bluuebunny/crossref_metadata_2025 huggingface dataset:
Meiotic abnormalities in infertile males
Authors: Egozcue J. , Sarrate Z. , Codina-Pascual M. , Egozcue S. , Oliver-Bonet M. , Blanco J. , Navarro J. , Benet J. , Vidal F.
Published: September 2005

Meiotic anomalies, as reviewed here, are synaptic chromosome abnormalities, limited to germ cells that cannot be detected through the study of the karyotype. Although the importance of synaptic errors has been underestimated for many years, their presence is related to many cases of human male infertility. Synaptic anomalies can be studied by immunostaining of synaptonemal complexes (SCs), but in this case their frequency is probably underestimated due to the phenomenon of synaptic adjustment. They can also be studied in classic meiotic preparations, which, from a clinical point of view, is still the best approach, especially if multiplex fluorescence in situ hybridization is at hand to solve difficult cases. Sperm chromosome FISH studies also provide indirect evidence of their presence. Synaptic anomalies can affect the rate of recombination of all bivalents, produce achiasmate small univalents, partially achiasmate medium-sized or large bivalents, or affect all bivalents in the cell. The frequency is variable, interindividually and intraindividually. The baseline incidence of synaptic anomalies is 6–8%, which may be increased to 17.6% in males with a severe oligozoospermia, and to 27% in normozoospermic males with one or more previous IVF failures. The clinical consequences are the production of abnormal spermatozoa that will produce a higher number of chromosomally abnormal embryos. The indications for a meiotic study in testicular biopsy are provided.
Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: oligozoospermia
Authors: Miharu N.
Published: September 2005

Recently, intracytoplasmic sperm injection (ICSI) has been extremely successful for the treatment of male infertility. However, transmission of cytogenetic defects to offspring is a great concern. There are two types of cytogenetic problems in patients seeking ICSI; one is the transmission of genetic defects from patients with constitutional chromosomal abnormalities and the second is the generation of de novo defects in infertile men. Generally about 5.1% of infertile men have chromosomal abnormalities. Among such infertile men, men with severe spermatogenesis defects, including oligozoospermia and azoospermia, are subjects for ICSI. Therefore it is very important to obtain cytogenetic information in these infertile patients. Furthermore, oligozoospermic men with a normal somatic karyotype also have increased frequencies of sperm chromosome abnormalities. Oligozoospermia is usually associated with other sperm alterations, for example oligoasthenozoospermia, oligoteratozoospemia and oligoasthenoteratozoospermia. In this review, the relationship between sperm concentration and sperm aneuploidy frequencies has been analyzed. The inverse correlation between the frequency of sperm aneuploidy and concentration has been reported in extensive studies. Especially in severe oligozoospermia, a significantly higher frequency of sex chromosome aneuploidy has been observed and this has been corroborated in recent clinical outcome data of ICSI.
Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: asthenozoospermia
Authors: Rives N.M.D.
Published: September 2005

The aim of aneuploidy evaluation in spermatozoa from patients presenting spermatogenesis defects is to identify a relationship between meiotic errors and quantitative or qualitative alterations of spermatogenesis. During the past ten years, the use of fluorescence in situ hybridization (FISH) has permitted the determination of the frequency of numerical chromosome aberrations in different clinical situations. It has been established that infertile males with reduced sperm count and a normal constitutional karyotype have a significantly high risk of aneuploidy in their spermatozoa particularly regarding sex chromosomes. Concerning sperm motility, the data are more controversial. However, patients of severe asthenozoospermia induced by specific morphological deformities involving sperm flagella have a significantly high risk of producing aneuploid spermatozoa.
Effect of lifestyle exposures on sperm aneuploidy
Authors: Robbins W.A. , Elashoff D.A. , Xun L. , Jia J. , Li N. , Wu G. , Wei F.
Published: September 2005

Lifestyle exposures including cigarette smoke, alcohol, and caffeine have all been studied in relationship to male reproductive health. Over the years the focus has primarily been on semen quality and/or fertility. More recently, literature evaluating direct adverse effects of lifestyle exposures on sperm chromosomes and chromatin has grown due to concern that induced damage could be transmitted to offspring causing transgenerational health effects. In this paper we present a new analysis that summarizes published studies of smoking effects on sperm chromosome number and demonstrates a statistically significant increase in sperm disomy among smokers compared to nonsmokers (P < 0.001). In addition, new data on the effect of alcohol intake on sperm chromosome number are presented showing a rate ratio of 1.38 (95% CI 1.2, 1.6) for XY frequency in sperm of alcohol drinkers compared to nondrinkers.
Mouse genetic models for aneuploidy induction in germ cells
Authors: Eichenlaub-Ritter U.
Published: September 2005

