tbuckley/cabot-search huggingface dataset:
Enhanced MET Translation and Signaling Sustains K-Ras–Driven Proliferation under Anchorage-Independent Growth Conditions
Authors: Saori Fujita-Sato, Jacqueline Galeas, Morgan Truitt, Cameron Pitt, Anatoly Urisman, Sourav Bandyopadhyay, Davide Ruggero, Frank McCormick
Journal: Cancer Research (2015)

Abstract Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to chemotherapeutic drugs as well as molecular targeting agents. Although numerous approaches are ongoing to find effective ways to treat these tumors, there are still no effective therapies for K-Ras mutant cancer patients. Here we report that K-Ras mutant cancers are more dependent on K-Ras in anchorage-independent culture conditions than in monolayer culture conditions. In seeking to determine mechanisms that contribute to the K-Ras dependency in anchorage-independent culture conditions, we discovered the involvement of Met in K-Ras–dependent, anchorage-independent cell growth. The Met signaling pathway is enhanced and plays an indispensable role in anchorage-independent growth even in cells in which Met is not amplified. Indeed, Met expression is elevated under anchorage-independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase (MEK)-dependent manner. Remarkably, in spite of a global downregulation of mRNA translation during anchorage-independent growth, we find that Met mRNA translation is specifically enhanced under these conditions. Importantly, ectopic expression of an active Met mutant rescues K-Ras ablation-derived growth suppression, indicating that K-Ras–mediated Met expression drives “K-Ras addiction” in anchorage-independent conditions. Our results indicate that enhanced Met expression and signaling is essential for anchorage-independent growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors of Met could be effective for K-Ras mutant tumor patients. Cancer Res; 75(14); 2851–62. ©2015 AACR.
Maximal ventilatory pressure and pulmonary function in subjects with non-cystic fibrosis bronchiectasis
Authors: Newton Santos de Faria Júnior, Renata Kelly Palma, Israel dos Reis dos Santos, Jéssica Julioti Urbano, Ismael Souza Dias, Angela Honda Souza, Oliver Augusto Nascimento, José Roberto Jardim, Luis Vicente Franco Oliveira, Roberto Stirbulov
Journal: European Respiratory Journal (2014)

Introduction: The assessment of pulmonary function and the maximal ventilatory pressures have been of great clinical importance, besides having great potential for the diagnosis and prognosis of lung diseases. Due to airflow obstruction, irreversible dilatation of the bronchi and bronchioles, and the presence of secretion individuals with bronchiectasis (BCTS) may show changes in their respiratory muscles and lung capacity, leading to impact on your quality of life health related. Objective: To assess the pulmonary function and the maximum ventilatory pressure in subjects with BCTS. Method: This is an observational and cross-sectional study that assessed 21 patients with a previous diagnosis of BCTS, at Respiratory Physiology laboratory of Nove de Julho University (UNINOVE) in the city of Sao Paulo- Brazil. The evaluation consisted of medical history, vital signs, anthropometry, spirometry and manovacuometry. Results: The mean age was 51.57±15.11 years, (57.1% female) and body mass index of 23.93 ± 3.75 kg/m2. There was a predominance of obstructive lung disease (52.4%) and reductions in the mean spirometric values of predicted (FVC, FEV1 and FEV1/FVC were 2.45 ± 0.87, 1.63 ± 0.76 and 66.49 ± 15.26 respectively). The mean values of maximal inspiratory pressures for females were 70.16 ± 26.60 and 95.55 ± 22.92 for males. The maximum expiratory pressures were 63.66 ± 24.34 and 105.11 ± 23.85 respectively for females and males. Conclusion: Patients with BCTS presented a predominance of obstructive lung disease, reductions in spirometric values and maximal ventilatory pressures, either with regard to gender or etiology of BCTS compared with Brazilian population.
Response to: ‘Belimumab and the measurement of fatigue’ by Mazzoni
Authors: V Strand, R A Levy, R Cervera, M Petri
Journal: Annals of the Rheumatic Diseases (2015)

