tbuckley/cabot-search huggingface dataset:
Does central nervous system plasticity contribute to hyperalgesia?
Authors: Corey L. Cleland, G. F. Gebhart
Journal: Behavioral and Brain Sciences (1997)

Hyperalgesia can arise from peripheral sensitization, on-going peripheral activation, and central plasticity. In the target article, coderre &amp; katz argue that all three mechanisms contribute to hyperalgesia. In contrast, we believe that existing experimental evidence suggests that central plasticity plays only an insignificant role in most experimental models and clinical presentations of hyperalgesia induced by tissue injury or chemical activation of sensory receptors.
SAGITTAL SPINAL CURVATURES IN MAXIMAL TRUNK FLEXION OF YOUNG FEMALE DANCERS
Authors: F Esparza-Ros, R Vaquero-Cristóbal, F Alacid, E Martínez-Ruiz, PA López-Miñarro
Journal: British Journal of Sports Medicine (2014)

Background Kyphotic postures in both thoracic and lumbar curves have been associated to increased shear and compressive forces in the intervertebral joints. Hamstring extensibility influences pelvic, thoracic and lumbar curvatures when trunk bending movements are performed. Some studies have found higher hamstring muscle extensibility in dancers than other athletes. Objective To classify sagittal thoracic and lumbar curves when performed a maximum trunk flexion with knees extended (sit-and-reach test) in female dancers with high hamstring extensibility. Design Descriptive study. Setting Dance Conservatory professional. The sample included dance students of Professional education teaching. Participants 86 female dancers (mean±SD, age: 15.18±2.62 years-old) with a straight leg raise test greater than 90° were recruited for this study. Interventions Not applicable. Main outcome measurements Thoracic and lumbar curvatures were measured when maximal trunk flexion with knees extended (sit-and-reach test) was reached using a Spinal Mouse ® . Thoracic values were classificated in three categories: slight (&lt;45°), mild (45–60°) or high (&gt;60°) kyphotic curve. Lumbar values were also classificated in three categories: slight (&lt;23°), mild (23–31°) or high (&gt;31°) kyphotic curve. Results Most dancers showed slight (43.02%) and mild (33.72%) thoracic curvature whereas the frequency of high thoracic kyphosis was 23.26%. Thirty-seven dancers showed thoracic angles between -5 and 44° (slight group) (mean value: 30.35±11.42°). The mean thoracic kyphosis of mild group was 51.55±4.80°. The high group showed values between 61 and 79° (mean value: 66.95±5.43°). With regards to the lumbar curvature, a large amount of the sample showed high (46.51%) and mild (37.20%) kyphotic curves. Conclusions Dance training is associated to increased lumbar kyphosis when maximum trunk flexion with knees extended is performed. Greater intervertebral bending of the lumbar spine in dancers could be associated to their high hamstring extensibility.
Modification of Cysteine Residues In Vitro and In Vivo Affects the Immunogenicity and Antigenicity of Major Histocompatibility Complex Class I–restricted Viral Determinants
Authors: Weisan Chen, Jonathan W. Yewdell, Rodney L. Levine, Jack R. Bennink
Journal: The Journal of Experimental Medicine (1999)

In studying the subdominant status of two cysteine-containing influenza virus nuclear protein (NP) determinants (NP39–47 and NP218–226) restricted by H-2Kd, we found that the antigenicity of synthetic peptides was enhanced 10–100-fold by treatment with reducing agents, despite the fact that the affinity for Kd was not enhanced. Reducing agents also markedly enhanced the immunogenicity of cysteine-containing peptides, as measured by propagation of long-term T cell lines in vitro. Similar enhancing effects were obtained by substituting cysteine with alanine or serine in the synthetic peptides, demonstrating that sulfhydryl modification of cysteine is responsible for the impaired antigenicity and immunogenicity of NP39–47 and NP218–226. We found similar effects for two widely studied, cysteine-containing peptides from lymphocytic choriomeningitis virus. The major modifications of cysteine-containing synthetic peptides are cysteinylation and dimerization occurring through cysteine residues. We demonstrate that both of these modifications occur in cells synthesizing a cytosolic NP218–226 minigene product and, further, that T cells specific for cysteinylated NP218–226 are induced by influenza virus infection in mice, demonstrating that this modification occurs in vivo. These findings demonstrate that posttranslational modifications affect the immunogenicity and antigenicity of cysteine-containing viral peptides and that this must be considered in studying the status of such peptides in immunodominance hierarchies.
A Hybrid Hydrogel Biomaterial by Nanogel Engineering: Bottom‐Up Design with Nanogel and Liposome Building Blocks to Develop a Multidrug Delivery System
Authors: Yurina Sekine, Yuki Moritani, Tomoko Ikeda‐Fukazawa, Yoshihiro Sasaki, Kazunari Akiyoshi
Journal: Advanced Healthcare Materials (2012)

