bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement
Authors: Solovic I. , Sester M. , Gomez-Reino J.J. , Rieder H.L. , Ehlers S. , Milburn H.J. , Kampmann B. , Hellmich B. , Groves R. , Schreiber S. , Wallis R.S. , Sotgiu G. , Schölvinck E.H. , Goletti D. , Zellweger J.P. , Diel R. , Carmona L. , Bartalesi F. , Ravn P. , Bossink A. , Duarte R. , Erkens C. , Clark J. , Migliori G.B. , Lange C. 
Published: June 2010

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette–Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection withMycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistentM. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB.This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.
Valproate–doxorubicin: promising therapy for progressing mesothelioma. A phase II study
Authors: Scherpereel A. , Berghmans T. , Lafitte J.J. , Colinet B. , Richez M. , Bonduelle Y. , Meert A.P. , Dhalluin X. , Leclercq N. , Paesmans M. , Willems L. , Sculier J.P. 
Published: June 2010

No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy.In vitrodata suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum-based chemotherapy.Treatment consisted of doxorubicin (60 mg·m-2) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed.From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) ≥80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3–25%), all in patients with PS 80–100. The best disease control rate was 36% (95% CI 22–51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60–70).Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80–100) patients with refractory or recurrent MM, for which no standard therapy was available.
Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function
Authors: Duong-Quy S. , Dao P. , Hua-Huy T. , Guilluy C. , Pacaud P. , Dinh-Xuan A.T. 
Published: June 2010

Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function.Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought.Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls.Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.
Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension
Authors: Dahal B.K. , Kosanovic D. , Pamarthi P.K. , Sydykov A. , Lai Y-J. , Kast R. , Schirok H. , Stasch J-P. , Ghofrani H.A. , Weissmann N. , Grimminger F. , Seeger W. , Schermuly R.T. 
Published: June 2010

An accumulating body of evidence incriminates Rho kinase (ROCK) in the pathogenesis of pulmonary hypertension (PH). The therapeutic efficacy of azaindole-1, a novel highly selective and orally active ROCK inhibitor, has not yet been investigated in PH.This study aimed to investigate the effects of azaindole-1 on 1) acute hypoxic pulmonary vasoconstriction (HPV), 2) proliferation of pulmonary arterial smooth muscle cells (PASMCs) and 3) animal models of PH.Azaindole-1 significantly inhibited HPV in isolated, ventilated and buffer-perfused murine lungs and proliferation of primary rat PASMCsin vitro. Azaindole-1 was administered orally from 21 to 35 days after monocrotaline (MCT) injection in rats and hypoxic exposure in mice. Azaindole-1 (10 and 30 mg per kg body weight per day in rats and mice, respectively) significantly improved haemodynamics and right ventricular hypertrophy. Moreover, the medial wall thickness and muscularisation of peripheral pulmonary arteries were ameliorated. Azaindole-1 treatment resulted in a decreased immunoreactivity for phospho-myosin phosphatase target subunit 1 and proliferating cell nuclear antigen in pulmonary vessels of MCT-injected rats, suggesting an impaired ROCK activity and reduced proliferating cells.Azaindole-1 provided therapeutic benefit in experimental PH, and this may be attributable to its potent vasorelaxant and antiproliferative effects. Azaindole-1 may offer a useful approach for treatment of PH.
Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation
Authors: Edlmayr J. , Niespodziana K. , Popow-Kraupp T. , Krzyzanek V. , Focke-Tejkl M. , Blaas D. , Grote M. , Valenta R. 
Published: June 2010