We agree that fatigue is a common and important symptom of patients with active systemic lupus erythematosus (SLE), and that it is multidimensional, as has been elegantly described in patients with rheumatoid arthritis.1 In fact, randomised controlled trials in SLE have assessed fatigue, as early as the prasterone dehydroepiandrosterone (DHEA) studies (published in 2002–2004) that employed the (Krupp) Fatigue Severity Scale (FSS), developed …
Attention in Young Children of Psychotic Mothers
Authors: HENRY GRUNEBAUM, JUSTIN L. WEISS, DAVID GALLANT, BERTRAM J. COHLER
Journal: American Journal of Psychiatry (1974)

The authors report findings from an investigation of cognitive and attentional development in 53 children of psychotic mothers and their matched controls demonstrating the presence of developmental lag in the high-risk children and suggesting the existence of relationships between parental and child measures of these functions. The children of schizophrenic mothers appear to be especially vulnerable to attentional deficit.
Sliding Hip Screws and Medial Displacement Osteotomy
Authors: D Nunn
Journal: Journal of the Royal Society of Medicine (1988)

The case notes and radiographs of 108 patients who had undergone compression screw fixation of trochanteric fractures of the femur were reviewed. Forty-seven patients had unstable comminuted fractures, and 20 of these had medial displacement osteotomies performed. In 40% of this group the operation was not a success in terms of extrusion of the screw through the femoral head, compared with 20% for the whole series of 108 patients. A number of parameters were studied in the search for a cause for the failure, and there was a correlation with a superior position of the screw initially, and a low serum albumin. Although the proximal fragment abutted the plate at the time of operation, the medial cortices of the proximal and distal fragments were often not in apposition, allowing the fracture to collapse into varus with resultant extrusion. Unless a stable configuration is achieved at the time of operation, reliance on the sliding component of these implants to allow for collapse at the fracture site will not necessarily produce this stability, and failure will ensue.
Impact of traffic-related pollution on respiratory function in children living in London's low emission zone: A sequential cross sectional study
Authors: Chris Griffiths, Ian Mudway, Helen Wood, Isobel Dundas, Louise Cross, Nadine Marlin, Jeenath Jamaludin, Stephen Bremner, Robert Walton, Andrew Grieve, Jonathan Grigg, Chinedu Nwokoro, Rossa Brugha, Sean Beevers, Seif Shaheen, Tak Lee, Frank Kelly
Journal: European Respiratory Journal (2013)

Background  Low emission zones (LEZ) are a new approach to improving air quality and respiratory health in cities, but their benefits have not been robustly evaluated. We examined the impact of the initial phases of London’s LEZ on the health of children aged 8-9 years, living in east London, where 83% of the sampled population live in areas failing to meet the EU annual limit for NO2 (40 mg/m3).  Methods  From 2008 we prospectively assessed respiratory health of sequential yearly cross-sectional samples of children at 23 east London schools. We examined relationships between modelled traffic derived pollutant exposures (NOx, NO 2 , PM 2.5,  PM 10 ) and lung function (FEV1, FVC). Chronic annual exposures were assigned at residential address level, with adjustments for periods spent at home and school. Acute exposures were assessed by scaling annual mean concentrations by averaged background and roadside measurements for each pollutant for sub-acute (7 days) and acute (24 hr) periods immediately prior to school visits.  Findings  Technically acceptable post-bronchodilator lung function data was obtained for 887 children. We found no evidence of year-on-year improvements in lung function in the three years following LEZ introduction. Higher annual exposures for all four pollutants across the first three years of the LEZ were associated with significantly reduced FVC, with no influence of acute and sub-acute exposures.  Conclusions  We found no improvement in children9s respiratory health in the initial years of London9s LEZ. We observed evidence of reduced lung volume related to long term exposure to traffic pollutants consistent with impaired lung growth.
Uric Acid Induces NADPH Oxidase–Independent Neutrophil Extracellular Trap Formation
Authors: Yasuyuki Arai, Yoko Nishinaka, Toshiyuki Arai, Kiyomi Mizugishi, Souichi Adachi, Akifumi Takaori-Kondo, Kouhei Yamashita
Journal: Blood (2013)
Prolonged sirolimus therapy in advanced pulmonary lymphangioleiomyomatosis; a multicenter French experience
Authors: Carine Gomez, Camille Taillé, Romain Lazor, Bruno Crestani, Vincent Cottin, Martine Reynaud-Gaubert
Journal: European Respiratory Journal (2012)