Rodents have been successfully used as models to identify risks of chemical exposures or age to aneuploidy induction in germ cells, which may be transmitted to the progeny. For this administration in vivo as well as exposures to in vitro maturing germ cells have been useful. Genetic models involving mice with structural chromosomal rearrangements and transgenic animals have the potential to model conditions predisposing to aneuploidy in one or both sexes, and in this way to identify potential targets for aneugens and gender-effects. The review provides an overview of mouse genetic models for aneuploidy induction in mammalian germ cells and discusses perspectives for combining genetic with experimental approaches in aneuploidy research.
Airway Responses to the Inhalation of Cotton Dust and Cotton Bract Extracts
Authors: Schachter E.Neil , Zuskin Eugenija , Buck Marion , Witek Theodore J. , Godbold James , Roy Noah , Castranova Vincent , Whitmer Michael , Siegel Paul D. , Bluhm Elisabeth C.
Published: September 2005

Background: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis. Objectives: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects. Methods: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg). Results: There were 18 responders to CBE and 17 responders to CDE.The average maximal falls in MEF40%(P) were 70 ± 4.9 and 70 ± 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF40%(P) by 40% was identical for CBE and CDE (1.3 µg/ml). Conclusions: We conclude that CBE and CDE exert similar physiologic effects.
Habitual Loud Snoring. A Study of Prevalence and Associations in 850 Middle-Aged French Males
Authors: Teculescu Dan , Benamghar Lahoucine , Hannhart Bernard , Michaely Jean-Pierre
Published: September 2005

Background: Most studies on habitual snoring have focused on its prevalence. However, from the clinical point of view, the intensity of snoring is of upmost importance, as it suggests the existence of sleep apnoeas. Objectives: The aim of the study was to assess the prevalence of loud snoring using a standard questionnaire and to evaluate the anthropometric and sleep characteristic differences between loud and light snorers in a sample of middle-aged males. Methods: The subjects were middle-aged active male employees. They completed a structured sleep questionnaire and had standard anthropometric measurements. Subjects reporting habitual snoring (≧3 nights/week) were further classified as loud or light snorers. Results: Of the 850 male subjects volunteering, 149 (17.5%) were habitual loud snorers. Loud snorers were older and had a greater waist-to-hip ratio as compared with light snorers. In univariate analysis, loud snoring was associated with gasping/snorting during sleep, breathing stops during sleep, waking up too early, excessive daytime sleepiness and falling asleep while watching TV. Logistic regression identified four independent associates of loud snoring: gasping during sleep, excessive daytime sleepiness, falling asleep watching TV and age. Conclusions: Loud snoring is present in a significant proportion of middle-aged men and is associated with central obesity and age. It disturbs sleep and elicits significant daytime sleepiness. Its association with breathing pauses (univariate) and its independent association with gasping during sleep suggests that loud snoring could be considered a clinical correlate of obstructive sleep apnoeas.
Alterations in T-Lymphocyte Subsets in the Airways of Asthmatic Patients with Active Hepatitis C Virus Infection
Authors: Kanazawa Hiroshi , Yoshikawa Junichi
Published: September 2005

Background: The interaction between hepatitis C virus (HCV) infection and certain pulmonary disorders is of considerable interest. We have previously found that active HCV infection in asthmatic patients is associated with impaired responses to inhaled corticosteroid therapy. Objectives: To examine differences in T-lymphocyte subsets in asthmatic airways with or without HCV infection. Methods: 12 HCV-negative and 29-HCV positive asthmatics were included in this study. All HCV-positive asthmatics received interferon (IFN) therapy (11 IFN responders and 18 IFN non-responders). T-lymphocyte subsets in induced sputum were analyzed before and 1 year after IFN therapy. Results: Before IFN therapy, percentages of lymphocytes and CD8+ T lymphocytes in induced sputum were higher in HCV-positive asthmatics than in HCV-negative asthmatics. After IFN therapy, there was no significant change in percentages of lymphocytes and T-lymphocyte subsets in IFN non-responders. However, percentage of lymphocytes and CD8+ T lymphocytes in IFN responders significantly decreased, while CD4+ T lymphocytes increased. Therefore, the CD4/CD8 ratio significantly increased following IFN therapy in IFN responders. In IFN responders, forced expiratory volume in 1 s (FEV1) after salbutamol administration significantly increased following IFN therapy, while it did not change in non-responders. In addition, in IFN responders, the change in the CD4/CD8 ratio after IFN therapy was significantly correlated with the increase in FEV1 after salbutamol administration. Conclusions: The number of CD8+ T lymphocytes increases in the airways of asthmatic patients with active HCV infection, and this may be associated with airway dysfunction in these patients.
Exclusion of Four Candidate Genes, KHDRBS2, PTP4A1, KIAA1411 and OGFRL1, as Causative of Autosomal Recessive Retinitis Pigmentosa
Authors: Abd El-Aziz Mai M. , Patel Reshma J. , El-Ashry Mohamed F. , Barragan Isabel , Marcos Irene , Borrego Salud , Antiñolo Guillermo , Bhattacharya Shomi S.
Published: September 2005