Human rhinoviruses (HRVs) are the major cause of the common cold and account for 30–50% of all acute respiratory illnesses. Although HRV infections are usually harmless and invade only the upper respiratory tract, several studies demonstrate that HRV is involved in the exacerbation of asthma.VP1 is one of the surface-exposed proteins of the viral capsid that is important for the binding of rhinoviruses to the corresponding receptors on human cells. Here we investigated its potential usefulness for vaccination against the common cold.We expressed VP1 proteins from two distantly related HRV strains, HRV89 and HRV14, inEscherichia coli. Mice and rabbits were immunised with the purified recombinant proteins.The induced antibodies reacted with natural VP1 and with whole virus particles as shown by immunoblotting and immunogold electron microscopy. They exhibited strong cross-neutralising activity for different HRV strains. Therefore, recombinant VP1 may be considered a candidate HRV vaccine to prevent HRV-induced asthma exacerbations.
Lung exposure to nanoparticles modulates an asthmatic response in a mouse model
Authors: Hussain S. , Vanoirbeek J.A.J. , Luyts K. , De Vooght V. , Verbeken E. , Thomassen L.C.J. , Martens J.A. , Dinsdale D. , Boland S. , Marano F. , Nemery B. , Hoet P.H.M. 
Published: June 2010

The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO2) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma.On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone–olive oil (AOO) on the dorsum of both ears (20 μL). On day 14, the mice were oropharyngeally dosed with 40 μL of a NP suspension (0.4 mg·mL−1(∼0.8 mg·kg−1) TiO2or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 μL). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed.NP exposure in sensitised mice led to a two- (TiO2) or three-fold (Au) increase in AHR, and a three- (TiO2) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation.In conclusion, these results show that a low, intrapulmonary doses of TiO2or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.
Exercise is associated with improved asthma control in adults
Authors: Dogra S. , Kuk J.L. , Baker J. , Jamnik V. 
Published: June 2010

Global asthma control levels are suboptimal. The influence of regular exercise on asthma control is unclear.We assessed the effects of a 12-week supervised exercise intervention followed by 12 weeks of self-administered exercise on adults with partially controlled asthma (n = 21) and matched controls (n = 15). Assessments were conducted at baseline and week 12 for both the exercise and control group, and again at week 24 for the exercise group.There was a significant treatment effect on asthma control in the exercise group, as measured by the Asthma Control Questionnaire (ACQ), from baseline to week 12, compared with the control group. A clinically significant improvement (0.5 increase in ACQ score) was observed for asthma quality of life and ACQ in the exercise group from baseline to week 12. There was a significant improvement in aerobic fitness from baseline to week 24 in the exercise group.In conclusion, a 12-week supervised exercise intervention led to improvements in asthma control and quality of life in partially controlled asthmatics motivated to exercise. These improvements were maintained, while aerobic fitness and perceived asthma control significantly improved over an additional 12 weeks of self-administered exercise. These findings indicate that a structured exercise intervention can improve asthma control.
Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study
Authors: Ghofrani H.A. , Hoeper M.M. , Halank M. , Meyer F.J. , Staehler G. , Behr J. , Ewert R. , Weimann G. , Grimminger F. 
Published: June 2010

We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH; n = 42) or pulmonary arterial hypertension (PAH; n = 33) in World Health Organization (WHO) functional class II/III.In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0–2.5 mgt.i.d.titrated according to systemic systolic blood pressure (SBP). Primary end-points were safety and tolerability; pharmacodynamic changes were secondary end-points.Riociguat was generally well tolerated. Asymptomatic hypotension (SBP <90 mmHg) occurred in 11 patients, but blood pressure normalised without dose alteration in nine and after dose reduction in two. Median 6-min walking distance increased in patients with CTEPH (55.0 m from baseline (390 m); p<0.0001) and PAH (57.0 m from baseline (337 m); p<0.0001); patients in functional class II or III and bosentan pre-treated patients showed similar improvements. Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm−5from baseline (709 dyn·s·cm−5; p<0.0001). 42 (56%) patients were considered to have experienced drug-related adverse events (AEs; 96% mild or moderate). Dyspepsia, headache and hypotension were the most frequent AEs. Study discontinuation because of AEs was 4%.These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms and pulmonary haemodynamics in CTEPH and PAH. Randomised controlled trials are underway.
Determinants of change in airway reactivity over 11 years in the SAPALDIA population study
Authors: Curjuric I. , Zemp E. , Dratva J. , Ackermann-Liebrich U. , Bridevaux P-O. , Bettschart R.W. , Brutsche M. , Frey M. , Gerbase M.W. , Knöpfli B. , Künzli N. , Pons M. , Schwartz J. , Schindler C. , Rochat T. ,   the SAPALDIA team
Published: June 2010

