tbuckley/cabot-search huggingface dataset:
Nitrosoglutathione reductase inhibition in the airway epithelium may contribute to lung cancer risk
Authors: Nadzeya Marozkina, David Jones, Sean Yemen, Benjamin Gaston
Journal: European Respiratory Journal (2011)

Background:  S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator. GSNO reductase (GSNOR) depletes airway GSNO; inhibitors are in development for asthma. However, GSNO can be tumorigenic by activating wild-type (wt) Ras though S-nitrosylation. We studied whether decreased GSNO reductase promotes wt Ras S-nitrosylation and activation in the lung.   Methods:  Lung non-small cell cancer lines (H157; Calu-1; H226;Calu-3; H1650; A549) were studied. Ras S-Nitrosylation was studied by biotin substitution and immunoblot. Active GTP-Ras was assayed in a Raf-1RBD-binding ELISA. Certain cells were exposed to 1) 30 ppm NO in a sealed incubator; or 2) S-nitrosocysteine (CSNO, 10 μM), GSH (2mM) and NADH (300 μM) with or without the GSNO reductase inhibitor, C3 (100 μM; 10 min; from P. Sanghani). GSNO reductase  -/-  (from J.S. Stamler) were compared with C57Black6 mice with and without intratracheal ethyl nitrite (EtONO, 10 μM).   Results:  Wt Ras S-nitrosylation was increased relative to expression in cancer cell lines, though expression of was low. NO exposure for 5d, but not 2d, increased Ras S-nitrosylation relative to expression in vitro. S-Nitrosylation of Ras relative to total Ras expression was increased in the lungs of GSNO reductase  -/-  mice; and was increased in wt mice by EtONO. CSNO increased Ras activity. In the H1650 cells, this increase was partially augmented by the C3, though baseline expression and activity of GSNO reductase were low.   Conclusions:  Though loss of GSNO reductase function may benefit asthma, it prevents wt Ras denitrosylation and inactivation. This effect is associated with tumorigenesis and may not be a good strategy for asthma treatment, particularly in smokers.
Endothelium, endocardium, and cardiac contraction
Authors: A. H Henderson, M. J Lewis, A. M Shah, J. A Smith
Journal: Cardiovascular Research (1992)

Journal Article Endothelium, endocardium, and cardiac contraction Get access Andrew H Henderson, Andrew H Henderson Cardiovascular Sciences Research Group, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom: A H Henderson, M J Lewis, A M Shah, J A Smith. Correspondence to Professor Henderson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm J Lewis, Malcolm J Lewis Cardiovascular Sciences Research Group, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom: A H Henderson, M J Lewis, A M Shah, J A Smith. Correspondence to Professor Henderson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ajay M Shah, Ajay M Shah Cardiovascular Sciences Research Group, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom: A H Henderson, M J Lewis, A M Shah, J A Smith. Correspondence to Professor Henderson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerry A Smith Jerry A Smith Cardiovascular Sciences Research Group, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom: A H Henderson, M J Lewis, A M Shah, J A Smith. Correspondence to Professor Henderson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 4, April 1992, Pages 305–308, https://doi.org/10.1093/cvr/26.4.305 Published: 01 April 1992 Article history Received: 24 December 1991 Accepted: 18 February 1992 Published: 01 April 1992
Extracorporeal shockwave therapy for patellar tendinopathy: a review of the literature
Authors: M T van Leeuwen, J Zwerver, I van den Akker-Scheek
Journal: British Journal of Sports Medicine (2008)

