tbuckley/cabot-search huggingface dataset:
Abstract 3732: Utilizing Bimolecular Fluorescent Complementation to Identify Inhibitors of RAL and KRAS
Authors: Marytheresa Ifediba, David Burnett, Nicholas Hovda, William Burnett, Matthew VanBrocklin
Journal: Cancer Research (2014)

Abstract We have identified RAL activity to be vital for NSCLC survival independent of KRAS or EGFR mutation status in a large panel of adenocarcinomas and have developed a novel high throughput screening assay based on Bimolecular Fluorescent Complementation (BiFC) to identify small molecules that impair RAL function. Coupling RALA and RALB to the C-terminus of the Venus protein (VC) and coexpressing either with direct binding effector RALBP1 fused to the N-terminus of the Venus protein (VN) result in a fluorescent signal when RAL-RALBP1 binding occurs in cells. This allows for the interrogation of small molecules that disrupt RAL-RALBP1 binding interactions (resulting in loss of fluorescence) in a real time, high throughput manner. Our preliminary screen with a natural compound library identified 14 small molecules that demonstrated high activity in disrupting both RALA- and RALB-RALBP1 binding and fluorescence. We are currently investigating these compounds' mode of action and have recently expanded our assay to screen for molecules that impair mutant KRAS activity (VC-KRAS / RAF1-VN). BiFC provides a rapid, more physiologic method to identify molecules that can disrupt protein-protein interactions of targets considered ‘undruggable’, including membrane bound small GTPases such as RAL and KRAS. Citation Format: Marytheresa Ifediba, David Burnett, Nicholas Hovda, William Burnett, Matthew VanBrocklin. Utilizing Bimolecular Fluorescent Complementation to Identify Inhibitors of RAL and KRAS. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3732. doi:10.1158/1538-7445.AM2014-3732
ACCF/AHA Clinical Competence Statement on Cardiac Imaging With Computed Tomography and Magnetic Resonance
Authors: Matthew J. Budoff, Mylan C. Cohen, Mario J. Garcia, John Mc B. Hodgson, W. Gregory Hundley, Joao A.C. Lima, Warren J. Manning, Gerald M. Pohost, Paolo M. Raggi, George P. Rodgers, John A. Rumberger, Allen J. Taylor, Mark A. Creager, John W. Hirshfeld, Beverly H. Lorell, Geno Merli, Cynthia M. Tracy, Howard H. Weitz
Journal: Journal of the American College of Cardiology (2005)
First experience in Ukraine of endobronchial ultrasound transbronchial biopsy lungs (EBUS TBBL) in the differential diagnosis of peripheral lung diseases
Authors: Oksana Shpak, Victor Bychkovskiy, Aleksey Novitskiy, Raisa Demidova, Maria Yatsyna
Journal: European Respiratory Journal (2013)

A peripheral lung disease is manifestations of various diseases (tuberculosis, tumors, etc.) and requires obligatory morphological verification.   Objective:  to study the effectiveness of EBUS TBBL in the differential diagnosis of peripheral lung structures.   Materials and Methods:  In the period of 2011-2012 on the basis of the endoscopy department, it was performed 253 bronchofibroscopies under intravenous sedation with EBUS TBBL using ultrasonic probes OLYMPUS UM – BS20 – 26R and OLYMPUS UM – S20 – 20R. Biopsy was performed after setting ultrasonic probe in the center of formation by draining bronchus, frequency performance up to 5 times with further sending material for morphological examination. In this research were 165 men (65.2%) and 88 women (34.8%). The average age of patients was 35.6 years.   Results:  The diagnosis was confirmed morphologically in 244 cases (96.5%), of which 187 patients (73.9%) received diagnosis at cytology examination. Post-biopsy complications were observed in 1 case (4.3%) as hemoptysis at first day. Morphologically, the following diagnosis were found: pulmonary tuberculosis in 123 cases, tumors in 100 cases, of which 65 cases was adenocarcinoma, 25 cases was bronchoalveolar cancer and 10 cases were metastasis of other tumors, pulmonary manifestations of systemic vasculitis in 27 cases, pulmonary alveolar proteinases in 3 cases.   Conclusions  :  EBUS TBBL is low traumatic and minimally invasive diagnostic method. It has a fairly high rate of informativeness and efficiency, and is 96.5%. Thus, the use of EBUS TBBL is a highly informativeness method in the diagnosis of peripheral lung structures.
Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia.
Authors: M R O'Donnell, G D Long, P M Parker, J Niland, A Nademanee, M Amylon, N Chao, R S Negrin, G M Schmidt, M L Slovak
Journal: Journal of Clinical Oncology (1995)

