bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Cerebrovascular Symptoms and Microembolic Signals With the Stratified Gray-Scale Median Analysis and Color Mapping of the Carotid Plaque
Authors: Sztajzel Roman , Momjian-Mayor Isabelle , Comelli Mario , Momjian Shahan
Published: February 2006

Background and Purpose—

To determine whether a stratified gray-scale median (GSM) analysis of the carotid plaque combined with color mapping correlated better with the presence of neurological symptoms and microembolic signals (MES) than a whole plaque measurement.

Methods—

A total of 131 patients presenting 167 carotid stenoses between 30% and 99% were analyzed by ultrasound. Emboli detection was performed by transcranial Doppler. For each plaque, the GSM values at depth 0 mm (surface) and at one third (30) and one half (50) of the plaque thickness were compared with the values obtained for the whole plaque. The plaque pixels were mapped into 3 colors: red, yellow and green, depending on their GSM value.

Results—

Mean GSM values were lower among symptomatic plaques, but a statistically significant difference between values of the whole plaque and those of the surface was obtained only for MES+ stenoses (
P
<0.01). In a proportional odds logistic regression model based on 4 subgroups with an increasing clinical risk (MES−/symptoms−; MES−/symptoms+; MES+/symptoms−; +; MES+/symptoms+), low mean GSM values and the predominant red color at the surface were independent factors associated with the presence of symptoms or MES (
P
<0.0005). Furthermore, compared with a whole plaque measurement, analysis of the surface values predicted systematically with a greater sensitivity and specificity (receiver operating characteristic curves) each one of these 4 subgroups.

Conclusions—

Low mean GSM values and predominance of the red color at the surface correlated with most of the symptomatic or MES+ stenoses. This combined approach should be further investigated in a longitudinal study.
Wolfgang Mommsen, 1930–2004
Authors: Stern Fritz
Published: February 2006

One of our preeminent historians, Wolfgang Mommsen, died on August 11, 2004, at the age of seventy-three. Death came while he was swimming off Usedom, in the Baltic Sea. To speak of him as “ours” is to say at once that he was a treasured international presence for all of us, that he fully embodied the new transnational character of historical studies. His prodigious work and ebullient temper enriched the lives of his students, colleagues, and friends.
Rescuing Children and Policing Families: Adoption Policy in Weimar and Nazi Germany
Authors: Mouton Michelle
Published: February 2006

Whenthe First World War ended, Germany experienced an unprecedented period of political revolution, economic turmoil, and social upheaval. Among the myriad problems facing the nation was one concern that cut across party lines and prompted attention at both the national and local levels. Lawmakers, doctors, clergy, and ordinary Germans across the political spectrum agreed that the breakdown of the family had weakened the nation, contributed to military defeat, worsened economic misery, and exacerbated societal conflict. High divorce and illegitimacy rates together with an alarmingly low birth rate created a picture of families in crisis. The belief was widespread that only by creating policies that strengthened families would Germany stand a chance of regaining its historical strength. Because both Weimar and National Socialist policymakers saw the family as essential to rejuvenating the battered nation, the interwar era witnessed a wide variety of family-directed policies. Social welfare, unemployment benefits, health insurance, and maternity benefits were just the beginning of a series of programs designed to strengthen Germany and support families. While state programs targeted many different groups within society, children stood out as especially worthy recipients. Policymakers in both the Weimar and National Socialist eras recognized that children, the most vulnerable members of society and the nation's future, required special attention.
Nazifying Christmas: Political Culture and Popular Celebration in the Third Reich
Authors: Perry Joe
Published: February 2006

Radicalregimes revolutionize their holidays. Like the French Jacobins and the Russian Bolsheviks, who designed festival cultures intended to create revolutionary subjects, National Socialists manipulated popular celebration to build a “racially pure” fascist society. Christmas, long considered the “most German” of German holidays, was a compelling if challenging vehicle for the constitution of National Socialist identity. The remade “people's Christmas” (Volksweihnachten) celebrated the arrival of a savior, embodied in the twinned forms of the Führer and the Son of God, who promised national resurrection rooted in the primeval Germanic forest and the “blood and soil” of the authenticVolk. Reinvented domestic rituals, brought to life by the “German mother” in the family home, embedded this revamped Christmas myth in intimate moments of domestic celebration. An examination of “people's Christmas” across this spectrum of public and private celebration offers a revealing case study of National Socialist political culture in action. It illuminates the ways Germans became Nazis through participation both in official festivities and the practices of everyday life and underscores the complexity of the relationship between popular celebration, political culture, and identity production in the “Third Reich.”
Romanticism, Spectacle, and a Critique of Wilhelmine Consumer Capitalism
Authors: Hamlin David
Published: February 2006