Extracorporeal shockwave therapy (EWST) has become a popular treatment for patellar tendinopathy. The purpose of this review was to study the effectiveness of ESWT treatment for patellar tendinopathy; to draft guidelines for an effective treatment protocol of ESWT treatment; and to identify topics for further research.A computerised search of the Medline and Embase databases was conducted on 1 August 2007, to identify studies dealing with the effectiveness of ESWT for patellar tendinopathy.Seven articles describing the effectiveness of ESWT on patellar tendinopathy, all published after 2000, were included. These studies included a total of 283 patients (298 tendons), 204 of whom (215 tendons) were assigned to ESWT treatment. The treatment results were positive but most studies had methodological deficiencies, small numbers and/or short follow-up periods. Method of application and shockwave generation, energy level, number and frequency of treatments, use of (local) anaesthesia and method of localisation were variable.ESWT seems to be a safe and promising treatment for patellar tendinopathy with a positive effect on pain and function. Based on current knowledge it is impossible to recommend a specific treatment protocol. Further basic and clinical research into the working mechanism and effectiveness of ESWT for patellar tendinopathy are necessary.
Platelet activation in nocturnal asthma.
Authors: J F Morrison, S B Pearson, H G Dean, I R Craig, P N Bramley
Journal: Thorax (1991)

Platelet activation may be a factor in the bronchial hyperresponsiveness that characterises asthma. As hyperresponsiveness is increased at night, changes in platelet activation over 24 hours were related to the diurnal changes in peak expiratory flow and plasma catecholamine concentrations in five subjects with asthma and five normal subjects. The effect of muscarinic receptor blockade with intravenous atropine at 0400 hours on these measurements was also studied. Platelet activation, assessed as the ration of beta thromboglobulin to platelet factor 4, was highest when the peak expiratory flow rate was at its lowest in the asthmatic subjects. There was no correlation between platelet activation and plasma catecholamine concentrations. Intravenous atropine did not alter the ratio of beta thromboglobulin to platelet factor 4, suggesting that parasympathetic activity is not the cause of the increased platelet activation at night.
How much asthma is really attributable to atopy?
Authors: N. Pearce, J. Pekkanen, R. Beasley
Journal: Thorax (1999)

In recent decades it has become routine to describe asthma as an atopic disease.A theoretical paradigm has evolved in which allergen exposure produces atopic sensitisation and continued exposure leads to clinical asthma through the development of airways inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction.As Martinez 1 notes, this paradigm has been used with particular insistence with regard to house dust mite allergens, 2 3 but other allergens (cat, cockroach, dog) are also believed to be important.The importance of atopy is most widely accepted for asthma in children whereas, among adults, asthma has traditionally been divided into "extrinsic" and "intrinsic" asthma, although this also has been challenged. 4It is acknowledged that not all cases of asthma fit this paradigm-for example, some occupational causes of asthma do not appear to involve atopy-but these are regarded as interesting minor anomalies that do not threaten the dominant paradigm.In this review we assess the extent to which the development of asthma is attributable to atopy (we do not consider the separate issue of the extent to which the development of atopy itself is attributable to allergen exposure, although this is also the subject of debate 1 ).We start by considering definitions of asthma and atopy and then review evidence on their association in random population surveys.We do not intend to argue that atopy does not play an important role in the development of a significant proportion of asthma cases.However, our concern is that the proportion of asthma cases attributable to atopy may have been overestimated, and that other possible aetiological mechanisms and risk factors for asthma may therefore have been neglected.
A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma
Authors: A.C. Roy, S.R. Park, D. Cunningham, Y.K. Kang, Y. Chao, L.T. Chen, C. Rees, H.Y. Lim, J. Tabernero, F.J. Ramos, M. Kujundzic, M.B. Cardic, C.G. Yeh, A. de Gramont
Journal: Annals of Oncology (2013)
Assessment of tennis elbow using the Marcy Wedge-Pro.
Authors: R W Smith, R Mani, M I Cawley, W Englisch, P Eckenberger
Journal: British Journal of Sports Medicine (1993)

The Marcy Wedge-Pro (MWP), a device used in training by tennis players, was employed in the assessment of tennis elbow. The MWP was used to measure the ability of patients to perform wrist extension exercises, since pain resulting from this specific activity is a prominent symptom of the condition. The MWP results were compared with clinical measures and found to identify accurately patients who responded to treatment (P < 0.05). This study illustrates the potential of the MWP to assess tennis elbow quantitatively.
Study design supporting the effectiveness of inhaled extra-fine beclomethasone/formoterol at the level of small airways of asthmatics
Authors: Todor Popov, Daniela Petrova, Tanya Kralimarkova, Yavor Ivanov, Tsanya Popova, Tsvetanka Odzhahova, Yanislava Ilieva, Plamen Yakovliev, Tsvetelina Lazarova, Ognyan Georgiev, Marinka Peneva, Vladimir Hodzhev, Elena Hodzheva, Maria Staevska, Vasil Dimitrov
Journal: European Respiratory Journal (2013)

Background. We made an attempt to establish in what way does treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differ from other combined preparations of ICS and long acting beta-agonist (LABA).

