of crescentin closely resembles the tripartite molecular architecture of IF proteins. Second, crescentin also possesses the defining biochemical property of IF proteins to assemble into 10-nm-wide filaments in vitro without cofactors. Furthermore, crescentin forms a higher-order helical structure in vivo, which is localized asymmetrically along the concave side of the cell. In close association with the cell membrane, the crescentin structure promotes the helical growth of the cell and thereby determines a curved or a helical shape, depending on the length of the cell. The unexpected finding of an IF-like element in a bacterium raises several interesting questions concerning, for example, the molecular mechanisms whereby complex and asymmetric cell shapes are generated by different bacteria, or the functional and evolutionary relatedness of crescentin to animal IF proteins.
Cytoskeletal Cytoplasmic Filament Ribbon of Treponema: A Member of an Intermediate-Like Filament Protein Family
Authors: Izard Jacques
Published: September 2006

Development of genetic systems for many bacterial genera, including Treponema, now allow the study of structures that are specific to certain pathogens. The cytoplasmic filament ribbon of treponemes that is involved in the cell division cycle has a unique organization. Cytoplasmic bridging proteins connect the filaments, maintaining the distance between them and providing the overall ribbon-like structure. The filaments are anchored by proteins associated with the inner membrane. Each filament is composed of a unique monomer, the cytoplasmic filament protein A (CfpA), with coiled-coils secondary structures. CfpA is part of a growing family of proteins that we propose to call bacterial intermediate-like filaments (BILF).
Archaeal Flagella, Bacterial Flagella and Type IV Pili: A Comparison of Genes and Posttranslational Modifications
Authors: Ng Sandy Y.M. , Chaban Bonnie , Jarrell Ken F.
Published: September 2006

The archaeal flagellum is a unique motility organelle. While superficially similar to the bacterial flagellum, several similarities have been reported between the archaeal flagellum and the bacterial type IV pilus system. These include the multiflagellin nature of the flagellar filament, N-terminal sequence similarities between archaeal flagellins and bacterial type IV pilins, as well as the presence of homologous proteins in the two systems. Recent advances in archaeal flagella research add to the growing list of similarities. First, the preflagellin peptidase that is responsible for processing the N-terminal signal peptide in preflagellins has been identified. The preflagellin peptidase is a membrane-bound enzyme topologically similar to its counterpart in the type IV pilus system (prepilin peptidase); the two enzymes are demonstrated to utilize the same catalytic mechanism. Second, it has been suggested that the archaeal flagellum and the bacterial type IV pilus share a similar mode of assembly. While bacterial flagellins and type IV pilins can be modified with O-linked glycans, N-linked glycans have recently been reported on archaeal flagellins. This mode of glycosylation, as well as the observation that the archaeal flagellum lacks a central channel, are both consistent with the proposed assembly model. On the other hand, the failure to identify other genes involved in archaeal flagellation by homology searches likely implies a novel aspect of the archaeal flagellar system. These interesting features remain to be deciphered through continued research. Such knowledge would be invaluable to motility and protein export studies in the Archaea.
The Flagellar Cytoskeleton of the Spirochetes
Authors: Wolgemuth Charles W. , Charon Nyles W. , Goldstein Stuart F. , Goldstein Raymond E.
Published: September 2006

The recent discoveries of prokaryotic homologs of all three major eukaryotic cytoskeletal proteins (actin, tubulin, intermediate filaments) have spurred a resurgence of activity in the field of bacterial morphology. In spirochetes, however, it has long been known that the flagellar filaments act as a cytoskeletal protein structure, contributing to their shape and conferring motility on this unique phylum of bacteria. Therefore, revisiting the spirochete cytoskeleton may lead to new paradigms for exploring general features of prokaryotic morphology. This review discusses the role that the periplasmic flagella in spirochetes play in maintaining shape and producing motility. We focus on four species of spirochetes: Borrelia burgdorferi, Treponema denticola, Treponema phagedenis and Leptonema (formerly Leptospira) illini. In spirochetes, the flagella reside in the periplasmic space. Rotation of the flagella in the above species by a flagellar motor induces changes in the cell morphology that drives motility. Mutants that do not produce flagella have a markedly different shape than wild-type cells.
Is Primary Hyperaldosteronism a Risk Factor for Aortic Dissection?
Authors: Ahmed S. Hinan , Husain Nadeem M. , Khawaja Shazib N. , Massey Clara V. , Pettyjohn Frank S.
Published: September 2006