Abstract New hybrid poly(ethylene glycol) (PEG) hydrogels crosslinked with both nanogels and nanogel‐coated liposome complexes are obtained by Michael addition of the acryloyl group of a cholesterol‐bearing pullulan (CHP) nanogel to the thiol group of pentaerythritol tetra(mercaptoethyl) polyoxyethylene. The nanogel‐coated liposome complex is stably retained after gelation and the complexes are well dispersed in the hybrid gel. Microrheological measurements show that the strength and gelation time of the hybrid hydrogel can be controlled by changing the liposome:nanogel ratio. The hydrogel is gradually degraded by hydrolysis under physiological conditions. In this process, the nanogel is released first, followed by the nanogel‐coated liposomes. Hybrid hydrogels that can incorporate various molecules into the nanogel and liposomes, and release them in a two‐step controllable manner, represent a new functional scaffold capable of delivering multiple drugs, proteins or DNA.
HEXIM1 Regulates 17β-Estradiol/Estrogen Receptor-α–Mediated Expression of Cyclin D1 in Mammary Cells via Modulation of P-TEFb
Authors: Ndiya Ogba, Laura J. Chaplin, Yong Qiu Doughman, Koh Fujinaga, Monica M. Montano
Journal: Cancer Research (2008)

Estrogen receptor alpha (ERalpha) plays a key role in mammary gland development and is implicated in breast cancer through the transcriptional regulation of genes linked to proliferation and apoptosis. We previously reported that hexamethylene bisacetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound ERalpha and bridges a functional interaction between ERalpha and positive transcription elongation factor b (P-TEFb). To examine the consequences of a functional HEXIM1-ERalpha-P-TEFb interaction in vivo, we generated MMTV/HEXIM1 mice that exhibit mammary epithelial-specific and doxycycline-inducible expression of HEXIM1. Increased HEXIM1 expression in the mammary gland decreased estrogen-driven ductal morphogenesis and inhibited the expression of cyclin D1 and serine 2 phosphorylated RNA polymerase II (S2P RNAP II). In addition, increased HEXIM1 expression in MCF-7 cells led to a decrease in estrogen-induced cyclin D1 expression, whereas down-regulation of HEXIM1 expression led to an enhancement of estrogen-induced cyclin D1 expression. Studies on the mechanism of HEXIM1 regulation on estrogen action indicated a decrease in estrogen-stimulated recruitment of ERalpha, P-TEFb, and S2P RNAP II to promoter and coding regions of ERalpha-responsive genes pS2 and CCND1 with increased HEXIM1 expression in MCF-7 cells. Notably, increased HEXIM1 expression decreased only estrogen-induced P-TEFb activity. Whereas there have been previous reports on HEXIM1 inhibition of P-TEFb activity, our studies add a new dimension by showing that E(2)/ER is an important regulator of the HEXIM1/P-TEFb functional unit in breast cells. Together, these studies provide novel insight into the role of HEXIM1 and ERalpha in mammary epithelial cell function.
Modeling RAS Phenotype in Colorectal Cancer Uncovers Novel Molecular Traits of RAS Dependency and Improves Prediction of Response to Targeted Agents in Patients
Authors: Justin Guinney, Charles Ferté, Jonathan Dry, Robert McEwen, Gilles Manceau, KJ Kao, Kai-Ming Chang, Claus Bendtsen, Kevin Hudson, Erich Huang, Brian Dougherty, Michel Ducreux, Jean-Charles Soria, Stephen Friend, Jonathan Derry, Pierre Laurent-Puig
Journal: Clinical Cancer Research (2013)

Abstract Purpose: KRAS wild-type status is an imperfect predictor of sensitivity to anti-EGF receptor (EGFR) monoclonal antibodies in colorectal cancer, motivating efforts to identify novel molecular aberrations driving RAS. This study aimed to build a quantitative readout of RAS pathway activity to (i) uncover molecular surrogates of RAS activity specific to colorectal cancer, (ii) improve the prediction of cetuximab response in patients, and (iii) suggest new treatment strategies. Experimental Design: A model of RAS pathway activity was trained in a large colorectal cancer dataset and validated in three independent colorectal cancer patient datasets. Novel molecular traits were inferred from The Cancer Genome Atlas colorectal cancer data. The ability of the RAS model to predict resistance to cetuximab was tested in mouse xenografts and three independent patient cohorts. Drug sensitivity correlations between our model and large cell line compendiums were performed. Results: The performance of the RAS model was remarkably robust across three validation datasets. (i) Our model confirmed the heterogeneity of the RAS phenotype in KRAS wild-type patients, and suggests novel molecular traits driving its phenotype (e.g., MED12 loss, FBXW7 mutation, MAP2K4 mutation). (ii) It improved the prediction of response and progression-free survival (HR, 2.0; P &amp;lt; 0.01) to cetuximab compared with KRAS mutation (xenograft and patient cohorts). (iii) Our model consistently predicted sensitivity to MAP–ERK kinase (MEK) inhibitors (P &amp;lt; 0.01) in two cell panel screens. Conclusions: Modeling the RAS phenotype in colorectal cancer allows for the robust interrogation of RAS pathway activity across cell lines, xenografts, and patient cohorts. It demonstrates clinical utility in predicting response to anti-EGFR agents and MEK inhibitors. Clin Cancer Res; 20(1); 265–72. ©2013 AACR.
'Dottyville'--Craiglockhart War Hospital and shell-shock treatment in the First World War
Authors: T. E F Webb
Journal: Journal of the Royal Society of Medicine (2006)