Methods. This was real life clinical observation of asthmatics switched to I-EF-BDP/F (Foster, Chiesi Pharma, Italy) from dry powder inhalers of fluticasone/salmetrol and budesonide/formoterol. Effects of 8-weeks treatment were documented by spirometry and airway / systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos) and C-reactive protein (CRP).

Results. 59 patients completed the study (mean age 51 ± SD 12 years, 38 women). They did not show significant pre/post changes in the inflammatory indices (EBT, Eos and CRP). However, when we ranked them according to the pre/post treatment differences in forced vital capacity % predicted (FVC, a simple indicator of small airways involvement), the subjects above the 75th percentile (“top responders”, n=15), demonstrated significant drop in EBT \[oC\] (34.04±0.30 vs. 33.57±0.33, P=0.003) and Eos \[cells/μL\] (381.7±91.2 vs. 244.2±43.2, P=0.018). The pre/post EBT and CRP differences of the “top responders” significantly exceeded those of the patients below the 25th percentile of FVC: P=0.04 and 0.05 respectively.

Conclusion. Subjects demonstrating highest improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations had prominent decrease in the level of inflammation. As FVC is a simple indicator of small airway involvement, these results support the notion that I-EF-BDP/F may exert its effects in the small airway.
Tumor Growth and Tumor Radiosensitivity in Mice Given Myeloprotective Doses of Fibroblast Growth Factors
Authors: Ivan Ding, Kundi Huang, Matthew L. Snyder, John Cook, Lurong Zhang, Nancy Wersto, Paul Okunieff
Journal: JNCI Journal of the National Cancer Institute (1996)

Background: Radiation at doses high enough to cure cancer also frequently destroys normal tissue. Development of agents that protect normal tissue without also protecting diseased tissue has been difficult. In vivo radioprotection of bone marrow by acidic and basic fibroblast growth factors (FGF 1 and FGF 2 , respectively) has recently been demonstrated after whole-body irradiation of C3H/HeN mice.
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease
Authors: Maria Florencia Delgado, Silvina Coviello, A Clara Monsalvo, Guillermina A Melendi, Johanna Zea Hernandez, Juan P Batalle, Leandro Diaz, Alfonsina Trento, Herng-Yu Chang, Wayne Mitzner, Jeffrey Ravetch, José A Melero, Pablo M Irusta, Fernando P Polack
Journal: Nature Medicine (2008)
Extrahepatic cholestasis and liver stiffness by transient elastography
Authors: Ze‐Zhou Song
Journal: Hepatology (2009)