Primary hyperaldosteronism is a rare (<1%) and underdiagnosed cause of secondary hypertension. We present a case of aortic dissection in a patient with primary hyperaldosteronism. To our knowledge, there are six other reported cases of aortic dissection in patients with primary hyperaldosteronism. Our case strengthens the hypothesis that primary hyperaldosteronism is a potential independent risk factor for aortic dissection.
Influence of the Progression of Cryptococcal Meningitis on Brain Penetration and Efficacy of AmBisome in a Murine Model
Authors: Takemoto K. , Yamamoto Y. , Ueda Y.
Published: September 2006

Background: AmBisome is a small unilamellar vesicle containing amphotericin B. AmBisome is generally unable to pass through the blood-brain barrier, but the distribution of AmBisome in the brain is increased by inflammation, and in consequence, AmBisome exhibits activity against fungal meningitis. We investigated the influence of the progression of cryptococcal meningitis on the brain penetration and efficacy of AmBisome. Method: Mice were infected intracerebroventricularly with Cryptococcus neoformans 4 h or 5 days prior to a single dose treatment. Results: The brain tissue level and efficacy of AmBisome when administered 5 days after infection were greater than 4 h after infection. An immunohistochemical study showed that AmBisome-derived amphotericin B was localized at the infected site in the subarachnoid space. When AmBisome was compared with Fungizone at the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in both regimens. Conclusion: The brain penetration of AmBisome was enhanced by the progression of cryptococcal meningitis and correlated with the in vivo activity.
Fatal Liver Failure in an Adult Patient with Acute Lymphoblastic Leukemia following Treatment with L-Asparaginase
Authors: Bodmer Michael , Sulz Michael , Stadlmann Sylvia , Droll Armin , Terracciano Luigi , Krähenbühl Stephan
Published: September 2006

L-Asparaginase is commonly used in combination chemotherapy of both pediatric and adult acute lymphoblastic leukemia. The majority of adverse effects are hypersensitivity reactions, but serious liver injury may also occur. It has been shown that treatment with L-asparaginase can be associated mainly with macrovesicular hepatic steatosis which may be accompanied by alterations in lipid metabolism. So far, the mechanism for liver injury associated with L-asparaginase is not known. We report here an adult patient who developed mixed liver injury and predominantly microvesicular hepatic steatosis while being treated with L-asparaginase for acute lymphoblastic leukemia. The patient developed liver failure and died due to multiorgan failure. Both impaired liver mitochondrial function and alterations in very-low-density lipoprotein metabolism and secretion are discussed as two possible mechanisms explaining the findings observed in this patient.
B-Vitamin Status and Concentrations of Homocysteine in Austrian Omnivores, Vegetarians and Vegans
Authors: Majchrzak D. , Singer I. , Männer M. , Rust P. , Genser D. , Wagner K.-H. , Elmadfa I.
Published: September 2006