Many elements were woven into this rather sneering assertion by Ferdinand Avenarius, founder and editor of the leading cultural journal of Wilhelmine Germany,Der Kunstwart. Toys, by then thoroughly commercialized consumer goods, had “true value.” By extension, consumer goods could have value. Unfortunately for Avenarius, that value stands in “inverse ratio to its dazzle.” Dazzle did not simply obscure or even eliminate value, but rather maintained a complicated link. “Value” was the mirror image of “dazzle,” varying in equal and opposite proportion. That “inverse ratio” was also connected to the power that dazzle had over “weak minds.” The values and assumptions that informed and united Avenarius' broadside represent the subject of this essay. For Avenarius was not piecing together ideas at random, nor were they applicable to toys alone. Rather, this outburst was but one example of a persistent effort by German cultural elites to assess the problems as well as the possibilities of an increasingly commercial, even consumerist society. In that effort, Avenarius and others would mobilize the Romantic suspicion of vision and reemphasize the central importance of creativity and autonomous self-expression in the construction of genuine subjectivity. In this way, important elements of the Romantic tradition worked to authorize, even promote, certain types of consumer items while stigmatizing others, suggesting a nuanced and historically specific response to the challenges of modern consumerism.
A Feminized Church? The Campaign for Women's Suffrage in Alsace-Lorraine's Protestant Churches, 1907–1914
Authors: Steinhoff Anthony J.
Published: February 2006

By 1850, a major shift in how Europeans participated in the Christian religion was well underway. On Sundays, most members of a church's or chapel's congregation were women. Women received communion more assiduously than their male counterparts. Catholic religious congregations for women were founded and joined at rates well above those for men. In Protestant lands, women became deaconesses. From Italy to Scotland, women contributed greatly to churches' social and charitable missions through their active involvement in voluntary associations and parish committees. Moreover, mothers now had the primary obligation to nourish religious sentiments in the home. Even the representation of angels had changed, the powerful, free masculine figure replaced by one who was restrained, domesticated, and feminine.
Why does Origen Refer to the Trinitarian Authorship of Scripture in Book 4 of Peri Archon?
Authors:   Martens
Published: February 2006

There are only two passages in Peri Archon where Origen refers to the trinitarian authorship of Scripture. Both of these passages have, however, elicited either little or misleading commentary from the literature. In this article I will show how these two trinitarian expressions play a decisive role in Origen's larger polemic against his main exegetical adversaries, the Jews and the Gnostics. At stake is the identification of the authorship of Scripture and, thus also, its resulting message.
Domestic opposition to Byzantium's alliance with Saladin: Niketas Choniates and his Epiphany oration of 1190
Authors: Angelov Dimiter G.
Published: February 2006

The alliance between Isaac II Angelas and Saladin at the time of the Third Crusade has received much attention from Western and Islamic contemporaries, yet the Byzantine sources are oddly silent. This article teases out a negative reaction in Byzantium to the alliance, a reaction found in an oration delivered by Niketas Choniates on 6 January 1190. The article concludes that Choniates opposed the alliance and tactfully urged Isaac II to turn his attention towards redeeming Jerusalem, then under Saladin's control. The conclusion is set within the larger framework set by other scholars, such as Magdalino, Angold, and Hamilton, who see the Holy Land as an important factor in Byzantine policy before 1176.
Surface modification of bentonites. III. Sol-gel transitions of Na-montmorillonite in the presence of trimethylammonium- end-capped poly(ethylene oxides)
Authors: Lagaly G. , Ziesmer S.
Published: February 2006

The colloidal state (sol, flocs, gels) of Na-montmorillonite dispersions (from bentonite from Bavaria, Germany) was adjusted by the addition of poly(ethylene oxides) with terminal trimethylammonium groups. The colloidal state of the dispersions changed with the molar mass of these end-capped poly(ethylene oxides). The sol-gel diagrams (up to 4.5% (w/w) montmorillonite) in the presence of TMA-PEO 1500 and TMA-PEO 4000 (up to 40 g/l) were characterized by large fields of gel whereas TMA-PEO 20000 and TMA-PEO 35000 caused peptization by steric stabilization. Even dispersions with the highest montmorillonite content (4.5%) were peptized by >0.2 g/l TMA-PEO 35000. The critical coagulation concentration of NaCl was increased by the polymer addition, but the increase was modest (from 8-12 mmol/l to 50 mmol/l). The changes of the colloidal state, the flow behaviour and the salt coagulation reveal the sensitive interplay between stabilization mechanisms (electrostatic, steric) and destabilization effects (bridging, charge compensation, depletion flocculation).
Grafted organic derivatives of kaolinite: I. Synthesis, chemical and rheological characterization
Authors: Gardolinski J. E. F. C. , Lagaly G.
Published: February 2006