In their recent study, Millonig and colleagues1 concluded that extrahepatic cholestasis increases liver stiffness regardless of fibrosis and that once extrahepatic cholestasis is excluded, transient elastography (TE) is a valuable tool for assessing liver fibrosis in chronic liver diseases. The methods and interpretation of the results, however, raise several concerns. TE should be performed to evaluate disease progression in chronic liver diseases by liver stiffness measurement even if liver stiffness measurement is not a reliable instrument for detecting the presence of advanced fibrosis and cirrhosis in patients presenting with a clinical picture of acute hepatitis.2 Also, the time at which TE should be performed after the resolution of extrahepatic cholestasis for the evaluation of disease progression in chronic liver diseases is very important. In other words, it is very important to determine when liver stiffness values by TE correspond well to the histological degree of fibrosis ascertained by liver biopsy after the resolution of extrahepatic cholestasis. In the study by Millonig et al.,1 however, liver biopsy was not performed. Therefore, the aforementioned question needs to be further confirmed. It is well known that liver stiffness values in the general population are influenced independently by gender, body mass index, and metabolic syndrome and tend to be higher with age.3 In the study by Millonig and colleagues,1 decreases in liver stiffness after successful biliary drainage were different among the enrolled patients. Moreover, were there any relationships between the differences in the decreases in liver stiffness after successful biliary drainage and gender, body mass index, metabolic syndrome, and age? In other words, did the liver stiffness values from TE correspond well to the histological degree of fibrosis ascertained by liver biopsy after the resolution of extrahepatic cholestasis? This also needs to be further confirmed. Ze-Zhou Song M.S.*, * Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Performance of rapid tests for detection of HBsAg and anti-HBsAb in a large cohort, France
Authors: Julie Bottero, Anders Boyd, Joel Gozlan, Maud Lemoine, Fabrice Carrat, Anne Collignon, Nicolas Boo, Philippe Dhotte, Brigitte Varsat, Gérard Muller, Olivier Cha, Odile Picard, Jean Nau, Pauline Campa, Benjamin Silbermann, Marc Bary, Pierre-Marie Girard, Karine Lacombe
Journal: Journal of Hepatology (2012)
A deletion causing NF2 exon 9 skipping is associated with familial autosomal dominant intramedullary ependymoma
Authors: Ilyess Zemmoura, Patrick Vourc'h, Agathe Paubel, Béatrice Parfait, Joëlle Cohen, Frédéric Bilan, Alain Kitzis, Cécilia Rousselot, Fabrice Parker, Patrick François, Christian R. Andres
Journal: Neuro-Oncology (2013)

Intramedullary ependymomas are rare and benign tumors in the adult. Little is known about their physiopathology, but the implication of the NF2 gene is suspected because of their presence in a third of patients with type 2 neurofibromatosis (NF2), a disorder caused by mutation of the NF2 gene.We conducted a clinical and genetic study of a family in which 5 of 9 members suffered from intramedullary ependymoma. Karyotyping and CGH array analysis were performed on DNA from peripheral blood lymphocytes from affected participants. The NF2 gene sequences were then determined in DNA from 3 nonaffected and all 5 affected members of the family.Karyotype and CGH array findings were normal. Sequencing of NF2 revealed a heterozygous deletion, c.811-39_841del69bp, at the intron 8/exon 9 junction, in all affected members that was absent from all nonaffected members. RT-PCR analysis and sequencing revealed a novel NF2 transcript characterized by a skipping of exon 9 (75 bp). This deletion is predicted to result in a 25-amino acid deletion in the N-terminal FERM domain of neurofibromin 2. Modeling of this mutant domain suggests possible disorganization of the subdomain C.We report the first family with an NF2 mutation associated with intramedullary ependymomas without other features of NF2 syndrome. This mutation, which has not been described previously, may particularly affect the function of neurofibromin 2 in ependymocytes leading to the development of intramedullary WHO grade II ependymomas. We propose that sporadic intramedullary ependymomas should also be analyzed for this region of NF2 gene.
Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120
Authors: Ronald S. Veazey, Robin J. Shattock, Melissa Pope, J. Christian Kirijan, Jennifer Jones, Qinxue Hu, Tom Ketas, Preston A. Marx, Per Johan Klasse, Dennis R. Burton, John P. Moore
Journal: Nature Medicine (2003)
Down and almost out in Scotland: George Orwell, tuberculosis and getting streptomycin in 1948
Authors: H. Bastian
Journal: Journal of the Royal Society of Medicine (2006)

On Christmas Eve 1947, Eric Blair (pen-name, George Orwell) was admitted to Hairmyres Hospital near Glasgow.2 George Orwell (Figure 1) was a journalist and novelist, and the publication in 1945 of his political fable, Animal Farm,3 had made him famous. He was 44 years old, and tests at the hospital confirmed that he had infectious chronic tuberculosis in his lungs.4 Orwell has been described as ‘a representative of truth-telling, objectivity and verification’.5 As with other events in his life, he carefully analysed and documented his experience of care for his tuberculosis, including his time in a private sanitorium. Orwell had been given treatments that were common for tuberculosis in Britain at that time: ‘collapse therapy’ and other painful surgical procedures to keep the lung disabled to ‘rest’ it, vitamins, fresh air, and being confined to bed. The hospital staff confiscated his typewriter and told him to stop working6—but they didn’t seem to advise him to stop smoking! (Figure 2) Orwell’s work, a novel he would struggle to complete in the coming year—1948, was Orwell’s ‘last great obsession’.7 He twisted the numbers of that year to give the book one of the most famous titles and powerful symbols from the 20th century: Nineteen EightyFour,8 introducing Big Brother and words like ‘doublespeak’ to the international political and social landscape (Figure 3). Orwell was hopeful:
Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat
Authors: R De Giorgio
Journal: Gut (2001)