Background: A vegetarian diet is considered to promote health and longevity and reduce the risk of cardiovascular diseases and cancer. However, a vegetarian diet may be deficient in some nutrients. Exclusion of animal products in vegetarian diets may affect the status of certain B-vitamins, and further cause the rise of plasma homocysteine concentration. Objective: The nutritional status of various B-vitamins (B1, B2, B6, B12, folic acid) and the concentration of homocysteine in blood plasma of omnivores (n = 40), vegetarians (n = 36) and vegans (n = 42) in Austria was evaluated. Methods: The evaluation was done using the functional parameters erythrocyte transketolase (ETK), glutathione reductase (EGR) and glutamic oxaloacetic transaminase (EGOT) activation coefficients. Enzyme activity was measured photometrically. The quantity of vitamins B1, B2 and B6 in urine and the concentrations of vitamin B6 and homocysteine in plasma were determined by HPLC methods with fluorescence detection. Plasma concentration of vitamin B12 and folic acid were measured with radioimmunoassay. Results: Most of the subjects showed a satisfying vitamin B1 status. Vegans presented a significantly lower mean plasma vitamin B12 concentration than omnivores and vegetarians and deficiency in 2.4% of the volunteers but the highest mean value of plasma folate among the investigated groups. A deficient status of folate was found in 18% of omnivores and in approximately 10% of vegans and vegetarians. The status of riboflavin is considered to be deficient in about 10% of omnivores and vegetarians and in over 30% of vegans. According to the activation coefficient of GOT, approximately one third of all subjects showed vitamin B6 deficiency. Elevated homocysteine concentration in plasma was observed in 66% of the vegans and about 45–50% of the omnivores and vegetarians. Vegan subjects had significantly higher mean plasma homocysteine levels than omnivores. Conclusion: Thiamin and folate need not be a problem in a well-planned vegan diet. Vitamins B12 and B2 may need attention in the strict vegan diet, especially regarding elevated homocysteine levels in plasma. Pyridoxine status appeared to be independent of the diet.
Sensory and Affective Aspects of Dyspnea Contribute Differentially to the Borg Scale’s Measurement of Dyspnea
Authors: von Leupoldt Andreas , Ambruzsova Rita , Nordmeyer Simone , Jeske Nina , Dahme Bernhard
Published: September 2006

Background:Recent research has shown that distinct dimensions in the perception of dyspnea can be differentiated; however, most studies to date have only used a global rating scale for the measurement of this sensation. Objectives: This study examined the different influence of sensory and affective aspects of perceived dyspnea on the commonly used Borg scale, which measures the global perception of dyspnea. Methods: Dyspnea was induced in 16 healthy volunteers (mean age 26.2 ± 6.3 years) by breathing through an inspiratory resistive load (3.57 kPa/l/s) in two experimental conditions (attention and distraction). After each of the two conditions the experienced intensity (i.e., sensory dimension) and unpleasantness (i.e., affective dimension) of dyspnea were rated on separate visual analog scales (VAS), followed by a global rating of dyspnea on the Borg scale. Hierarchical multiple linear regression models were calculated to analyze the predictive validity of VAS ratings of intensity and unpleasantness on the Borg scale ratings. Results: When subjects attended to their breathing, only VAS intensity scores showed a significant influence on Borg scale ratings (p < 0.05). In contrast, only the VAS unpleasantness scores showed a significant influence on Borg scale ratings (p < 0.05) when subjects were distracted. Conclusions: These findings show that sensory and affective aspects of perceived dyspnea differentially influence the global measure of dyspnea as determined by the Borg scale. A differentiation between these aspects in future studies through the use of separate rating scales could yield more detailed information on the perception and report of dyspnea.
Prevention of home-related injuries of preschoolers: Safety measures taken by mothers
Authors: Al-Khameesa Nedaa A
Published: September 2006

Objective The aim of this study was to find out the extent of safety measures taken by mothers to prevent serious injuries to their pre-school children in the home, and the factors that influence mothers' behaviour in taking these safety measures.

Design A self-completion questionnaire based on a Five Level Likert Scale was used in the study.

Setting Respondents were mothers with pre-school children througout the state of Kuwait.

Methods 550 questionnaires were personally distributed to, and colected from, a random sampling of college students and their families, employees in selected ministries and companies, and to attendees at selected gatherings.

Results 510 fully completed questionnaires were returned. Mothers were most safety conscious in the bathroom and in preventing children from falling, least aware of hazards in the living room, and had modeate use of safety measures in respect of hazards in the child's bedroom and prevention of burns and poisoning. Correlation of these results with demographic data showed the mother's educational level, number of children, age, marital status, residential status and occupational status all influenced the degree of use of safety measures.

Conclusion Emphasis should be given to the several safety measures found to be not used by a significant number of mothers, and each such measure should be advocated separately. Mothers with lesser education, student mothers, mothers with larger families, and widowed or divorced mothers should be especially targeted.
Barriers to uptake of eye care services by the Indian population living in Ealing, west London
Authors: Patel Daksha , Baker Helen , Murdoch Ian
Published: September 2006

Background Despite a relatively high prevalence of eye disease, the Indian population in London does not fully utilize the available eye care services. This study in Ealing, London was aimed at determining the reasons for poor utilization of eye care services.