Several new interlayer-grafted derivatives of kaolinite were synthesized by esterification of inner-surface hydroxyl groups with alkanols, diols and glycol mono-ethers starting with the dimethyl sulphoxide intercalate. The derivatives were characterized by X-ray powder diffractometry, thermal analysis, Fourier transform infrared spectroscopy and transmission electron microscopy. The grafted molecules are arranged in monolayers between the kaolinite layers, with typical basal spacings of ~11.3 Å. Rheological studies of aqueous dispersions of the modified kaolinites revealed an exponential increase of the yield value and apparent viscosity with increasing alkyl chain length of the grafted molecules.
Grafted organic derivatives of kaolinite: II. Intercalation of primary n-alkylamines and delamination
Authors: Gardolinski J. E. F. C. , Lagaly G.
Published: February 2006

Kaolinite was intercalated with n-hexylamine, n-octadecylamine and n-docosanamine, using methanol-kaolinite as the precursor. The intercalation compound with n-docosanamine presented the largest basal spacing for a kaolinite derivative thus far reported (64.2 Å). Five grafted derivatives of kaolinite were directly intercalated with n-hexyl- and n-octadecylamine. During intercalation, the grafted molecules rearrange from parallel to perpendicular orientation to the kaolinite surface, in order to maximize the interaction with the amine and minimize the interlayer expansion needed. The octadecylamine intercalation compounds were delaminated in toluene, accompanied by the deintercalation of the amine molecules. Thin kaolinite particles rolled into a halloysite-like morphology, but forming much smaller tubes, some of which possibly consist of single kaolinite layers. The delamination was more efficient with the grafted kaolinites than with raw kaolinite.
KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium
Authors: Dekker Rob J. , Boon Reinier A. , Rondaij Mariska G. , Kragt Astrid , Volger Oscar L. , Elderkamp Yvonne W. , Meijers Joost C. M. , Voorberg Jan , Pannekoek Hans , Horrevoets Anton J. G.
Published: February 2006

The flow-responsive transcription factor KLF2 is acquiring a leading role in the regulation of endothelial cell gene expression. A genome-wide microarray expression profiling is described employing lentivirus-mediated, 7-day overexpression of human KLF2 at levels observed under prolonged flow. KLF2 is not involved in lineage typing, as 42 endothelial-specific markers were unaffected. Rather, KLF2 generates a gene transcription profile (> 1000 genes) affecting key functional pathways such as cell migration, vasomotor function, inflammation, and hemostasis and induces a morphology change typical for shear exposure including stress fiber formation. Protein levels for thrombomodulin, endothelial nitric oxide synthase, and plasminogen activator inhibitor type-1 are altered to atheroprotective levels, even in the presence of the inflammatory cytokine TNF-α. KLF2 attenuates cell migration by affecting multiple genes including VEGFR2 and the potent antimigratory SEMA3F. The distribution of Weibel-Palade bodies in cultured cell populations is normalized at the single-cell level without interfering with their regulated, RalA-dependent release. In contrast, thrombin-induced release of Weibel-Palade bodies is significantly attenuated, consistent with the proposed role of VWF release at low–shear stress regions of the vasculature in atherosclerosis. These results establish that KLF2 acts as a central transcriptional switch point between the quiescent and activated states of the adult endothelial cell.
Age and acute myeloid leukemia
Authors: Appelbaum Frederick R. , Gundacker Holly , Head David R. , Slovak Marilyn L. , Willman Cheryl L. , Godwin John E. , Anderson Jeanne E. , Petersdorf Stephen H.
Published: February 2006

We conducted a retrospective analysis of 968 adults with acute myeloid leukemia (AML) on 5 recent Southwest Oncology Group trials to understand how the nature of AML changes with age. Older study patients with AML presented with poorer performance status, lower white blood cell counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. The percentage of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. The increased incidence of unfavorable cytogenetics contributed to their poorer outcome, and, within each cytogenetic risk group, treatment outcome deteriorated markedly with age. Finally, the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy. The distinct biology and clinical responses seen argue for age-specific assessments when evaluating therapies for AML.
Regulation of human lung epithelial cell numbers by diesel exhaust particles
Authors: Bayram H. , Ito K. , Issa R. , Ito M. , Sukkar M. , Chung K. F.
Published: February 2006

Particulate air pollution is associated with respiratory morbidity and has cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined.