We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29–72 yrs at follow-up).The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine.Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged <50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found.Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation–perfusion disturbances related to cumulative lifetime exposures.
Involvement of p63 in the herpes simplex virus-1-induced demise of corneal cells
Authors: Orosz László , Gallyas Éva , Kemény Lajos , Mándi Yvette , Facskó Andrea , Megyeri Klára 
Published: June 2010

AbstractBackgroundThe transcription factor p63 plays a pivotal role in the development and maintenance of epithelial tissues, including the ocular surface. In an effort to gain insight into the pathogenesis of keratitis caused by HSV-1, we determined the expression patterns of the p63 and Bax proteins in the Staatens Seruminstitute Rabbit Cornea cell line (SIRC).MethodsSIRC cells were infected with HSV-1 at various multiplicities and maintained for different periods of time. Virus replication was measured by indirect immunofluorescence assay and Western blot analysis. Cell viability was determined by MTT assay. The apoptotic response of the infected cells was quantified by ELISA detecting the enrichment of nucleosomes in the cytoplasm. Western blot analysis was used to determine the levels of p63 and Bax proteins.ResultsIndirect immunofluorescence assays and Western blot analyses demonstrated the presence of HSV-1 glycoprotein D (gD) in the infected SIRC cell line, and the pattern of gD expression was consistent with efficient viral replication. The results of MTT and ELISA assays showed that HSV-1 elicited a strong cytopathic effect, and apoptosis played an important role in the demise of the infected cells. Mock-infected SIRC cells displayed the constitutive expression of ΔNp63α. The expressions of the Bax-β and TAp63γ isoforms were considerably increased, whereas the level of ΔNp63α was decreased in the HSV-1-infected SIRC cells. Experiments involving the use of acyclovir showed that viral DNA replication was necessary for the accumulation of TAp63γ.ConclusionThese data suggest that a direct, virus-mediated cytopathic effect may play an important role in the pathogenic mechanism of herpetic keratitis. By disturbing the delicate balance between the pro-survival ΔN and the pro-apoptotic TA isoforms, HSV-1 may cause profound alterations in the viability of the ocular cells and in the tissue homeostasis of the ocular surface.
Rule-based spatial modeling with diffusing, geometrically constrained molecules
Authors: Gruenert Gerd , Ibrahim Bashar , Lenser Thorsten , Lohel Maiko , Hinze Thomas , Dittrich Peter 
Published: June 2010

Abstract

Background
We suggest a new type of modeling approach for the coarse grained, particle-based spatial simulation of combinatorially complex chemical reaction systems. In our approach molecules possess a location in the reactor as well as an orientation and geometry, while the reactions are carried out according to a list of implicitly specified reaction rules. Because the reaction rules can contain patterns for molecules, a combinatorially complex or even infinitely sized reaction network can be defined.
For our implementation (based on LAMMPS), we have chosen an already existing formalism (BioNetGen) for the implicit specification of the reaction network. This compatibility allows to import existing models easily, i.e., only additional geometry data files have to be provided.