To identify the disease gene in 6 Spanish families with autosomal recessive retinitis pigmentosa linked to the RP25 locus, mutation screening of 4 candidate genes, KHDRBS2, PTP4A1, KIAA1411 and OGFRL1, was undertaken based on their expression or functional relevance to the retina. Twenty-six single nucleotide polymorphisms were identified, of which 14 were novel. Even though no pathological mutations were detected, these genes however remain as good candidates for other retinal degenerations mapping to the same chromosomal region.
Donepezil in Vascular Dementia: Combined Analysis of Two Large-Scale Clinical Trials
Authors: Román Gustavo C. , Wilkinson David G. , Doody Rachelle S. , Black Sandra E. , Salloway Stephen P. , Schindler Rachel J.
Published: September 2005

Background and Objective: There are currently no drugs approved to treat vascular dementia (VaD).The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients. Methods: Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS[-]cog), Mini-Mental State Examination (MMSE)], global function [Clinician’s Interview- Based Impression of Change plus (CIBIC[-]plus), Clinical Dementia Rating – Sum of the Boxes (CDR[-]SB)] and function [Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS[-]IADL)].Results:Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p< 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p< 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events. Conclusions: This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD.
Connexin 46 and Connexin 50 in Selenite Cataract
Authors: Fleschner C.R.
Published: September 2005

The purpose of this work was to determine if the lens gap junction proteins connexin 46 (Cx46) and connexin 50 (Cx50) were altered with the development of selenite-induced cataract. Cataracts were induced in young Sprague-Dawley rats with a single subcutaneous injection of sodium selenite; age-matched uninjected rats served as controls. Membrane fractions were isolated from homogenates of cortex and nucleus of normal and cataractous lenses by differential and discontinuous sucrose gradient centrifugation. Aliquots of urea-insoluble protein from membrane fractions were analyzed by quantitative densitometry of Western blots probed with antibodies to Cx46 and Cx50. A significant decrease in the more slowly migrating Cx46-reactive band, which represents phosphorylated Cx46, was found in the major membrane fraction of the cortex of cataractous lenses. There was no significant difference in the amounts of either Cx46 or Cx50 associated with selenite cataract in any of the membrane fractions examined. These results suggest that alteration of gap junction function (as evidenced by the change in phosphorylation of Cx46) may be associated with the development of the selenite cataract, but that neither Cx46 nor Cx50 is subject to the well-characterized proteolysis associated with the selenite cataract model.
Rhabdomyolysis Caused by Tocolysis with Oral Ritodrine Hydrochloride in a Pregnant Patient with Myotonic Dystrophy
Authors: Nasu Kaei , Sugano Terumasa , Yoshimatsu Jun , Narahara Hisashi
Published: September 2005

Drug-induced rhabdomyolysis during pregnancy is extremely rare. We report here a rare case of ritodrine-hydrochloride-induced rhabdomyolysis in a pregnant patient with myotonic dystrophy. A 32-year-old primigravida was admitted because of premature labor at 31 weeks of gestation. She had been diagnosed as having myotonic dystrophy by electromyographic investigations and abnormal serum creatinine phosphokinase (CPK) levels. Tocolysis was initiated with oral ritodrine hydrochloride (15 mg/day) alone. There was a prompt response to the ritodrine hydrochloride. Three days after administration began, serum CPK levels had become markedly elevated to 10,897 mg/dl and myoglobinuria was detected (1,800 ng/dl), suggesting the presence of rhabdomyolysis. There was no evidence of worsening of the myotonic symptoms. Tocolysis was stopped immediately, and the laboratory data improved gradually. At 37 weeks of gestation, she spontaneously delivered a healthy male baby. Rhabdomyolysis has been recognized as a complication of tocolytic therapy with ritodrine hydrochloride. Therefore, β-adrenergic agents should be used with great care, especially for patients with myotonic dystrophy, because of these agents’ tendency to aggravate or precipitate myotonia and to induce rhabdomyolysis.
Effects of Hypoxia on Megakaryocyte Progenitors Obtained from the Umbilical Cord Blood of Term and Preterm Neonates
Authors: Saxonhouse Matthew A. , Rimsza Lisa M , Stevens Gary , Jouei Nazanin , Christensen Robert D. , Sola Martha C.
Published: September 2005