When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP (5–200 µg·mL−1) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 µg·mL−1) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G0/1arrest. DEP also reduced the increase in apoptotic cells, as defined by double expression of annexin V/PI, observed after serum starvation (from 28.35 to 15.46%). The antioxidants,N-acetylcysteine (NAC; 33 mM) and AEOL10113 (10–100 µM), the N-terminal c-jun kinase inhibitor, SP600125 (33 µM), and nuclear factor-κB inhibitor, SN50 (33 µM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G0/1and increase in cells in the S and G2/M phases. Expression of p21CIP1/WAF1mRNA and protein seen with serum starvation was reduced by DEP.

In conclusion, diesel exhaust particles prevented serum starvation-led decreases in A549 epithelial cells by inducing cell cycle progression and preventing apoptosis, processes involving oxidative stress, inhibition of p21CIP1/WAF1expression and stimulation of N-terminal c-jun kinase and nuclear factor-κB. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.
Formoterol Turbuhaler as reliever medication in patients with acute asthma
Authors: Rubinfeld A. R. , Scicchitano R. , Hunt A. , Thompson P. J. , Van Nooten A. , Selroos O.
Published: February 2006

The aim of this study was to compare the efficacy and safety of formoterolversussalbutamol as reliever medication in patients presenting at an emergency dept with acute asthma.

A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler® 4.5 µg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 µg (metered dose), patients received a total of formoterol Turbuhaler® 36 µg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 µg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic β2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min.

At 45 min, mean increases in FEV1expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval −2.0–8.0). Transient increases in systemic β2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events.

In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler® 36 µg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 µg in the number of patients studied.
New aspects of airway mechanics in pre-term infants
Authors: Henschen M. , Stocks J. , Brookes I. , Frey U.
Published: February 2006

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (far,1), is related to airway wall mechanics.

The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values offar,1from 18 pre-term (post-conceptional age 32–37 weeks, weight 1,730–2,910 g) and 18 full-term infants (42–47 weeks, 3,920–5,340 g).

Among the pre-term infants, there was good short-term repeatability offar,1within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures offar,1after 3–8 h were relatively wide (−41 Hz; 37 Hz).far,1was significantly lower in pre-term infants (199versus257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue.

Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.
Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients
Authors: Robinson G. V. , Smith D. M. , Langford B. A. , Davies R. J. O. , Stradling J. R.
Published: February 2006

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence.

Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH2O pressure). The second months' alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable.

There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd8.1), and -1.1 mmHg (sd8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9– -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4)versussham (-0.3), and difference -1.2 (95% CI -2.0– -0.4), but no change in objective sleepiness.

In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.
Physiological effects of vibration in subjects with cystic fibrosis
Authors: McCarren B. , Alison J. A.
Published: February 2006

The physiological mechanisms by which vibration and other physiotherapy interventions may clear secretions in subjects with cystic fibrosis are unknown. The main aim of this study was to compare the expiratory flow rates and frequencies of airflow oscillation of vibration to those of Acapella®, Flutter®, positive expiratory pressure and percussion.

Respiratory flow rates were measured during interventions, the order of which was randomised. The oscillation of the airflow of the interventions was determined by frequency spectral analysis.

In 18 young adult subjects with cystic fibrosis, the mean peak expiratory flow rate of vibration was greater than Flutter®, percussion, Acapella® and positive expiratory pressure. The mean±sdof the oscillation of the airflow of vibration (8.4±0.4 Hz) was lower than Acapella® (13.5±1.7 Hz) and Flutter® (11.3±1.5 Hz) but similar to percussion (7.3±0.3 Hz).