Results
Our simulations show that the obtained dynamics can be fundamentally different from those simulations that use classical reaction-diffusion approaches like Partial Differential Equations or Gillespie-type spatial stochastic simulation. We show, for example, that the combination of combinatorial complexity and geometric effects leads to the emergence of complex self-assemblies and transportation phenomena happening faster than diffusion (using a model of molecular walkers on microtubules). When the mentioned classical simulation approaches are applied, these aspects of modeled systems cannot be observed without very special treatment. Further more, we show that the geometric information can even change the organizational structure of the reaction system. That is, a set of chemical species that can in principle form a stationary state in a Differential Equation formalism, is potentially unstable when geometry is considered, and vice versa.

Conclusions
We conclude that our approach provides a new general framework filling a gap in between approaches with no or rigid spatial representation like Partial Differential Equations and specialized coarse-grained spatial simulation systems like those for DNA or virus capsid self-assembly.
Optimization of somatic cell injection in the perspective of nuclear transfer in goldfish
Authors: Bail Pierre-Yves Le , Depince Alexandra , Chenais Nathalie , Mahe Sophie , Maisse Gerard , Labbe Catherine 
Published: June 2010

Abstract

Background
Nuclear transfer has the potential to become one strategy for fish genetic resources management, by allowing fish reconstruction from cryopreserved somatic cells. Survival rates after nuclear transfer are still low however. The part played by unsuitable handling conditions is often questioned, but the different steps in the procedure are difficult to address separately. In this work led on goldfish (Carassius auratus), the step of somatic cells injection was explored. Non-enucleated metaphase II oocytes were used as a template to explore the toxicity of the injection medium, to estimate the best location where the cell should be injected, and to assess the delay necessary between cell injection and oocyte activation.

Results
Trout coelomic fluid was the most suitable medium to maintain freshly spawned oocytes at the metaphase II stage during oocyte manipulation. Oocytes were then injected with several media to test their toxicity on embryo development after fertilization. Trout coelomic fluid was the least toxic medium after injection, and the smallest injected volume (10 pL) allowed the same hatching rates as the non injected controls (84.8% ± 23). In somatic cell transfer experiments using non enucleated metaphase II oocytes as recipient, cell plasma membrane was ruptured within one minute after injection. Cell injection at the top of the animal pole in the oocyte allowed higher development rates than cell injection deeper within the oocyte (respectively 59% and 23% at mid-blastula stage). Embryo development rates were also higher when oocyte activation was delayed for 30 min after cell injection than when activation was induced without delay (respectively 72% and 48% at mid-blastula stage).

Conclusions
The best ability of goldfish oocytes to sustain embryo development was obtained when the carrier medium was trout coelomic fluid, when the cell was injected close to the animal pole, and when oocyte activation was induced 30 min after somatic cell injection. Although the experiments were not designed to produce characterized clones, application of these parameters to somatic cell nuclear transfer experiments in enucleated metaphase II oocytes is expected to improve the quality of the reconstructed embryos.
In-vivo high resolution imaging of optic nerve head drusen using spectral-domain Optical Coherence Tomography
Authors: Murthy Ravi K , Storm Laura , Grover Sandeep , Brar Vikram S , Chalam Kakarla V 
Published: June 2010

Abstract

Background
Optic nerve head drusen (ONHD) are white calcareous deposits, seen either superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT scan and/or visual field examination. The present study describes features of ONHD based on another diagnostic modality, the spectral-domain OCT (Spectralis).

Methods
This is a retrospective case series of 5 patients with bilateral ONHD with a best-corrected visual acuity of 20/20 and no other posterior segment pathology. All the patients underwent fundus photography, fundus autofluorescence, B-scan ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields.

Results
All 5 patients had surface ONHD which were autofluorescent and echodense on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include 'scattered spots with high reflectivity' casting a shadow underneath. The reflectivity can be distinctly differentiated from the blood vessels on the optic nerve. Two patients had an arcuate scotoma on the Humphrey visual fields. No correlation was found between the changes on Spectralis OCT with that of visual field.

Conclusions
Spectralis OCT is another useful ancillary investigation in the diagnosis of ONHD and we describe the features in the present study.