Background: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment. Objective: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34pos cells, either cultured alone or in conjunction with CD34neg light density mononuclear cells (LDMCs). Methods: CD34pos cells and CD34neg LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34pos cells were obtained from healthy adults. CD34pos cells were then cultured alone or co-cultured with CD34neg LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10–12 days. Mk colonies were then quantified following immunohistochemical staining. Results: Pure CD34pos cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O2 concentrations. Conclusions: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34pos cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.
Alzheimer’s Disease: Role of Size and Location of White Matter Changes in Determining Cognitive Deficits
Authors: Bracco L. , Piccini C. , Moretti M. , Mascalchi M. , Sforza A. , Nacmias B. , Cellini E. , Bagnoli S. , Sorbi S.
Published: September 2005

This study investigated the contribution that white matter changes (WMCs) make to clinical and cognitive features in Alzheimer’s disease (AD), independently ofpossible confounders such as cortical atrophy and the apolipoprotein E genotype as well as their relationship to vascular risk factors. We semiquantitatively assessed the degree and location of WMCs (global, periventricular and deep white matter), lacunes and global atrophy on brain MRI scans of 86 AD cases, extensively evaluated from a clinical and neuropsychological point of view. Multivariate logistic and linear regression analysis showed that age was the only significant predictor of all WMC measures and revealed a significant association of periventricular WMCs with performance on executive function tasks as well as of deep WMCs with history of mood depression. Our results underline the significance of WMC location over size in the occurrence of specific cognitive deficits in AD.
Antihypertensive Effects of Drospirenone With 17β-Estradiol, a Novel Hormone Treatment in Postmenopausal Women With Stage 1 Hypertension
Authors: White William B. , Pitt Bertram , Preston Richard A. , Hanes Vladimir
Published: September 2005

Background—

Drospirenone (DRSP) is a novel progestin with antimineralocorticoid activity that has been developed for hormone therapy in combination with 17β-estradiol (E2) in postmenopausal women. In prior studies with DRSP in postmenopausal women that were focused on relief of menopausal symptoms, DRSP/E2 yielded significant reductions in blood pressure (BP).

Methods and Results—

The effects of 3 mg DRSP/1 mg E2 on clinic and 24-hour ambulatory BP as well as potassium homeostasis were evaluated in postmenopausal women with stage 1 hypertension (systolic, 140 to 159 and/or diastolic, 90 to 99 mm Hg) in a 12-week, multicenter, double-blind, randomized, placebo-controlled study. Clinic BPs were measured at baseline and at 2, 4, 6, 8, and 12 weeks of therapy, whereas potassium was measured at 2, 6, and 12 weeks of therapy. Ambulatory BP was performed in a substudy at baseline and at the end of the trial. In the intention-to-treat population of 213 women, the clinic BP was reduced significantly on DRSP/E2 (clinic BP, −14.1/−7.9 for DRSP/E2 versus −7.1/−4.3 mm Hg for placebo,
P
<0.0001). In the subgroup of 43 women with ambulatory BP monitoring, the 24-hour BP fell by −8.5/−4.2 mm Hg versus −1.8/−1.6 mm Hg on placebo (
P
=0.002/0.07). There were no significant changes from baseline in potassium levels or in the incidence of hyperkalemia (≥5.5 meq/L) on DRSP/E2 compared with placebo.

Conclusions—

Combination therapy with DRSP/E2 significantly lowered both clinic and 24-hour systolic BP in postmenopausal women with stage 1 systolic hypertension. This characteristic may lead to benefit for cardiovascular risk reduction in this population.
Electrophysiological Characteristics of Septal Hypertrophy in Patients With Hypertrophic Obstructive Cardiomyopathy and Moderate to Severe Symptoms
Authors: Schumacher Burghard , Gietzen Frank H. , Neuser Hans , Schümmelfeder Joachim , Schneider Michael , Kerber Sebastian , Schimpf Rainer , Wolpert Christian , Borggrefe Martin
Published: September 2005

Background—

In hypertrophic obstructive cardiomyopathy, regional hypertrophy, myocardial replacement scarring, expanded interstitial fibrosis, and myocardial disarray can be found. The electrophysiological consequences of this substrate have not yet been investigated. Thus, the aim of this study was to assess the local electrophysiological characteristics of regional left ventricular (LV) septal hypertrophy.

Methods and Results—

In 9 patients with hypertrophic obstructive cardiomyopathy, electroanatomic voltage mapping of the LV was performed during sinus rhythm to determine the regional voltage amplitude. In addition, the morphology of the regional bipolar endocardial electrogram was assessed. During multisite LV stimulation, the stimulus-to-V intervals in both septal hypertrophy and the lateral LV myocardium were determined. Bipolar electroanatomic voltage mapping revealed a significant reduction in regional voltage amplitude in septal hypertrophic areas compared with lateral LV areas without evidence of hypertrophy (0.41±0.24 versus 13.5±1.85 mV;
P
<0,001). Local bipolar electrogram analysis demonstrated fractionated and prolonged endocardial potentials in septal hypertrophic areas (with split potentials present in 6 patients) that were not revealed at lateral myocardial sites (110.1±24.6 versus 80.1±6.6 ms;
P
=0.005). The stimulus-to-V interval was significantly longer (62.9±10.3 versus 24.1±9.1 ms;
P
=0.005) in septal hypertrophic areas compared with the lateral LV.