Theoretically, the higher peak expiratory flow rate of vibration compared to the other physiotherapy interventions may promote secretion clearance. In addition, the frequency of oscillation of vibration was within the range demonstrated to increase mucus transport. This study has provided some evidence for the physiological rationale for the use of vibration to aid secretion clearance.
Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis
Authors: Barker M. , Hengst M. , Schmid J. , Buers H-J. , Mittermaier B. , Klemp D. , Koppmann R.
Published: February 2006

Inflammatory mediators in the exhaled breath are receiving growing medical interest as noninvasive disease markers. Volatile organic compounds have been investigated in this context, but clinical information and methodological standards are limited.

The levels of ethane, propane,n-pentane, methanol, ethanol, 2-propanol, acetone, isoprene, benzene, toluene, dimethyl sulphide (DMS) and limonene were measured in repeated breath samples from 20 cystic fibrosis patients and 20 healthy controls (aged 8–29 yrs). Three end-exhaled and one ambient air sample were collected per person and analysed on a customised gas chromatography system.

Intra-subject coefficients of variation ranged between 9 and 34%, and hydrocarbon breath levels were influenced by their inspired concentrations. The alveolar gradient for pentane was higher in cystic fibrosis patients than in healthy controls (0.36versus0.21 ppb) and inversely proportional to forced expiratory volume in one second; highest values were observed in patients with pulmonary exacerbations (0.73versus0.24 ppb). Cystic fibrosis patients also exhibited a lower output of DMS (3.9versus7.6 ppb). Group differences were not significant for ethane and the remaining substances.

It was concluded that chemical breath analysis for volatile organic compounds is feasible and may hold potential for the noninvasive diagnosis and follow-up of inflammatory processes in cystic fibrosis lung disease.
Low levels of air pollution induce changes of lung function in a panel of schoolchildren
Authors: Moshammer H. , Hutter H-P. , Hauck H. , Neuberger M.
Published: February 2006

In search of sensitive screening parameters for assessing acute effects of ambient air pollutants in young schoolchildren, the impact of 8-h average air pollution before lung function testing was investigated by oscillatory measurements of resistance and spirometry with flow–volume loops.

At a central elementary school in Linz, the capital of Upper Austria, 163 children aged 7–10 yrs underwent repeated examinations at the same time of day during 1 school year, yielding a total of 11–12 lung function tests per child. Associations to mass concentrations of particulate matter and nitrogen dioxide (NO2) measured continuously at a nearby monitoring station were tested, applying the Generalised Estimating Equations model.

Reductions per 10 µg·m−3(both for particles and for NO2) were in the magnitude of 1% for most lung function parameters. The most sensitive indicator for acute effects of combustion-related pollutants was a change in maximal expiratory flow in small airways. NO2at concentrations below current standards reduced (in the multipollutant model) the forced expiratory volume in one second by 1.01%, maximal instantaneous forced flow when 50% of the forced vital capacity remains to be exhaled (MEF50%) by 1.99% and MEF25%by 1.96%. Peripheral resistance increased by 1.03% per 10 µg·m−3of particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm (PM2.5). Resistance is less influenced by the child's cooperation and should be utilised more often in environmental epidemiology when screening for early signs of small airway dysfunction from urban air pollution, but cannot replace the measurement of MEF50%and MEF25%. In the basic model, the reduction of these parameters per 10 µg·m−3was highest for NO2, followed by PM1, PM2.5and PM10, while exposure to coarse dust (PM10–PM2.5) did not change end-expiratory flow significantly.

All acute effects of urban air pollution found on the lung function of healthy pupils were evident at levels below current European limit values for nitrogen dioxide. Thus, planned reduction of nitrogen dioxide emission (Euro 5; vehicles that comply with the emission limits as defined in Directive 99/96/EC) of 20% in 2010 would seem to be insufficient.
Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness
Authors: Green R. H. , Brightling C. E. , McKenna S. , Hargadon B. , Neale N. , Parker D. , Ruse C. , Hall I. P. , Pavord I. D.
Published: February 2006

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids.

A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 μgb.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 μgb.i.d., with each treatment separated by a 4-week washout period.

The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5–0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7–1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2–2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second.

In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.
Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats
Authors: Kobayashi M. , Nasuhara Y. , Kamachi A. , Tanino Y. , Betsuyaku T. , Yamaguchi E. , Nishihira J. , Nishimura M.
Published: February 2006

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that reportedly counteracts the anti-inflammatory effect of endogenous glucocorticoids. There have only been a few reports that demonstrate a potential link between MIF and bronchial asthma. In an attempt to further clarify the precise role of MIF in asthma, the present authors examined the effect of anti-MIF antibody (Ab) on airway inflammation and airway hyperresponsiveness in an ovalbumin-immunised rat asthma model.