PURPOSE A non-radiation-containing regimen of busulfan and cyclophosphamide (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients who received allogeneic bone marrow transplantation (BMT) for myelodysplasia (MDS). PATIENTS AND METHODS Thirty-eight patients with MDS, including eight with therapy-related MDS, were prepared for BMT using BU/CY. RESULTS Fourteen patients remain in first remission 18 to 60 months posttransplant. Five patients relapsed after BMT, and four of these patients died. Eight additional patients died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen-related toxicity, primarily systemic mycoses. Overall survival rate at 2 years was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily as hepatic dysfunction in 72% of patients, with 16% developing overt venoocclusive disease (VOD). CONCLUSION Non-radiation-containing preparative regimens offer long-term survival in allogeneic BMT for MDS that is comparable to that of radiation-containing regimens, and are useful in patients with therapy-related MDS. Monitoring BU levels may reduce regimen-related mortality and improve survival.
The consensus molecular subtypes of colorectal cancer
Authors: Justin Guinney, Rodrigo Dienstmann, Xin Wang, Aurélien de Reyniès, Andreas Schlicker, Charlotte Soneson, Laetitia Marisa, Paul Roepman, Gift Nyamundanda, Paolo Angelino, Brian M Bot, Jeffrey S Morris, Iris M Simon, Sarah Gerster, Evelyn Fessler, Felipe De Sousa E Melo, Edoardo Missiaglia, Hena Ramay, David Barras, Krisztian Homicsko, Dipen Maru, Ganiraju C Manyam, Bradley Broom, Valerie Boige, Beatriz Perez-Villamil, Ted Laderas, Ramon Salazar, Joe W Gray, Douglas Hanahan, Josep Tabernero, Rene Bernards, Stephen H Friend, Pierre Laurent-Puig, Jan Paul Medema, Anguraj Sadanandam, Lodewyk Wessels, Mauro Delorenzi, Scott Kopetz, Louis Vermeulen, Sabine Tejpar
Journal: Nature Medicine (2015)
Incidence and risk factors for acute exacerbations of asthma during pregnancy: A prospective observational study of 500 pregnancies
Authors: Zarqa Ali, Camilla Boslev Christensen, Thorbjørn Lomholt Gregersen, Charlotte Suppli Ulrik
Journal: European Respiratory Journal (2013)

Background and Aim:  Acute exacerbations of asthma during pregnancy have unfavourable impact on pregnancy outcome. We investigated incidence and risk factors for acute exacerbations during pregnancy.  Methods : Prospective observational design. Primary outcome was acute exacerbations of asthma during pregnancy. Case history was obtained, including exacerbation history, and patients had their asthma control, spirometry and exhaled nitric oxide assessed during regular visits.  Results:  A total of 500 pregnant women with asthma (defined according to GINA-guidelines) aged 17 to 44 years were included. At first visit (week 12-16 of pregnancy), spirometry revealed mean FEV 1  90.6%pred (range 43-128) and FEV 1 /FVC 0.82 (range 51-98); and mean F E NO 21.5 ppb (range 3-207). A total of 185 (37%) patients had at least one acute exacerbation of asthma during pregnancy; the incidence of acute exacerbations was highest in the 1. trimester of pregnancy (21.4%) compared with 13.0% and 7.2%, respectively, in 2. and 3. trimester. Apart from a higher risk associated with high F E NO (p=0.007) and treatment with inhaled corticosteroids (p Conclusion:  The incidence of acute exacerbation of asthma during pregnancy is high, especially in 1. trimester of pregnancy and in non-primipara mothers.
Clinical manifestations and prediction rules in patients with pulmonary embolism and prior respiratory disease
Authors: Renata Baez-Saldana, Monica Velazquez-Uncal, Isela Cisneros-Chavez, Octavio Aburto-Valencia
Journal: European Respiratory Journal (2011)