Conclusions—

In LV regions with extensive hypertrophy, a marked reduction of bipolar voltage amplitude can be found, as well as local conduction delay and conduction block. This result is consistent with the findings of regional myocardial scarring and may contribute to the increased incidence of ventricular tachyarrhythmias in patients with hypertrophic obstructive cardiomyopathy.
CD40 Ligand–Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo
Authors: Davis Bradley , Zou Ming-Hui
Published: September 2005

Background—

Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand, CD40L, but the mechanisms and the mediators by which CD40L contributes to atherosclerosis are poorly defined. Here, we show how CD40L increases vascular inflammation and thrombosis via tyrosine nitration and inhibition of prostacyclin synthase (PGIS), an enzyme with antithrombotic, antiproliferative, and dilatory functions in the normal vasculature.

Methods and Results—

Exposure of cultured human aortic endothelial cells to clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently increased the production of superoxide (O
2
·−
), decreased nitric oxide (NO) bioactivity, and increased PGIS nitration. Furthermore, inhibition of CD40 expression by small interfering RNA blocked the effects of CD40L on O
2
·−
, NO bioactivity, and PGIS nitration, which indicates a specific effect of CD40L. In addition, either depletion of mitochondria (ρ
0
cells, ie, mitochondria-depleted cells, to prevent mitochondrial O
2
·−
) or adenoviral overexpression of superoxide dismutase, as well as inhibition of NO synthase, abolished the CD40L-enhanced PGIS nitration, which implies that the mitochondria might be the source of O
2
·−
and thus peroxynitrite (ONOO
−
). Furthermore, SQ29548, a thromboxane A
2
/prostaglandin H
2
receptor antagonist, significantly reduced CD40L-enhanced expression of intercellular adhesion molecule-1. Finally, administration of CD40L resulted in PGIS inhibition and nitration in the aortas of C57BL6 mice but less in mice overexpressing human superoxide dismutase, which suggests that ONOO
−
might be required for CD40L-enhanced PGIS nitration in vivo.

Conclusions—

We conclude that CD40L might contribute to the initiation and progression of atherosclerosis by increasing O
2
·−
- and ONOO
−
-dependent PGIS nitration and thromboxane A
2
/prostaglandin H
2
receptor stimulation.
Postconditioning the Human Heart
Authors: Staat Patrick , Rioufol Gilles , Piot Christophe , Cottin Yves , Cung Thien Tri , L’Huillier Isabelle , Aupetit Jean-François , Bonnefoy Eric , Finet Gérard , André-Fouët Xavier , Ovize Michel
Published: September 2005

Background—

In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction.

Methods and Results—

Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events occurred in the postconditioning group. Determinants of infarct size, including ischemia time, size of the area at risk, and collateral flow, were comparable between the 2 groups. Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group, averaging 208 984±26 576 compared with 326 095±48 779 (arbitrary units) in control subjects, ie, a 36% reduction in infarct size. Blush grade, a marker of myocardial reperfusion, was significantly increased in postconditioned compared with control subjects: 2.44±0.17 versus 1.95±0.27, respectively (
P
<0.05).

Conclusions—

This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infarction.
Simple Risk Stratification at Admission to Identify Patients With Reduced Mortality From Primary Angioplasty
Authors: Thune Jens Jakob , Hoefsten Dan Eik , Lindholm Matias Greve , Mortensen Leif Spange , Andersen Henning Rud , Nielsen Torsten Toftegaard , Kober Lars , Kelbaek Henning
Published: September 2005

Background—

Randomized trials comparing fibrinolysis with primary angioplasty for acute ST-elevation myocardial infarction have demonstrated a beneficial effect of primary angioplasty on the combined end point of death, reinfarction, and disabling stroke but not on all-cause death. Identifying a patient group with reduced mortality from an invasive strategy would be important for early triage. The Thrombolysis in Myocardial Infarction (TIMI) risk score is a simple validated integer score that makes it possible to identify high-risk patients on admission to hospital. We hypothesized that a high-risk group might have a reduced mortality with an invasive strategy.

Methods and Results—

We classified 1527 patients from the Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) trial with information for all variables necessary for calculating the TIMI risk score as low risk (TIMI risk score, 0 to 4) or high risk (TIMI risk score ≥5) and investigated the effect of primary angioplasty versus fibrinolysis on mortality and morbidity in the 2 groups. Follow-up was 3 years. We classified 1134 patients as low risk and 393 as high risk. There was a significant interaction between risk status and effect of primary angioplasty (
P
=0.008). In the low-risk group, there was no difference in mortality (primary angioplasty, 8.0%; fibrinolysis, 5.6%;
P
=0.11); in the high-risk group, there was a significant reduction in mortality with primary angioplasty (25.3% versus 36.2%;
P
=0.02).