<h3>BACKGROUND</h3> In the rat, gastric distension elicits an intensity dependent pseudoaffective bradycardia mediated via capsaicin sensitive afferent and cholinergic efferent vagal pathways. Inflammation alters visceral perception although the mediators responsible have not been identified. In the nematode infected rat, there is a substantial increase in neuronal substance P (SP) content of the gut. <h3>AIMS</h3> To examine the effects of inflammation on perception of a noxious visceral stimulus and on SP and neurokinin 1 (NK-1) receptor immunoreactivity (IR) in visceral afferent pathways. <h3>METHODS</h3> Immunohistochemistry was performed on sections from the jejunum, dorsal root ganglia (DRG), and spinal cord (T1–L1) using SP and NK-1 rabbit polyclonal antibodies. In the DRG, the number of SP-IR or NK-1-IR neurones per section was visually quantified. The pseudoaffective cardiac reflex response to gastric stimulation was compared in control and<i>Trichinella spiralis </i>infected rats. <h3>RESULTS</h3> Intestinal inflammation induced a rightward shift in the intensity dependent bradycardic response to gastric distension. This was associated with a marked increase in SP-IR not only in the gut wall but also in the DRG and dorsal horn of the spine. In contrast, NK-1-IR was not increased in the gut wall. Moreover, inflammation evoked a decrease in NK-1-IR in the dorsal horn. No NK-1-IR was identified in the DRG of either control or infected animals. <h3>CONCLUSIONS</h3> Intestinal inflammation modulates the capsaicin sensitive pseudoaffective autonomic response to gastric distension, increases SP-IR in afferent pathways, and downregulates dorsal horn NK-1-IR. As the pseudoaffective response is capsaicin sensitive, the rightward shift of the response is likely the consequence of the decrease in NK-1 receptors in the sensory pathways.
Adaptive Evolution of the Water Stress-Induced Gene Asr2 in Lycopersicon Species Dwelling in Arid Habitats
Authors: N. Frankel
Journal: Molecular Biology and Evolution (2003)

The Asr2 gene encodes a putative transcription factor that is up-regulated in leaves and roots of tomato plants exposed to water-deficit stress. This gene was first cloned and characterized in a cultivar of commercial tomato (Lycopersicon esculentum cv. Ailsa Craig). In this work, we report the complete coding sequences of the orthologous Asr2 genes in six wild tomato lineages: L. hirsutum, L. cheesmanii, L. esculentum v. cerasiforme, L. chilense, L. peruvianum v. humifusum and L. peruvianum f. glandulosum. Estimates of the Ka/Ks ratio (omega) in pairwise comparisons within the genus Lycopersicon were equal or greater than 1 (a signature of adaptive evolution) when involving L. chilense and L. peruvianum v. humifusum. Interestingly, these two species are distinct from the others in their adaptation to dry habitats. We also mapped the detected substitutions onto a phylogenetic tree of the genus Lycopersicon. Remarkably, there are two and three amino acid substitutions, which contrast with the absence of synonymous substitutions along the terminal branches leading to L. chilense and L. peruvianum v. humifusum, respectively. Likelihood ratio tests confirmed that omega values in the branches leading to these species are significantly different from the remaining branches of the tree. Moreover, inferred changes in the branches leading to these species that inhabit dry areas are nonconservative and may be associated with dramatic alterations in ASR2 protein conformation. In this work, we demonstrate accelerated rates of amino acid substitutions in the Asr2 gene of tomato lineages living in dry habitats, thus giving support to the hypothesis of adaptive Darwinian evolution.