Introduction: Presently, little is known about de effect of prior respiratory disease on clinical manifestations and status on the pretest probability in patients with pulmonary embolism.  Objective: To describe clinical manifestations and status on the clinical prediction rules in patients with pulmonary embolism (PE) and prior respiratory disease (PRD).  Methods: We retrospectively analysed 118 cases with diagnosis of PE, in a referral hospital of respiratory diseases in Mexico City from 2007 to 2009.  Clinical information was taken form medical records and Wells and Geneva prediction rules were used to categorize the patient9s clinical pretest probability of PE.  Results: 56/118 (47%) patients with PE had one or two PRD: obstructive sleep apnea/hypopnea syndrome 25 (21%), COPD 14 (12%), pneumonia 15 (13%) interstitial lung disease 6 (5%), asthma 4 (3%), and lung cancer 2 (1.7%) cases.  Patients with PRD had higher prevalence of cough, sputum, deterioration of existing dyspnea, and wheezing; a lower prevalence of sudden onset of dyspnea and chest pain compared with the group with no PRD (p  Pretest probability according to Wells and Geneva criteria are shown in table 1.  Conclusions: Clinical identification of PE in patients with PRD is still difficult because of high proportion of nonspecific nature of symptoms. The status on the clinical prediction rules in patients with PE and PRD limits their use in this setting.
Carbon Monoxide Poisoning
Authors: Ivan Blumenthal
Journal: Journal of the Royal Society of Medicine (2001)

The deadly effect of carbon monoxide was known as long ago as Greek and Roman times, when the gas was used for executions1. In 1857 Claude Bernard postulated that its noxious effect was caused by reversible displacement of oxygen from haemoglobin to form carboxyhaemoglobin2. In 1926 it became apparent that hypoxia was caused not only by deficient oxygen transport but also by poor tissue uptake. Warberg used yeast cultures to show that cellular uptake of oxygen was inhibited by exposure to a large amount of carbon monoxide3.

Carbon monoxide is known as the silent killer since it has no colour or smell. Each year in Britain about 50 people die and 200 are severely injured by carbon monoxide poisoning4. Some poisonings are caused by self-harm but most are accidental5. It is the commonest cause of accidental poisoning and, according to one estimate, as many as 25000 people in the UK have symptoms due to faulty gas appliances4. In the 1960s and 1970s the conversion from coal gas to carbon-monoxide-free natural gas caused a dramatic reduction in poisoning6. In this review I discuss modern approaches to management and prevention.
Role of microRNA 17/92 cluster and microRNA 21 in the pathogenesis of pulmonary hypertension - Novel therapeutic targets
Authors: S. Pullamsetti, C. Doebele, A. Fischer, R. Savai, B. Kojonazarov, B. Dahal, H. Ghofrani, N. Weissmann, F. Grimminger, A. Bonauer, W. Seeger, A. Zeiher, S. Dimmeler, R. Schermuly
Journal: European Respiratory Journal (2013)

MicroRNAs (miRs) control various cellular processes in tissue homeostasis and disease by regulating gene expression on the post-transcriptional level. Recently, it was demonstrated that expression of miR-21 and miR-17–92 cluster was significantly altered in pulmonary hypertension (PH).  To evaluate the therapeutic efficacy and anti-remodeling potential of miR inhibitors in the pathogenesis of PH, we used miR inhibitors (antagomirs), which were specifically designed to block miR-17(A-17), miR-21(A-21), and miR-92a(A-92a) in chronic hypoxia-induced PH (HOX-PH) in mice and A-17 in monocrotaline-induced PH (MCT-PH) in rats. Moreover, biological function of miR-17 was analyzed in pulmonary artery smooth muscle cells (PASMCs).  In HOX-PH mouse model, A-17 and A- 21 reduced right ventricular systolic pressure (RVSP). However, only A-17 reduced hypoxia-induced right ventricular hypertrophy and improved pulmonary artery acceleration time (PAAcT). In the MCT-PH rat model, A-17 treatment significantly decreased RVSP, increased PAAcT, normalized cardiac output, and decreased pulmonary vascular remodeling. Among the tested miR-17 targets, p21, BMPR2 and ID1 were upregulated in lungs undergoing A-17 treatment. Likewise, in human PASMCs, A-17 increased p21. Overexpression of miR-17 significantly reduced p21 expression and increased proliferation of PASMCs.  Our data demonstrate that A-17 improves heart and lung function in experimental PH by interfering with lung vascular and right ventricular remodeling. The beneficial effects may be related to upregulation of p21. Thus, inhibition of miR-17 may represent a novel therapeutic concept for treatment of PH.
Muscle regrowth in COPD patients induced by anabolic steroids is amplified by systemic glucocorticoids (GC): A potentiating interaction between GC and IGF-1?
Authors: Nicholas A.M. Pansters, Ramon C.J. Langen, Annemie M.W.J. Schols
Journal: European Respiratory Journal (2011)