Actively immunised Brown Norway rats received ovalbumin inhalation with or without treatment of anti-MIF Ab. The levels of MIF in bronchoalveolar lavage fluid were significantly elevated after the ovalbumin challenge.

An immunohistochemical study revealed positive immunostaining for MIF in bronchial epithelium, even in nonsensitised rats, and the MIF staining in bronchial epithelium was enhanced after the ovalbumin challenge. Anti-MIF Ab significantly decreased the number of total cells, neutrophils and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin-challenged rats, and also attenuated the ovalbumin-induced airway hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF Ab did not affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF Ab did not suppress immunisation itself.

The results indicate that macrophage migration inhibitory factor plays a crucial role in airway inflammation and airway hyperresponsiveness in asthma.
Telomerase activation in a model of lung adenocarcinoma
Authors: Suau F. , Cottin V. , Archer F. , Croze S. , Chastang J. , Cordier G. , Thivolet-Béjui F. , Mornex J-F. , Leroux C.
Published: February 2006

Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated.

Lung tissues were collected from sheep with a histopathological diagnosis of OPA or controls. Epithelial cell cultures were derivedin vitrofrom lung tissues. Telomerase activity was evaluated using the telomeric repeat amplification protocol method. Phosphorylation of Akt was detected by Western blotting.

Telomerase activity was significantly higher in OPA lung tissues compared to control lung tissues. A high telomerase activity was detected in eight out of 12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours.

Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation. Telomerase may inhibit cellular senescence and contribute to the accumulation of tumour cells in mixed adenocarcinoma with a bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.
Wnt signalling in lung development and diseases
Authors: Pongracz Judit E , Stockley Robert A
Published: February 2006

There are several signalling pathways involved in lung organogenesis including Notch, TGFβ /BMP, Sonic hedgehog (Shh), FGF, EGF, and Wnt. Despite the widely acknowledged significance of Wnt signalling in embryonic lung development, the role of different Wnt pathways in lung pathologies has been slow to emerge.

In this review, we will present a synopsis of current Wnt research with particular attention paid to the role of Wnt signals in lung development and in pulmonary diseases.
Restoration of diaphragmatic function after diaphragm reinnervation by inferior laryngeal nerve; experimental study in rabbits
Authors: Derrey Stephane , verin Eric , Laquerrière Annie , de Barros Angelique Boishardy , Lacoume Yann , Fréger Pierre , Marie Jean Paul
Published: February 2006

Objectives

To assess the possibilities of reinnervation in a paralyzed hemidiaphragm via an anastomosis between phrenic nerve and inferior laryngeal nerve in rabbits. Reinnervation of a paralyzed diaphragm could be an alternative to treat patients with ventilatory insufficiency due to upper cervical spine injuries.

Material and method

Rabbits were divided into five groups of seven rabbits each. Groups I and II were respectively the healthy and the denervated control groups. The 3 other groups were all reinnervated using three different surgical procedures. In groups III and IV, phrenic nerve was respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the trunk of the inferior laryngeal nerve. In group V, the fifth and fourth cervical roots were respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the nerve of the sternothyroid muscle (originating from the hypoglossal nerve). Animals were evaluated 4 months later using electromyography, transdiaphragmatic pressure measurements, sonomicrometry and histological examination.

Results

A poor inspiratory activity was found in quiet breathing in the reinnervated groups, with an increasing pattern of activity during effort. In the reinnervated groups, transdiaphragmatic pressure measurements and sonomicrometry were higher in group III with no significant differencewith groups IV and V.

Conclusion

Inspiratory contractility of an hemidiaphragm could be restored with immediate anastomosis after phrenic nerve section between phrenic nerve and inferior laryngeal nerve.
Limited β2-adrenoceptor haplotypes display different agonist mediated airway responses in asthmatics
Authors: van Veen Anneke , Wierenga Eddy A , Westland Robert , Weller Frank R , Hart Guus AM , Jansen Henk M , Jonkers René E
Published: February 2006

Background

In vitroand somein vivostudies suggested that genetic haplotypes may have an impact on β2-agonist mediated airway responses in asthmatics. Due to strong linkage disequilibrium the single nucleotide polymorphisms (SNPs) in the β2-adrenoceptor gene result in only a limited number of haplotypes. We intended to evaluate the impact of β2-adrenoceptor haplotypes on β2-agonist mediated airway responses and the development of tolerance in mild to moderate asthmatics.