Methods Qualitative research methods were used. These included: focus group discussions with community members and religious leaders; semi-structured interviews with general practitioners and Indian patients attending the eye unit for the first time at Ealing hospital, and non-participatory observation methods.

Results Attitudinal barriers showing visual health is not a priority and the elderly are resigned to a ‘fate’ of poor vision in old age. Difficulties in the patient-doctor relationship at the primary care level that cause delays in gaining access to specialist care. Dissatisfaction at hospital level due to long waiting lists and poor communication with specialists and staff.

Although the community does not perceive language as a major barrier, the majority of patients receiving health care in the hospital system still need interpreters often resulting in dissatisfaction and misconceptions.

Conclusion The social attitudes towards visual health issues, along with the perceived difficulties with their general practitioners result in delays in seeking help for their visual impairment. These are the principal barriers that would have to be addressed if uptake of services is to be improved.
Pharmacokinetics of Tipifarnib After Oral and Intravenous Administration in Subjects With Advanced Cancer
Authors: Zhang Steven , Zannikos Peter , Awada Ahmad , Piccart‐Gebhart Martine , Dirix Luc Y. , Fumoleau Pierre , Verhaeghe Tom , Francois Marc , De Porre Peter
Published: September 2006

The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice‐daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects were randomly assigned to receive 3 consecutive 4‐day regimens of tipifarnib with different treatment sequences: a 100‐mg 2‐hour intravenous infusion, 200‐mg oral administration twice daily, and a 200‐mg/d continuous intravenous infusion. The systemic exposure to tipifarnib was comparable among these 3 regimens. The plasma concentration‐time profile of 2‐hour intravenous infusion more closely resembled the oral administration than did the continuous infusion. Glucuronidation is a metabolic pathway for tipifarnib with concentrations of the glucuronide conjugate greatly exceeding the parent compound after oral and intravenous administration. Analysis of plasma metabolites indicated that tipifarnib also undergoes dealkylation and loss of the imidazole group.
Population Pharmacokinetic Analysis and Dosing Regimen Optimization of Meropenem in Adult Patients
Authors: Li Chonghua , Kuti Joseph L. , Nightingale Charles H. , Nicolau David P.
Published: September 2006

The objectives of this study were to develop a meropenem population pharmacokinetic model using patient data and use it to explore alternative dosage regimens that could optimize the currently used dosing regimen to achieve higher likelihood of pharmacodynamic exposure against pathogenic bacteria. We gathered concentration data from 79 patients (ages 18–93 years) who received meropenem 0.5, 1, or 2 g over 0.5‐ or 3‐hour infusion every 8 hours. Meropenem population pharmacokinetic analysis was performed using the NONMEM program. A 2‐compartment model fit the data best. Creatinine clearance, age, and body weight were the most significant covariates to affect meropenem pharmacokinetics. Monte Carlo simulation was applied to mimic the concentration‐time profiles while 1 g meropenem was administrated via infusion over 0.5, 1, 2, and 3 hours. The 3‐hour prolonged infusion improved the likelihood of obtaining both bacteriostatic and bactericidal exposures most notably at the current susceptibility breakpoints.
Investigation of a Potential Food Effect on the Pharmacokinetics of Roflumilast, an Oral, Once‐Daily Phosphodiesterase 4 Inhibitor, in Healthy Subjects
Authors: Hauns Bernhard , Hermann Robert , Hünnemeyer Andreas , Herzog Rolf , Hauschke Dieter , Zech Karl , Bethke Thomas D.
Published: September 2006