Conclusions—

Risk stratification at admission based on the TIMI risk score identifies a group of high-risk patients who have a significantly reduced mortality with an invasive strategy of primary angioplasty.
The complementarity of audit and judicial review: the ‘homes for votes’ scandal in the UK
Authors: Drewry Gavin
Published: September 2005

The mechanisms of public accountability can take many different forms, and those who hold others to account must themselves be accountable. A recent case of serious electoral malpractice in a UK local authority illustrates some important points about mechanisms of accountability and redress — in particular the potential complementarity between the inquisitorial role of an auditor, and the essentially adversarial nature of the judicial process. It also illustrates how the courts can be used to hold auditors (who are, themselves, important instruments of accountability) to account for their actions. Unlike an auditor, courts have limited scope to conduct in-depth investigations of the issues that arise in litigation, so it is tempting to consider the possibility of providing an investigative facility for particularly complex cases. However, as the case discussed here illustrates, this would involve substantial additional costs, as well as delays in the final resolution of disputes, at a time when the courts are under increasing pressure to streamline their procedures and become more cost-effective.
CAPAM Symposium on Networked Government: Building public trust through public–private partnerships
Authors: Brewer Brian , Hayllar Mark R.
Published: September 2005

Collaborative working through public–private partnerships, though not new, has become more common. Strong partnerships are built and sustained by norms of reliability consistent with the high levels of systemic trust that the principles of good governance encourage. This article examines two public–private partnerships in Hong Kong in which government actions have severely undermined the trust necessary for the public–private partnership model to work effectively. In the first case, the trust established through a long-standing government/civil society partnership in the delivery of school-based education has been dissipated by acrimonious public wrangling over the autonomy of the service providers. The second case focuses on a large-scale infrastructure project to build an arts hub on redeveloped land. Policy inconsistencies by the Hong Kong government, together with deep suspicions about the extent to which large, well-connected businesses have influenced the project’s development, have seriously undermined the trust of arts community stakeholders and the general public.
Trust and governance practices among local leaders
Authors: de Vries Michiel S.
Published: September 2005

This article investigates patterns of generalized trust among local political and administrative leaders. It explains the differences therein and studies the impact of such trust on the inclination to involve people in policy-making processes. The research is based on a survey among approximately 16,000 local administrators and politicians in 665 communities in 18 countries. The findings are analyzed using a multi-level model. It is found that generalized trust among local policy-makers, as a form of low-level risk, can be explained by the judgment about past experiences with public participation, the judgment of the abilities of the constituency and the scope of problems in the community. Regarding the impact of trust on the propensity to involve people in the policy-making process, significant differences are found between old, new and newest democracies. In the old democracies there is hardly a relation between the tendency to seek the support of citizens on the one hand and generalized trust on the other hand. The severity of social problems has in these countries a positive effect on involving citizens. In the new and especially the newest democracies, the relation between trust and support-seeking behavior is significantly stronger. When problems become less urgent in those countries and the local policy-maker does show generalized trust,(s)he is significantly more inclined than his/her colleagues to seek the support of the people. This implies that there might exist a paradox, namely that in order to enhance practices of good governance, claiming these are more effective, one already needs a society in which policy-making is relatively effective and that has adequate problem-solving capacity.
Management Development
Authors: Gray Colin , Mabey Christopher
Published: September 2005

Driven by concerns over Europe's competitive position in global markets, the role of leadership and management in boosting efficiency, productivity and innovation in European firms has moved up the public policy agenda. However, small firm participation in formal management development has been significantly lower than that for large organizations. The main focus of this article is on management training and development as a strategic activity. Seven partners in Britain, Denmark, Norway, France, Germany, Spain and Romania, took part in the LEONARDO programme's European Management Development project. Each surveyed structured samples of 100 firms, interviewing at least one senior manager and one line manager in each firm. This article contrasts the 191 small firms (20–100 employees) with 201 large firms (500 or more employees). The main contrasts in management development practices were partly due to size effects but also partly due to key differences in strategic approaches to management development.
Environmental Management Systems in Small and Medium Businesses
Authors: McKeiver Catherine , Gadenne David
Published: September 2005

This study examines the various external, moderating and internal factors that may influence the implementation of an environmental management system within a limited sample of small and medium-sized enterprises (SMEs). Both formal and informal environmental management systems were considered within this study. The results indicate that age, customers, and employees' concerns were significantly associated with the informal level of implementation of an environmental management system. Furthermore, education, legislation, and awareness were found to be significantly associated with the formal level of implementation of an environmental management system. Although the strategies identified as being used in practice indicate that the majority of businesses are following a resistant strategy, there is hope in the prospect that SMEs will continue to listen to their relevant publics and continue to improve their environmental management systems. Implications and suggestions for further research are also stated.
Understanding Small Business Taxpayers
Authors: Ahmed Eliza , Braithwaite Valerie
Published: September 2005