Introduction:  Lymphangioleiomyomatosis (LAM) and tuberous sclerosis (TS) are orphan diseases associated with TSC1/2 gene mutation and dysregulated mTOR/Akt signaling. Usefulness of the mTOR inhibitor sirolimus (SIR) in slowing the decline of lung function in LAM has been shown.   Aims and Objectives:  Evaluate efficacy and safety of prolonged treatment with Sir in LAM patients.   Methods:  An observational retrospective study of 14 patients with LAM and declining lung function treated with Sir and follow-up over 18 months of SIR.   Results:  All patients included in the study were female with sporadic LAM (n=9) or TSC-LAM (n=5). Six patients had chylous effusion and 3 had pulmonary hypertension. The median dosage of SIR was 2.5 mg/d and the blood T0 was 5.5 mg/mL (1.8-10). Clinical and functional improvement from baseline was observed in all after 6 months of SIR therapy. At M18 and M24, the functional benefit remained for all except one, 5 of the 6 patients with chylous effusion experienced complete resolution of this condition and pulmonary hemodynamic normalized in two. Progression of the disease after routine discontinuation of SIR after 2 years in 3 patients encouraged rechallenge with SIR, with again restoration of disease control. Tolerance of SIR was good in 12 patients, and therapy was stopped for moderate adverse events in 2 cases but restarted at lower dosage in one without complication.   Conclusion:  This study demonstrates that mTOR inhibition with SIR is useful in advanced LAM. Decline in lung function was observed after discontinuation of SIR with benefit of subsequent rechallenge in uncontrolled disease. Therapeutic scheme of SIR over time in LAM should be defined.
Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study.
Authors: H Raybaud-Diogène, A Fortin, R Morency, J Roy, R A Monteil, B Têtu
Journal: Journal of Clinical Oncology (1997)

PURPOSE The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs. PATIENTS AND METHODS p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables. RESULTS Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3.78 for not being controlled by radiotherapy compared with patients with p53-negative tumors. For tumors with a high growth fraction (ki-67 &gt; 20%) the RR was 0.25 compared with tumors with a low growth fraction (ki-67 &lt; 20%). When p53 expression and cell proliferation were considered simultaneously in a Cox model, the association with resistance to radiation was significant (P = .000004). The RR for resistance with one (p53 staining or ki-67 &lt; 20%) or two (p53 staining and ki-67 &lt; 20%) unfavorable markers was, respectively, 3.8 and 14.87. CONCLUSION Patients whose tumor expressed p53 with low growth fraction (ki-67 &lt; 20%) had a strong probability not to respond to radiation therapy. Similarly, absence of p53 expression with a high cell proliferation predicted an excellent outcome after radiotherapy even for patients with advanced disease. Prediction of the outcome of radiotherapy would eventually facilitate the early choice of an adequate treatment.
Dissemination of blaVIM in Greece at the peak of the epidemic of 2005–2006: clonal expansion of Klebsiella pneumoniae clonal complex 147
Authors: C.M. Hasan, A. Turlej-Rogacka, A.C. Vatopoulos, P. Giakkoupi, M. Maâtallah, C.G. Giske
Journal: Clinical Microbiology and Infection (2013)
Exposure to gas, dust and fumes increases the risk of mite sensitisation and asthma
Authors: Anders Bjerg, Linda Ekerljung, Stig Hagstad, Sigrid Sjölander, Magnus Borres, Jan Lötvall, Bo Lundbäck
Journal: European Respiratory Journal (2014)