This open, randomized, single‐dose crossover study investigated effects of a high‐fat meal on the pharmacokinetics of roflumilast and its major active N‐oxide metabolite. Twelve healthy subjects received oral roflumilast 500 μg (2 × 250 μg) after overnight fasting and after breakfast. Blood was sampled up to 54 hours for pharmacokinetic profiling of roflumilast and N‐oxide. Geometric mean ratios (fed/fasted) for point estimates (PE) and 90% confidence intervals (CI) were calculated for AUC0‐last, AUC0‐∞, and Cmaxof both compounds. After the meal, roflumilast Cmax(PE, 0.59; 90% CI, 0.49‐0.70) was modestly reduced; N‐oxide Cmax(PE, 0.95; 90% CI, 0.90‐1.01) was unchanged. Roflumilast tmaxwas delayed in fed state (2.0 ± 0.4 hours) versus fasted state (1.0 ± 0.2 hours); N‐oxide tmaxwas unaltered. No significant food effect on roflumilast AUC0‐last(PE, 1.04; 90% CI, 0.90‐1.21), AUC0‐∞(PE, 1.12; 90% CI, 1.00–1.25), and respective N‐oxide AUCs (PE, 0.91; 90% CI, 0.79‐1.04; PE, 0.99; 90% CI, 0.92‐1.06) occurred. Because roflumilast N‐oxide is the major contributor to roflumilast's overall pharmacologic effects, these findings suggest that roflumilast can be taken with or without food.
Effect of Exenatide on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Asian Men
Authors: Soon Danny , Kothare Prajakti A. , Linnebjerg Helle , Park Soomin , Yuen Eunice , Mace Kenneth F. , Wise Stephen D.
Published: September 2006

Exenatide, a treatment for type 2 diabetes, slows gastric emptying as part of its pharmacologic action and may alter the absorption of concomitant oral drugs. This open‐label, 2‐period, fixed‐sequence study evaluated the influence of exenatide coadministration on the pharmacokinetics and pharmacodynamics of warfarin, a narrow therapeutic index drug, in healthy men (N = 16). A single, 25‐mg oral dose of warfarin, with a standardized breakfast, was administered alone in period 1 and concomitantly with 10 μg exenatide subcutaneous twice daily in period 2. Exenatide did not produce significant changes in R‐ or S‐warfarin pharmacokinetics. Although there were minor reductions in warfarin anticoagulant effect, the ratios of geometric means for the area under the international normalized ratio (INR)–time curve from dosing until the time of the last measurable INR value or maximum‐observed INR response being 0.94 (0.93‐0.96) and 0.88 (0.84‐0.92), respectively, the magnitude and direction of these changes do not suggest a safety concern from this interaction.
Pharmacokinetic Evaluation and Safety Profile of a 15‐Minute Versus 30‐Second Infusion of Palonosetron in Healthy Subjects
Authors: Shah Ajit , DeGroot Timothy , Apseloff Glen
Published: September 2006

Palonosetron is a potent, selective 5‐HT3 receptor antagonist effective in the prevention of acute and delayed chemotherapy‐induced nausea and vomiting. In practice, 5‐HT3 receptor antagonists, including palonosetron, are often coadministered with dexamethasone over approximately 15 minutes, although the approval of palonosetron was based on administration as a 30‐second infusion. This open‐label, randomized, 2‐way crossover trial compared the pharmacokinetics and safety of palonosetron 0.25 mg administered as a 15‐minute 50‐mL intravenous infusion with a 30‐second 5‐mL infusion. Aside from an anticipated 40% decrease in maximum plasma concentration after a 15‐minute infusion, the pharmacokinetics of palonosetron (including area under the plasma concentration‐time curve [AUC], plasma elimination half‐life, total body clearance, and apparent volume of distribution at steady state) were similar for both treatments. Both treatments were well tolerated, with no significant changes in vital signs or electrocardiograms. Palonosetron infused over 15 minutes is well tolerated, with an AUC0‐∞ equivalent to a 30‐second infusion.
Gatifloxacin Pharmacokinetics in Healthy Men and Women
Authors: Zhang Xin , Overholser Brian R. , Kays Michael B. , Sowinski Kevin M.
Published: September 2006

The sex‐based pharmacokinetics of gatifloxacin were investigated. Healthy subjects (6 men, 6 women) received a single oral dose of gatifloxacin 400 mg. Blood and urine samples were collected, and gatifloxacin concentrations were determined by high‐performance liquid chromatography. Pharmacokinetic parameters were estimated by fitting appropriate models to the serum concentration‐time data using ADAPT II. Linear regression analysis was used to determine the influence of sex and weight on the oral clearance (CLs/F) and apparent steady‐state volume of distribution (Vss/F) of gatifloxacin. Women had a significantly smaller Vss/F compared to men (93.5 ± 21.3 L vs 128.8 ± 16.2 L, P = .009); however, there was no significant difference when normalized for total body weight (TBW) or lean body weight (LBW). Neither CLs/F nor peak serum concentration (Cmax) was significantly different between sexes, although Cmax was 25% higher in women (P = .06). Regression analyses revealed that TBW (R2 = .63) and LBW (R2 = .65) were strong predictors of Vss/F. Given the smaller Vss/F, women may have slightly higher maximum concentrations, but these differences are unlikely to have clinical significance.
Disposition and Metabolite Kinetics of Oral L‐carnitine in Humans
Authors: Bain Marcus A. , Milne Robert W. , Evans Allan M.
Published: September 2006