‘... THAT MECCA OF PSYCHO-NEUROSES...’1

Craiglockhart is perhaps the most famous shell-shock hospital. It was set up to deal with the epidemic of psychological casualties created in the muddy trenches of the First World War; and, in particular, with the huge increase of casualties following the battle of the Somme in 1916. The hospital's fame is unsurprising in that two of the finest poets of a war over-flowing with poetic voices were treated there—Wilfred Owen and Siegfried Sassoon. It was Sassoon who nicknamed the place ‘Dottyville’ in a letter of 1917.2

The hospital's literary importance has been established by Sassoon's memoirs, a stage play, the fine novels of Pat Barker's Regeneration trilogy and a film version of the first of these novels.3 Yet its role has not always been accurately portrayed. Much of the emphasis has been on an unrepresentative doctor-patient relationship between Dr William Rivers and Siegfried Sassoon about which Sassoon wrote much after the war. The hospital has been conscripted by these misrepresentations into a simplistic view of shell-shock treatments delineated by rank: physical torture and humiliation for the other ranks (who were not treated at Craiglockhart), and a subtle reprogramming taking the form of friendly chats with avuncular doctors over tea and scones for the officer classes (who were).

Craiglockhart also has an important place in the development of British neuropsychiatry. The concept of a psychological stressor resulting in physical symptoms was still a relatively novel one in this period; the necessities of coping with an epidemic of psychological casualties in the context of the war allowed some fundamental aspects of Freud's ideas regarding repression and the unconscious to gain greater acceptance and currency in the medical profession. In addition, the previously presented chronology of the hospital appears to be inaccurate when the contemporary sources are examined together. The chronology offered here for the first time solves the glaring inconsistencies of the previous accounts.4 It has been possible to examine the hospital's admission and discharge registers and assess the destination of patients treated there as well as to systematically examine the accounts of the patients and staff to gain a clearer insight into their views and experiences, neither of which has been done before.
P258 Role of 7-day and 14-day courses of oral prednisolone treatment in acute exacerbation of COPD
Authors: S. M. A. Al Mamun, S. Rahman
Journal: Thorax (2011)

<h3>Purpose</h3> The purpose of this study was to compare the efficacy of 7-day and 14-day courses of oral prednisolone treatment in patients with acute exacerbation of COPD with FEV<sub>1</sub>&lt;50% predicted. <h3>Methods</h3> It was a prospective randomised, single blind study in a tertiary care centre, the study patients were included and randomised into two groups: 7-day group received oral prednisolone 30 mg/day for 7 days, and 14-day group was administered the same dosage of oral prednisolone for 14 days. There was no significant difference between the groups for age, smoking pack years, symptoms of COPD in years, no. of previous exacerbations, blood eosinophilia, baseline FEV<sub>1</sub>, and FVC levels. One patient from 7-day group developed pneumothorax and one from 14-day group died of acute Myocardial Infarction. <h3>Results</h3> Both groups showed significant improvements of FEV<sub>1</sub> and FVC on D-1, D-3, D-5, D-7, D-10 and Day-14 from the baseline (7-day group, p=0.0001, 0.0001, 0.008, 0.009, 0.008, 0.011and 14-day group, p=0.000, 0.000, 0.000, 0.000, 0.000, 0.000) and the improvement of FVC is also significant in both the groups, but there was no significant difference of improvement between the two groups on day-7 and day-14 (p=0.100, 0.079). There was also significant improvement of symptom score from baseline on day-7 and day-14, but no significant difference of improvement between two groups. <h3>Conclusion</h3> In acute exacerbation of COPD there is no difference between 7-day and 14-day courses of treatment with oral prednisolone. The peak of FEV<sub>1</sub> and FVC in 7-day group on day-10 where corticosteroid was already stopped on day-7, (peak in 14-day group was on day-7) might be due to some other factor/factors responsible which would be cleared by further study. <h3>Clinical implications</h3> There was no difference between 7-day and 14-day courses of prednisolone treatment, so, 7-day might be the shortest effective course of steroid treatment in acute exacerbation of COPD to avoid the burden of cost and side effects.
Control of nocturnal hypoventilation by nasal intermittent positive pressure ventilation.
Authors: N Carroll, M A Branthwaite
Journal: Thorax (1988)