Methods

Patients were genotyped for the part of the β2-adrenoceptor gene with a known bearing on receptor function and regulation. Cumulative dose response curves of fenoterol versus PD20methacholine and FEV1were constructed after 2 week treatment periods with either terbutaline or placebo in a double blind, randomised and cross-over design. Analysis of the dose response curves was based on a repeated measurement analysis of covariance.

Results

In our study population comprising 45 asthmatic patients, we found three limited allelic haplotypes, resulting in six different genotypes. Our data support the existence of differences between these six genotypes both in the shape of the dose response relationship of the β2-adrenoceptor agonist fenoterol as well as in the propensity to develop tolerance for these effects by pre-treatment with terbutaline. However, this could only be substantiated for the endpoint PD20methacholine.

Conclusion

Between β2-adrenoceptor genotypes differences exist both in baseline β2-agonist induced airway responses as well as in the propensity to develop tolerance during maintenance β2-agonist therapy. The net differences after two weeks of therapy are, however, of magnitudes that are unlikely to be of clinical significance.
Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: A cytometric study
Authors: Fabbri Francesco , Carloni Silvia , Brigliadori Giovanni , Zoli Wainer , Lapalombella Rosa , Marini Marina
Published: February 2006

Background

Despite the great advances in the understanding of programmed cell death, little attention has been paid to the sequence of the events that characterise it. In particular, the course of apoptotic events induced by microtubule-interfering agents such as taxanes is poorly understood. In order to increase such knowledge, we studied a number of independent biochemical and cytological modifications using cytometric methods in a bladder cancer cell line treated with the second generation taxane, docetaxel.

Results

Within a few hours, drug treatment had induced mitochondrial membrane transition, cell shrinkage and a decrease in granularity. Cell cycle was almost completely blocked in G2/M phase within 24 hours. The hypodiploid peak started to become prominent 48 hours after the treatment. At the same time, the appearance of a DNA ladder demonstrated caspase-dependent chromatin fragmentation. Concurrently, specific cell surface modifications took place, involving at first glycoprotein syalilation and later phospholipid asymmetry. DNA fragmentation was subsequently detected by TUNEL assay. Over time, cell membranes became permeable to propidium iodide. A very similar time-course of apoptotic events was found after treatment of a myelomonocytic cell line with the same drug.

Conclusion

After discussing some characteristics of the methods employed and their limitations, a succession of apoptotic events over time is suggested, in which the collapse of mitochondrial transmembrane potential (Δψm) is the earliest sign of apoptosis.
D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells
Authors: Ryabinina Olga P , Subbian Ezhilkani , Iordanov Mihail S
Published: February 2006

Background

The family of c-Jun NH2-terminal kinases (JNK) plays important roles in embryonic development and in cellular responses to stress. Toxic metals and their compounds are potent activators of JNK in mammalian cells. The mechanism of mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced oxidative stress. The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK).

Results

UsingDrosophila melanogasterS2 cells, we demonstrate here that cadmium and arsenite activateDrosophilaJNK (D-JNK) via oxidative stress as well, thus providing a simpler model system to study JNK signaling. To elucidate the signaling pathways that lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA interference (RNAi) to knock down thirteen upstream regulators of D-JNK, either singly or in combinations of up to seven at a time.

Conclusion

D-MEKK1, the fly orthologue of mammalian MEKK4/MTK1, andHemipterous/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite.
The Tgif2 gene contains a retained intron within the coding sequence
Authors: Melhuish Tiffany A , Wotton David
Published: February 2006

Background

TGIF and TGIF2 are homeodomain proteins, which act as TGFβ specific Smad transcriptional corepressors. TGIF recruits general repressors including mSin3 and CtBP. The related TGIF2 protein functions in a similar manner, but does not bind CtBP. In addition to repressing TGFβ activated gene expression, TGIF and TGIF2 repress gene expression by binding directly to DNA. TGIF and TGIF2 share two major blocks of similarity, encompassing the homeodomain, and a conserved carboxyl terminal repression domain. Here we characterize two splice variants of the Tgif2 gene from mouse and demonstrate that the Tgif2 gene contains a retained intron.