The pharmacokinetics of L‐carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L‐carnitine across an 8‐hour dose interval increased significantly (P <.05) from a baseline of 54.2 ± 9.3 μM to 80.5 ± 12.5 μM following the 0.5‐g dose; there was no further increase at higher doses. There was a significant increase (P <.001) in the renal clearance of L‐carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L‐carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine‐N‐oxide from baseline was evident only for the 2‐g dose of L‐carnitine (from 34.5 ± 2.0 to 149 ± 145 μM), and its renal clearance decreased with increasing dose (P <.05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine‐N‐oxide. In conclusion, the pharmacokinetics of oral L‐carnitine display nonlinearity above a dose of 0.5 g 3 times a day.
Inside Elliott’s empire
Authors: Wells Dominic
Published: September 2006

A former editor of Time Out charts the magazine's growth from a London listings title to an international brand and comments: "[Proprietor] Tony Elliott has always been cautious about expansion, more perhaps even than he realises. He was once incensed by a journalist who compared him unfavourably with his contemporary Richard Branson: now there was a man, said the article, who could diversify his brand portfolio - going from records to clothing, soft drinks, insurance, trains and an airline. 'What on earth do they mean?' Tony fumed. 'I've diversified. I've got the Time Out city guides, Time Out Eating Guide, the Time Out Film Guide...' One-track minded he may be, but he's hitched quite a number of carriages on to the original train in the last 40 years. After launching a sister magazine in New York, which defied all media pundits to become a commercial triumph, he has licensed the Time Out name and know-how to listings guides in 13 cities and counting."
We know better than the courts
Authors: Meyer Christopher
Published: September 2006

The chairman of the Press Complaints Commission argues vigorously against legislation on privacy and intrusion. He writes: "Statutory regulation is objectionable in principle and incompatible with a properly functioning democracy. (I would be ready to bet that one of these days the State will get out of the business of regulating content in television and radio; and that an expanded system of self-regulation will cover all forms of content delivery.) There are also practical problems. When I became the Prime Minister's press secretary in 1994, the first thing I found in my in-tray was a draft White Paper proposing a Privacy Bill. After innumerable redrafts, it foundered on the intractable problem of defining where private space met public interest; and on the political objection to passing a law from which only those who could afford the legal bills would benefit. None of these objections has gone away."
The French Foreign Legion
Authors: Cooper Nicola J.
Published: September 2006

An analysis of the ways in which national or ethnic identities are transformed and a new common identity is forged amongst legionnaires intersects with key factors which have been perennially important to the discussion of transnational communities: the very creation of that sense of community, the importance of a shared history and heritage, the transmission of a cultural memory. Different versions of the legionnaire ‘myth’ in popular culture show how the image of the Legion readily adapts to culturally and historically specific milieux, thereby translating across national borders. Thus although it might be argued that the Legion disseminates a certain idea of Frenchness across borders, it also serves as a useful vehicle for other nations’ own mythologies.
Against Integration or Against Using Evolutionary Theory to Homogenize Psychology?
Authors: Goertzen Jason R.
Published: September 2006

This paper comments on an article by Derksen, who argues that the theory of evolution cannot unify the social sciences in general and psychology in particular. Derksen also elevates his ‘against integration’ argument to an in-principle level whereby he rejects integration as a solution to the problem of fragmentation. Where Derksen limits his arguments to evolutionary theory, they are welcome; however, where he elevates his arguments to an in-principle level, they become unmindful of a vast history on fragmentation and integration/unification. Derksen also implicitly defines integration as seamless homogeneity, which is only one definition of integration/unification used in the literature. Finally, his alternatives to integration are found to be lacking in detailed explanation and critical reflection.
Family Figures in 20th-Century British ‘Psy’ Discourses
Authors: Hollway Wendy
Published: September 2006