This study investigates how the self-employed define themselves and their businesses in relation to taxation issues, and whether there is evidence that this segment engages with taxation in ways that are different from other segments of the population. Data are collected from a random sample of 2040 Australians. Four domains are chosen for comparison: perceived deterrence for non-compliance, tax morale, perceived fairness, and work practice. As evident in the discriminant function analysis, the self-employed are distinguished by not receiving an annual tax refund, perceiving themselves as paying less than their fair share of tax, having less tax competence and independence, perceiving greater power in the tax office to elicit compliance, favouring small government and minimum government interference, and opposing tax expenditure for redistributive programmes such as health, welfare and education. Findings are discussed in a regulatory context.
From Pi to Pie
Authors: Hoey Brian A.
Published: September 2005

Research introduced here examines the impact of social and structural transitions during the past three decades on middle-class working families in the United States. Through the telling narrative of an especially iconic case of urban-to-rural migration and career change, this article explores the meaning of relocation away from metropolitan areas and corporate careers to growing ex-urban, small-town communities. The author interprets this life-style migration as a manner of personally negotiating tension between experience of material demands in pursuit of a livelihood within the flexible New Economy and prevailing cultural conventions for the good life that shape the moral narratives that define individual character. Drawing on two years of ethnographic research involving interview and observation of recent migrants to Northern Michigan, this article contributes to our understanding of noneconomic migration and its part in the changing moral meanings of work in postindustrial America.
The Role of Play in the Formation and Maintenance of Cultural Identity
Authors: Levinson Martin P.
Published: September 2005

Drawing on data from a three-and-a-half-year ethnographic study of Gypsy life in England, this article explores the orientations of Gypsy children toward play and the way in which play operates to affirm a separate identity and enforce boundaries. The apparently uncontrolled, and at times destructive, behavior of Gypsy children in a social/play context has been perceived by some observers as a barrier to educational progress. To illustrate and explore some of these themes, a number of vignettes are provided, through which patterns of play behavior are considered in different contexts, structured and unstructured, in home and school settings. Throughout the discussion, there is a search for sociocultural interpretations of play patterns that appear to differ from norms of the mainstream group, and an attempt is made to consider ways in which such patterns might fill a vacuum created by the erosion of traditional identity markers.
Impressions of Grandmother
Authors: Rambo Carol
Published: September 2005

Through the use of a layered account format, the author sketches, through a juxtapositioning of vignettes and impressions, an autoethnographic portrait of her grandmother. Derrida’s concepts such as the “mystic writing pad,” “differance,” and “sous rature” serve as frames through which to gaze at the emergent nature of identity formation across time. Various aspects of the author’s grandmother’s character, positive, negative, and shades of gray, are illustrated through descriptions of drawing. Through reflexivity, she will show how some of the impressions her grandmother left with her manifest in her. Derrida’s concepts, the layered account format, and drawing, serve individually as viewfinders that offer snapshots of her grandmother and her but, taken together, build up traces and impressions that merge and blend into an illustration of identity as a process and thus an autoethnographic portrait.
Mechanical properties of friction welded joint between Ti–6Al–4V alloy and Al–Mg alloy (AA5052)
Authors: Kimura M. , Nakamura S. , Kusaka M. , Seo K. , Fuji A.
Published: September 2005

The present paper describes the mechanical properties of a friction welded joint between Ti–6Al–4V alloy and Al–Mg alloy (AA5052). The Ti–6Al–4V/AA5052–H112 joint, made at a friction speed of 27.5 rev s−1, friction pressure of 30 MPa, friction time of 3.0 s, and forge pressure of 60 MPa, had 100% joint efficiency and fractured in the AA5052–H112 base metal. The Ti–6Al–4V/AA5052–H34 joint, made under the same friction welding conditions, did not achieve 100% joint efficiency and it fractured in the AA5052–H34 base metal because the AA5052–H34 base metal had softened under friction heating. The joints made at low friction speed or using short friction time showed fracture at the welded interface because a sufficient quantity of heat for welding could not be produced. However, the joints made at high friction speed or using long friction time were also fractured at the welded interface: in this instance, the welded interface also had an intermetallic compound layer consisting of Ti2Mg3Al18. The Ti–6Al–4V/AA5052–H34 joint made at a friction speed of 27.5 rev s−1 with friction pressure of 150 MPa, friction time of 0.5 s, and forge pressure of 275 MPa had 100% joint efficiency and fractured in the AA5052–H34 base metal, although the AA5052–H34 side softened slightly. In conclusion, the Ti–6Al–4V/AA5052–H112 joint and Ti–6Al–4V/AA5052–H34 joint had 100% joint efficiency and fractured in the AA5052 base metal when made under the friction welding conditions described above.
The roles of Bcl-xL in modulating apoptosis during development of Xenopus laevis
Authors: Johnston Jillian , Chan Robert , Calderon-Segura Maria , McFarlane Sarah , Browder Leon W
Published: September 2005