Ten patients with respiratory failure and nocturnal hypoventilation were treated for three to nine months by nasal intermittent positive pressure ventilation. Four patients had chronic obstructive lung disease (median FEV1 19% predicted) and six restrictive chest wall disorders (median FVC 25% predicted); eight of the patients also had cardiac failure. The median daytime arterial oxygen tension, measured before and after at least three months' treatment, increased from 6.2 (range 5.4-9.6) to 9.1 (7.1-9.8) kPa in those with restrictive disease (p less than 0.05), and from 6.0 (5.7-6.5) to 7.1 (6.3-7.7) kPa in the four with airflow limitation (NS). Median values for arterial carbon dioxide tension over the same time fell from 8.2 (range 6.7-9.8) to 6.5 (6.0-6.9) kPa in the group with restrictive disease (p less than 0.05) and from 8.2 (7.0-9.2) to 7.1 (4.9-7.7) kPa in those with airflow limitation (p less than 0.02). Total sleep time while patients were using nasal positive pressure ventilation varied from 155 to 379 (median 341) minutes, and included 4-26% rapid eye movement sleep (median 14%). The percentage of monitored time during the night in which the arterial oxygen saturation was less than 80% fell from a median (range) of 96 (3-100) to 4 (0-9) in the six patients with restrictive disease and from 100 (98-100) to 40 (2-51) in those with airflow limitation. There were no changes in spirometric values but exercise tolerance improved in all patients. The technique may prove an acceptable alternative to long term domiciliary oxygen therapy in selected patients.
Bone Density, Body Composition, and Inflammatory Status in Cystic Fibrosis
Authors: ALINA A. IONESCU, LISETTE S. NIXON, WILLIAM D. EVANS, MICHAEL D. STONE, VANESSA LEWIS-JENKINS, KEN CHATHAM, DENNIS J. SHALE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α ), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores ⩽ 2.5 SD (n = 13) or ⩽ 1 SD (n = 7) at least at one site. They had increased bone collagen breakdown, greatest in those with a reduced FFM. BMD was related to FEV1 (r = 0.44), IL-6 (r = − 0.60), and TNF- α -soluble receptors (r = − 0.42, r = − 0.50). Patients with a low FFM had greater concentrations of IL-6, which suppressed less after antibiotic treatment than in those with a normal FFM. Those with a low FFM were more catabolic and less active than those with a normal FFM. The association between altered body composition, catabolic status, and circulating inflammatory mediators suggests that chronic pulmonary infection in adults with CF may be a contributory factor in the long-term complications of low weight and bone disease.
Loss of <i>Phosphatase and Tensin Homologue Deleted on Chromosome 10</i> Engages ErbB3 and Insulin-Like Growth Factor-I Receptor Signaling to Promote Antiestrogen Resistance in Breast Cancer
Authors: Todd W. Miller, Marianela Pérez-Torres, Archana Narasanna, Marta Guix, Olle Stål, Gizeh Pérez-Tenorio, Ana M. Gonzalez-Angulo, Bryan T. Hennessy, Gordon B. Mills, J. Phillip Kennedy, Craig W. Lindsley, Carlos L. Arteaga
Journal: Cancer Research (2009)

Knockdown of the tumor suppressor phosphatase Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased phosphatidylinositol-3 kinase (PI3K) and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. PTEN knockdown induced the up-regulation of ER transcriptional activity in MCF-7 cells but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. Tamoxifen and fulvestrant treatment inhibited estradiol-induced ER transcriptional activity in all shPTEN cell lines but did not abrogate the increased cell proliferation induced by PTEN knockdown. PTEN knockdown increased basal and ligand-induced activation of the insulin-like growth factor-I (IGF-I) and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-I receptor (IGF-IR) effector insulin receptor substrate-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine-phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Inhibition of IGF-IR and/or ErbB2-mediated activation of ErbB3 with tyrosine kinase inhibitors restored hormone dependence and the growth inhibitory effect of tamoxifen and fulvestrant on shPTEN cells, suggesting that cotargeting both ER and receptor tyrosine kinase pathways holds promise for the treatment of patients with ER+, PTEN-deficient breast cancers.
Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node
Authors: Eileen T. Samy, Lucy A. Parker, Colin P. Sharp, Kenneth S.K. Tung
Journal: The Journal of Experimental Medicine (2005)

This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-γ production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.