This article takes the three figures—child, mother-child couple and father—and charts their discursive movements over the course of the 20th century in Britain, concentrating particularly on the changes happening around the time of the 1939-45 war. Over time, there is a significant shift from the individual child to the mother-child relation and the importance of fathers for children’s self development appears and disappears as a theme. A rigid construction of stages unevenly gives way to an idea of phase less amenable to a normative discourse. At any given time, there is considerable diversity within ‘psy’ discourses, and I focus particularly on the differences between and among psychological and psychoanalytic discourses. Certain expressions of psychoanalysis have, in my view, been more successful in theorizing subjectivity as it develops over time within the relations of the family in a way which exceeds or transcends the ‘psy’ complex’s subjectifications and yet does not reduce personhood to an asocial essence. By locating its ontology within the practices and epistemology of psychoanalysis, I consider the conditions for this relative freedom.
Global Capitalism and the Critique of Real Time
Authors: Hope Wayne
Published: September 2006

Digital technologies globally interlink finance, production, consumption, mass communication, and cyberculture. The processes of interlinkage generate the sense that time is accelerating towards instantaneity. Promoters and critical observers of such developments have created a proliferating discourse of ‘real time’. This key phrase and its associated terminology covers a diversity of referent spaces (e.g. cyberculture, financial flows, supply-chain management, on-line selling, live media events). In the context of global capitalism, discursive constructions of ‘real time’ are interrelated with new temporal constructions of systemic power. The nature of this interrelationship is obscured by the ideological features of ‘real time’ terminology. Here, this argument will be developed with references to popular business literature and (supposedly) critical academic writings. I conclude with a set of preliminary requirements for an effective critique of ‘real time’.
Time for Housework and Time for ‘Oshigoto’
Authors: Yuasa Masae
Published: September 2006

This article investigates the time use and consciousness of a group of housewives working for Maple, a Japanese network business organizing 200,000 housewives all over Japan. The three years of fieldwork show that the invisible time organization of the housewives has been a vital obstacle to their business success. However, the article argues their time organization does not derive from static gendered time consciousness but it is rather produced and reproduced at the local level, through ideologies, discourses and practices.
Sleeping through Class to Success
Authors: Steger Brigitte
Published: September 2006

Japanese high-school students often study until late into the night and sacrifice their sleep in order to pass entrance and other exams. On the other hand, they often take a nap in the (late) afternoon, and daytime napping or inemuri is widely tolerated. This article asks what cultural and social sense it makes to keep students up for studying, when they cannot concentrate on what is being said in class. It examines notions of time and diligence based on the ethnographic findings and analyses sleep, especially inemuri, from sociological perspective.
Japan's ‘Socially Withdrawn Youths’ and Time Constraints in Japanese Society
Authors: Kaneko Sachiko
Published: September 2006

This article discusses how time is conceptualized among hikikomori, or Japan’s so called ‘socially withdrawn youth’, through the narratives of hikikomori keikensha (those who experienced hikikomori) and also examines time and space management in hikikomorisupport context based on ethnographic data. Hikikomoriis an act of retreat from time and space constraints in society. Hikikomorisupport groups provide a place for them to be without feeling such time constraints, but this is not considered sufficient to get hikikomoriback into society. Hikikomori, which challenges the usual coordinates of time and space, may be understood as a kind of reaction to time pressures and role performances in Japanese society.
Passive Vibration Control of Beams Subjected to Random Excitations with Peaked PSD
Authors: Younesian D. , Esmailzadeh E. , Sedaghati R.
Published: September 2006

Vibration suppression in beams subjected to random excitations with peaked Power Spectral Densities (PSDs) is studied in this paper. An optimal Tuned Mass Damper (TMD) system is used to suppress the undesirable vibration. The Timoshenko beam theory is applied to the beam model and the governing equations of motion are solved using the Galerkin method. Using the Sequential Quadratic Programming (SQP) method, the problem is solved to obtain the optimum values of the design variables (i.e. frequency ratio and the damping ratio) of the TMD system. Subsequently, a parametric study is carried out and the effects of the input parameters, such as the mass ratio, structural damping ratio, and the peak frequency of the random excitation on the design variables were investigated. The robustness of the optimal control system is also studied. Based on the PSD of the random excitation and using a Monte Carlo simulation algorithm, a set of numerical data for the excitation force is generated in the time domain and the effectiveness of the designed TMD system is investigated.
Control of Wind-induced Nonlinear Oscillations in Suspension Bridges using Multiple Semi-active Tuned Mass Dampers
Authors: Abdel-Rohman Mohamed , John Mariam Joseph
Published: September 2006

