bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThere 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

AbstractObjectivesTo 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 methodRabbits 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.ResultsA 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.ConclusionInspiratory 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

AbstractBackgroundIn 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.MethodsPatients 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.ResultsIn 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.ConclusionBetween 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

AbstractBackgroundDespite 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.ResultsWithin 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.ConclusionAfter 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

AbstractBackgroundThe 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).ResultsUsingDrosophila 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.ConclusionD-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

Abstract

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

Abstract

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

Abstract

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.
A novel cell immunoassay to measure survival of motor neurons protein in blood cells
Authors: Kolb Stephen J , Gubitz Amelie K , Olszewski Robert F , Ottinger Elizabeth , Sumner Charlotte J , Fischbeck Kenneth H , Dreyfuss Gideon 
Published: February 2006

Abstract

Background
The motor neuron degenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN) gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples.

Methods
We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody.

Results
SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity.

Conclusion
SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials.
Visual fields in patients who have undergone vitrectomy for complications of diabetic retinopathy. A prospective study
Authors: Barsam Allon , Laidlaw Alistair 
Published: February 2006

Abstract

Backround
To determine the extent of visual field loss in patients who had required a pars plana vitrectomy secondary to complications of proliferative diabetic retinopathy.

Methods
Patients that had undergone a vitrectomy on at least one eye for treatment of either vitreous haemorrhage or tractional retinal detachment were selected for study. ETDRS acuity and Humphrey binocular Esterman visual field testing were performed and compared to the minimum standards for safe driving as defined by the Royal College of Ophthalmologists in 1999. In addition to this Goldman kinetic visual fields using a III4e and V4e stimulus size and central 24-2 threshold test with the SITA-fast strategy were performed on the vitrectomised eye.

Results
20 patients (n = 20) were recruited. Mean visual acuity in the eye being tested was 0.20 (Snellen 6/9.5). Results from the Humphrey field analyzer showed a mean number of abnormal stimulus locations of 71.2% (p < 0.005). 70% of patients had sufficient binocular acuity to drive and of these 71.4% were shown not to have a minimum visual field for safe driving on binocular Esterman field analysis.

Conclusion
Vitrectomy potentially allows retention/restoration of good visual acuity in patients with complications of proliferative diabetic retinopathy. However patients may be suffering from unrecognized visual impairment consequent upon extensive visual field loss which in over two thirds of patients may be sufficiently severe to preclude safe driving.
The effect of verbalization strategy on wisconsin card sorting test performance in schizophrenic patients receiving classical or atypical antipsychotics
Authors: Rossi Alessandro , Daneluzzo Enrico , Tomassini Annarita , Struglia Francesca , Cavallaro Roberto , Smeraldi Enrico , Stratta Paolo 
Published: February 2006

AbstractBackgroundA number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed.The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST) remediation, in subjects on classical vs atypical antipsychotic (AP) treatment.MethodsSixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization) administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable) and AP treatment (i.e. atypical vs. classical).ResultsSubjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs.ConclusionSubjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.