Results

By PCR from mouse cDNA, we identified two alternate splice forms of the Tgif2 gene. One splice variant encodes the full length 237 amino acid Tgif2, whereas the shorter form results in the removal of 39 codons from the centre of the coding region. The generation of this alternate splice form occurs with the mouse RNA, but not the human, and both splice forms are present in all mouse tissues analyzed. Human and mouse Tgif2 coding sequences contain a retained intron, which in mouse Tgif2 is removed by splicing from around 25–50% of RNAs, as assessed by RT-PCR. This splicing event is dependent on sequences within the mouse Tgif2 coding sequence. Both splice forms of mouse Tgif2 encode proteins which are active transcriptional repressors, and can repress both TGFβ dependent and independent transcription. In addition, we show that human and mouse Tgif2 interact with the transcriptional corepressor mSin3.

Conclusion

These data demonstrate that the Tgif2 gene contains a retained intron, within the second coding exon. This retained intron is not removed from the human mRNA at a detectable level, but is spliced out in a significant proportion of mouse RNAs. This alternate splicing is dependent entirely on sequences within the mouse Tgif2 coding sequence, suggesting the presence of an exonic splicing enhancer. Both splice forms of mouse Tgif2 produce proteins which are functional transcriptional repressors.
NADPH- Diaphorase positive cardiac neurons in the atria of mice. A morphoquantitative study
Authors: Maifrino Laura Beatriz Mesiano , Liberti Edson Aparecido , Castelucci Patrícia , De Souza Romeu Rodrigues
Published: February 2006

Background

The present study was conducted to determine the location, the morphology and distribution of NADPH-diaphorase positive neurons in the cardiac nerve plexus of the atria of mice (ASn). This plexus lies over the muscular layer of the atria, dorsal to the muscle itself, in the connective tissue of the subepicardium. NADPH- diaphorase staining was performed on whole-mount preparations of the atria mice. For descriptive purposes, all data are presented as means ± SEM.

Results

The majority of the NADPH-diaphorase positive neurons were observed in the ganglia of the plexus. A few single neurons were also observed. The number of NADPH-d positive neurons was 57 ± 4 (ranging from 39 to 79 neurons). The ganglion neurons were located in 3 distinct groups: (1) in the region situated cranial to the pulmonary veins, (2) caudally to the pulmonary veins, and (3) in the atrial groove. The largest group of neurons was located cranially to the pulmonary veins (66.7%). Three morphological types of NADPH-diaphorase neurons could be distinguished on the basis of their shape: unipolar cells, bipolar cells and cells with three processes (multipolar cells). The unipolar neurons predominated (78.9%), whereas the multipolar were encountered less frequently (5,3%). The sizes (area of maximal cell profile) of the neurons ranged from about 90 μm2to about 220 μm2. Morphometrically, the three types of neurons were similar and there were no significant differences in their sizes. The total number of cardiac neurons (obtained by staining the neurons with NADH-diaphorase method) was 530 ± 23. Therefore, the NADPH-diaphorase positive neurons of the heart represent 10% of the number of cardiac neurons stained by NADH.

Conclusion

The obtained data have shown that the NADPH-d positive neurons in the cardiac plexus of the atria of mice are morphologically different, and therefore, it is possible that the function of the neurons may also be different.
Room for improvement? A survey of the methods used in systematic reviews of adverse effects
Authors: Golder Su , Loke Yoon , McIntosh Heather M
Published: February 2006

Background

Although the methods for conducting systematic reviews of efficacy are well established, there is much less guidance on how systematic reviews of adverse effects should be performed.

Methods

In order to determine where methodological research is most needed to improve systematic reviews of adverse effects of health care interventions, we conducted a descriptive analysis of systematic reviews published between 1994 and 2005. We searched the Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Database of Systematic Reviews (CDSR) to identify systematic reviews in which the primary outcome was an adverse effect or effects. We then extracted data on many of the elements of the systematic review process including: types of interventions studied, adverse effects of interest, resources searched, search strategies, data sources included in reviews, quality assessment of primary data, nature of the data analysis, and source of funding.

Results

256 reviews were included in our analysis, of which the majority evaluated drug interventions and pre-specified the adverse effect or effects of interest. A median of 3 resources were searched for each review and very few reviews (13/256) provided sufficient information to reproduce their search strategies. Although more than three quarters (185/243) of the reviews sought to include data from sources other than randomised controlled trials, fewer than half (106/256) assessed the quality of the studies that were included. Data were pooled quantitatively in most of the reviews (165/256) but heterogeneity was not always considered. Less than half (123/256) of the reviews reported on the source of funding.

Conclusion

There is an obvious need to improve the methodology and reporting of systematic reviews of adverse effects. The methodology around identification and quality assessment of primary data is the main concern.