The effectiveness of using Multiple Tuned Mass Dampers (MTMD) to increase the critical wind speed of a flexible long span suspension bridge subjected to wind loading is studied. The mean wind direction is assumed to be perpendicular to the plane of the suspended cable. The along-wind response and across-wind response of the suspended cables and the bridge deck response due to wind are studied, and it is shown that using a single passive or semi-active tuned mass damper (STMD) with a large mass at the mid-span of the bridge raises the critical wind speed of the suspension bridge. As the installation of a single large passive or semi-active tuned mass damper is problematic, we investigate the effectiveness of using multiple tuned mass dampers (MTMD) with small masses located at various positions along the bridge deck. In order to further increase the critical wind speed, the passive MTMD are supplemented by velocity feedback active control forces. The effects of the dampers’ locations, the mass ratio and the damping ratio on the critical wind speed are also investigated.
Refiguring the European Union’s Historical Dimension
Authors: Chalmers Adam
Published: September 2006

The European Union requires a stronger approach to social solidarity than has been offered in existing theory. Perhaps the exigency of this claim is nowhere more evident than in the recent failed referendums in France and the Netherlands. In both cases the narrow legal-economic sense of the EU won out over what was hoped to be an emerging European public sphere, indeed a shared sense of European identity rooted in history. This article asks what type of ‘history’ this identity requires. Approaching this problem from a theoretical perspective, I will outline why and how such a ‘history’ must accord with the existing limits set by post-and/or transnationalism itself. Second, I will question how well various attempts at writing such a ‘history’ have already managed in terms of these limits. Lastly, drawing on the current work of sociologist Ulrich Beck, I will put forward a theoretical alternative to the existing models.
Activation of αIIbβ3 is a sufficient but also an imperative prerequisite for activation of α2β1 on platelets
Authors: Van de Walle Gerlinde R. , Schoolmeester Anne , Iserbyt Brecht F. , Cosemans Judith M. E. M. , Heemskerk Johan W. M. , Hoylaerts Marc F. , Nurden Alan , Vanhoorelbeke Karen , Deckmyn Hans
Published: September 2006

Platelet integrins α2β1 and αIIbβ3 play critical roles in platelet adhesion and thrombus formation after vascular injury. On resting platelets, both integrins are in a low-affinity state. However, agonist stimulation results in conformational changes that enable ligand binding that can be detected with conformation dependent monoclonal antibodies (mAbs). By using such conformation-dependent mAbs, we could demonstrate that activation of integrin αIIbβ3 is not only sufficient, but also a prerequisite for α2β1 activation. Compared with platelets in plasma, stimulation of washed platelets resulted in only a minor activation of α2β1, as detected with the activation-sensitive mAb IAC-1. Addition of fibrinogen to stimulated washed platelets greatly potentiated activation of this integrin. Also, treatment of αIIbβ3 with the ligand-mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful α2β1 activation, even in the absence of overall platelet activation, involving tyrosine kinase activity but no protein kinase C activation. The absolute necessity of αIIbβ3 for proper α2β1 activation on platelets was demonstrated by using the αIIbβ3 antagonist aggrastat, which was able to completely abolish α2β1 activation, both under static and flow conditions. In addition, analogous experiments with Glanzmann platelets lacking αIIbβ3 confirmed the indispensability of αIIbβ3 for α2β1 activation.
Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group
Authors: Bhatia Smita , Krailo Mark D. , Chen Zhengjia , Burden Laura , Askin Frederic B. , Dickman Paul S. , Grier Holcombe E. , Link Michael P. , Meyers Paul A. , Perlman Elizabeth J. , Rausen Aaron R. , Robison Leslie L. , Vietti Teresa J. , Miser James S.
Published: September 2006

This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.