Background

Apoptosis is a common and essential aspect of development. It is particularly prevalent in the central nervous system and during remodelling processes such as formation of the digits and in amphibian metamorphosis. Apoptosis, which is dependent upon a balance between pro- and anti-apoptotic factors, also enables the embryo to rid itself of cells damaged by gamma irradiation. In this study, the roles of the anti-apoptotic factor Bcl-xL in protecting cells from apoptosis were examined in Xenopus laevis embryos using transgenesis to overexpress the XR11 gene, which encodes Bcl-xL. The effects on developmental, thyroid hormone-induced and γ-radiation-induced apoptosis in embryos were examined in these transgenic animals.

Results

Apoptosis was abrogated in XR11 transgenic embryos. However, the transgene did not prevent the apoptotic response of tadpoles to thyroid hormone during metamorphosis. Post-metamorphic XR11 frogs were reared to sexual maturity, thus allowing us to produce second-generation embryos and enabling us to distinguish between the maternal and zygotic contributions of Bcl-xL to the γ-radiation apoptotic response. Wild-type embryos irradiated before the mid-blastula transition (MBT) underwent normal cell division until reaching the MBT, after which they underwent massive, catastrophic apoptosis. Over-expression of Bcl-xL derived from XR11 females, but not males, provided partial protection from apoptosis. Maternal expression of XR11 was also sufficient to abrogate apoptosis triggered by post-MBT γ-radiation. Tolerance to post-MBT γ-radiation from zygotically-derived XR11 was acquired gradually after the MBT in spite of abundant XR11 protein synthesis.

Conclusion

Our data suggest that Bcl-xL is an effective counterbalance to proapoptotic factors during embryonic development but has no apparent effect on the thyroid hormone-induced apoptosis that occurs during metamorphosis. Furthermore, post-MBT apoptosis triggered by irradiation before the MBT could only be restrained by maternal expression of Bcl-x

L
. Although maternal expression of XR11 was sufficient to abrogate apoptosis triggered by post-MBT γ-radiation, radiation tolerance from zygotically-derived XR11 was acquired gradually, indicating that synthesis of XR11 protein is not sufficient to prevent apoptosis. Thus, repression of radiation-induced apoptosis by overexpression of Bcl-xL during embryonic development depends upon the timing of its expression and post-translational events that enable the protein to become effective.
Synthesis of Cubic Ia3d-like Mesostructured Silica at Low Temperature Using an Oligomeric Nonionic Surfactant
Authors: Lim SungHyun , Yoshitake Hideaki , Tatsumi Takashi
Published: September 2005

A mesoporous silica having the cubic structure similar to MCM-48 has been synthesized at low temperature using Brij 56 as surfactant in acidic media free of additives as evidenced by showing (211) and (220) reflection peaks in the XRD patterns and the same TEM images as MCM-48.
Highly Effective Synthesis of Cyclohexanone Oxime over a Novel Titanosilicate Ti-MWW
Authors: Song Fen , Liu Yueming , Wu Haihong , He Mingyuan , Wu Peng , Tatsumi Takashi
Published: September 2005

Liquid-phase ammoximation of cyclohexanone proceeds extremely efficiently, selectively, and stablely over a novel titanosilicate Ti-MWW in a clean solvent of water, which would lead to a potential process more environmentally benign for synthesizing cyclohexanone oxime.
Sodium Trifluoroacetate: an Efficient Difluorocarbene Precursor for Alkenes
Authors: Chang Ying , Cai Chun
Published: September 2005

A novel and efficient difluorocarbene precursor was achieved. In a convenient procedure, a variety of alkenes could be gem-difluorocyclopropanated with sodium trifluoroacetate to give the corresponding products in moderate to high yields, using azobisisobutyronitrile (AIBN) as the catalyst.
Synthesis and Characterization of Host (Nanodimensional Pores of Zeolite-Y)–Guest [Unsaturated 16-Membered Octaaza–macrocycle Manganese(II), Cobalt(II), Nickel(II), Copper(II), and Zinc(II) Complexes] Nanocomposite Materials
Authors: Salavati-Niasari Masoud
Published: September 2005

Nanodimensional pores of zeolite-Y (host) encapsulated Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of unsaturated 16-membered octaaza–macrocycle (guest), 3,4,7,8,11,12,15,16-octamethyl-1,2,5,6,9,10,13,14-octaaza[16]annulene “Me8[16]aneN8”, were synthesized and characterized.