Background: Allergic sensitisation is a major risk factor for asthma in adults. In Sweden, pollens and furry animals are the main sensitisers, while mites play a minor role and often exists as co-sensitisation.  Aim: To study risk factors for mite sensitisation in Swedish adults.  Methods: Out of 18072 participants in the West Sweden Asthma Study, a random sample of 1472 aged 16-60 y were invited to skin prick testing (SPT) 2009-2012. SPTs covered 11 aeroallergens, including the mites D. pteronyssinus and D. farinae. Complete SPTs were performed in 788 subjects (58% women).  Results: The prevalence of any mite sensitisation was 12.6%, 11.3% to D. pteronyssinus and 9.6% to D. farinae. Physician-diagnosed asthma was seen in 12.1% and current wheeze in 23.6%. Sensitisation to pollens, animals and mites showed similar risk factor patterns, however mite sensitisation was also associated with work exposure to gas, dust and fumes (GDF), OR 2.0 (1.2-3.3) and low birth weight (  Discussion: In this random sample of Swedish adults GDF and LBW were associated with sensitisation to mites, but not pollens or animals. GDF-associated respiratory epithelial damage and/or immunomodulatory mechanisms may contribute to mite sensitisation. The data suggest that the known association of GDF with respiratory symptoms occurs predominantly in mite-sensitised subjects.
Natural Killer Inhibitory Substance Produced by the Peritoneal Cells of Patients With Ovarian Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A K Lichtenstein, J Berek, J Zighelboim
Journal: JNCI Journal of the National Cancer Institute (1985)

Peritoneal cells obtained from 8 patients with minimal residual ovarian cancer produced a substance during in vitro culture that markedly inhibited the expression of natural killer (NK) cell-mediated lysis. Its molecular weight was less than 2,000, the same size as the NK-inhibiting substance (NK-IS), a similar NK-suppressive molecule produced by the peritoneal cells of rats. Human NK-IS suppressed the expression of antibody-dependent cell cytotoxicity as well as NK lysis, but it had no effect on erythrocyte-rosette formation and was not cytotoxic to peripheral blood lymphocytes or cell fractions enriched for large granular lymphocytes. NK-IS inhibited lysis mediated by interferon-activated lymphocytes and completely prevented NK activation when used in a preincubation. During intraperitoneal immunotherapy with Corynebacterium parvum, an agent that can activate peritoneal cytotoxic effectors, the production of NK-IS by peritoneal cells decreased considerably. Human peritoneal cells produce an NK-IS similar to the peritoneal cells of rats, and this material may create an environment within the peritoneal cavity that is permissive to the growth of NK-sensitive tumor cells.
The genetics of renal tumors in end-stage renal failure differs from those occurring in the general population.
Authors: J Chudek, J Herbers, M Wilhelm, C Kenck, P Bugert, E Ritz, F Waldman, G Kovacs
Journal: Journal of the American Society of Nephrology (1998)

The genetics of renal cell tumors (RCT), which occur at a high frequency in patients with end-stage renal failure (ESRF), is not yet known. Using a fluorescence microsatellite assay and comparative genomic hybridization, 18 renal tumors obtained from nine patients with ESRF were analyzed for genetic alterations, which are known to be characteristic of common nonpapillary and papillary RCT in the general population. Deletion of chromosome 3p was detected in six nonpapillary tumors, whereas trisomies of 7 and 17 or 3, 8, and 16 were seen in four of 18 tumors. No alterations were found in four tumors, and another four tumors had unspecific changes. The fragile histidine triad (FHIT) gene is localized at the most common fragile site at chromosome 3p14.2. The FHIT and the p53 tumor suppressor gene are targets of different environmental agents. Because both toxic effect and genomic instability are implicated in the development of renal cysts in ESRF, the alteration of both genes in tumor cells was analyzed. No abnormal expression of the FHIT gene or mutation of the p53 gene were found. This study suggests that the genetics and also the morphology of some of the ESRF RCT differ from those known for RCT in the general population.
Human ezrin-moesin-radixin proteins modulate hepatitis C virus infection
Authors: Terence N. Bukong, Karen Kodys, Gyongyi Szabo
Journal: Hepatology (2013)

Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, real-time quantitative polymerase chain reaction, western blot, and fluorescent microscopy analysis, we found that proteins of the EMR family differentially regulate HCV infection in the J6/JFH-1/Huh7.5 cell system. Moesin and radixin, but not ezrin, expression were significantly decreased in chronic HCV J6/JFH-1-infected Huh7.5 cells and HCV-infected patient liver biopsies compared to controls. The decreases in moesin and radixin in HCV J6/JFH-1-infected Huh7.5 cells were associated with a significant increase in stable microtubules. Ezrin knockdown inhibited immediate postentry events in HCV infection. Overexpression of moesin or radixin significantly reduced HCV protein expression. In contrast, transient knockdown of moesin or radixin augmented HCV infection. Making use of the Con1 HCV replicon system, we tested the effect of EMR proteins on HCV replication. We found that transient knockdown of moesin increased HCV RNA expression while overexpression of EMR showed no significant effect on HCV replication.Our findings demonstrate the important role of EMR proteins during HCV infection at the postentry level and highlight possible novel targets for HCV treatment.
How we can modify the steroid insensitivity in patients with chronic obstructive pulmonary disease? The new pharmacological approach to old problem
Authors: Alizaman Sadigov, Jabrail Mammadov, Gulzar Alieva
Journal: European Respiratory Journal (2011)

How we can modify the steroid insensitivity in patients with chronic obstructive pulmonary disease? The new pharmacological approach to old problem.  The aims of our study was the follow-up of efficacy of low-dose theophylline in patients with chronic obstructive pulmonary disease (COPD) 3 stage. We have examed 43 patients with severe COPD (GOLD, 3 stage) and all patients were divided two groups: 1) 23 patients have recieved teophylline 200mg/day and Seretide-Discus 1000/100/mcg/day + Tiotropium-bromide 18mcg/day; 2) 20 patients have recieved Seretide-Discus 1000/100 mcg/day + Tiotropium-bromide 18mcg/day without theophylline. All of patients with severe COPD were observed during 6 months. In all patients were investigated lung function, cell and sytokine (IL-8, IL-6, TNF-a) contents of induced sputum before and after treatment regime. Our investigation shown that low doses of phosphoinositide-3-kinase (PI3K) inhibitors (theophyllines) might be a useful addendum to steroid therapy in patients with severe COPD. Our study reported that twice daily dose (200mg) of teophylline significantly improved FEV1 (58,7±8,9% vs 51,6±7,5% in patients control, p
Does NICE COPD audit tools affect management of COPD
Authors: Samir Naik, Cheryl Khoong, Afreen Sultana
Journal: European Respiratory Journal (2013)

Objective: To audit COPD management using NICE COPD 2010 audit tool.  Method:  Data from 54 patients (62% males, mean ±SD age, 69± 12 years) attending the hospital was audited against NICE COPD audit Performa(2010). It was analysed further with respect to age, sex, ethnicity, assessment and management of COPD.  Findings:  Majority of our patients are Caucasians (74%) with slight male preponderance (62%) and older than 50years (92%)  Over all management was as per NICE recommendations except for overtreatment for Stage 2 COPD (6/15 = 40%).  Investigations were done appropriately.  Post bronchodilator spirometry to accurately stage COPD(14%) and prognostic factors like BMI, MRC dyspnoea score, BODE index was very poorly documented.  Smoking history(15%) was poorly documented but advice on smoking cessation was well done 12/15(80%).  Conclusions:  Documentation of prognostic factors like BMI, MRC dyspnoea score, BODE index and post bronchodilator spirometry did not affect the ideal management of patients. They received treatment as per NICE recommendations.  It would be useful to have NICE Quality standards for COPD components in the audit tool and use GOLD 2011 assessment criteria which is more patient focussed.