Muscle wasting is associated with poor prognosis in COPD. Anabolic steroids can induce muscle regrowth and stimulate muscle insulin growth factor 1 (IGF-1) signaling, while high dose systemic glucocorticoids (GC) can induce muscle atrophy. The current study aimed to gain insight into the combined effect of GC and anabolic stimulation on muscle. Post-hoc analysis of a previously published clinical trial (Creutzberg, et al. Chest 2003; 124:1733–1742) investigating nandrolone decanoate (ND) efficacy on male COPD patients revealed that gain in fat-free mass (assessed by deuterium dilution), was highest in ND/GC 2.27±0.42 kg (mean±SEM; p 2-fold) and IGF-I stimulated (>2.5-fold) multiple parameters of muscle differentiation, like Creatine Kinase activity, muscle contractile protein content and myoblast fusion. However when combined, a synergistic stimulation (>3-fold) of myogenic differentiation parameters was observed, which is in line with our clinical data. Unraveling the potentiating interaction between GC and IGF-I may provide new leads to enhance efficacy of intervention strategies to prevent/or restore muscle wasting in COPD.
Pleural amyloidosis: thoracoscopic aspects
Authors: F Bontemps, I Tillie-Leblond, MC Coppin, P Frehart, B Wallaert, P Ramon, AB Tonnel
Journal: European Respiratory Journal (1995)

We describe the case of a 60 year old man with primary amyloidosis, who suffered from peripheral neuropathy and cardiomyopathy and who presented with recurrent right pleural effusion. For this reason, he was admitted to hospital for thoracoscopic examination with pleurodesis. Macroscopic examination of the parietal pleura revealed a diffuse inflammation and light brown deposits that where covered with nodules. Biopsy specimens confirmed the amyloid deposition. This macroscopic appearance is described for the first time, and suggests that a local pleural synthesis of amyloid substance may occur during the course of systemic amyloidosis.
Propofol versus midazolam for conscious sedation in medical thoracoscopy: A randomized non-inferiority trial
Authors: Peter Grendelmeier, Eric Pflimlin, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2013)

Background:  Propofol has been established as a reliable method for conscious sedation in patients undergoing flexible bronchoscopy. However, there are only limited data about sedation-related complications in medical thoracoscopy using propofol. Moreover, there are no data directly comparing propofol sedation with another regimen for conscious sedation in medical thoracoscopy.   Methods:  90 consecutive patients undergoing medical thoracoscopy were randomly allocated to receive either intravenous propofol or midazolam. The primary endpoint was mean lowest oxygen saturation during the procedure.   Results:  The mean lowest oxygen saturation during the procedure was significantly lower in the propofol group (93 ± 6 % in propofol group vs. 96 ± 3 % in midazolam group; p = 0.007). Hypoxemia defined as an oxygen saturation ≤ 90 % was seen more frequently in the propofol group (12 (27 %) vs. 2 (4 %), p = 0.007). Similarly, hypotension defined as a systolic pressure ≤ 90 %, was more common in the propofol group (37 (82 %) vs. 18 (40 %), p =    Conclusions:  Propofol is associated with a higher incidence of adverse events than midazolam in medical thoracoscopy. In contrast to flexible bronchoscopy, propofol should not be considered the first choice for conscious sedation in medical thoracoscopy.
Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression
Authors: Henrik Zetterberg, Tobias Skillbäck, Niklas Mattsson, John Q. Trojanowski, Erik Portelius, Leslie M. Shaw, Michael W. Weiner, Kaj Blennow
Journal: JAMA Neurology (2015)

The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons.To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD.A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014.Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group.Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (β = 598.7, P < .001).Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.
Chemotherapy of extragonadal germ cell tumors.
Authors: C J Logothetis, M L Samuels, D E Selig, F H Dexeus, D E Johnson, D A Swanson, A C von Eschenbach
Journal: Journal of Clinical Oncology (1985)

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.
Different Radioiodine Dose for Remnant Thyroid Ablation in Patients With Differentiated Thyroid Cancer
Authors: Xinghua Song, Zhaowei Meng, Qiang Jia, Linlin Zhang, Ke Xu, Jian Tan, Guizhi Zhang, Wei Zheng, Xue Li, Jianping Zhang
Journal: Clinical Nuclear Medicine (2015)

Remnant thyroid ablation is crucial in the management of patients with differentiated thyroid cancer. However, the optimal dose of radioactive I for ablation is still controversial. This study aimed to compare the success rate of different activities of I for postoperative remnant ablation in randomized controlled trials (RCTs) and to determine the optimal dose.Sources were retrieved from the Cochrane Library, Medline, Embase, Scopus, and Google Scholar until March 2014. All RCTs that assessed the efficacy of different doses of I for ablation were selected. After data extraction, statistics were performed by Review Manager 5.2 software.Seventeen RCTs were considered eligible, involving 3737 patients. The overall methodological quality of the studies was good. The rate of successful remnant ablation of low versus moderate I activities (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.80-1.00; P = 0.06) and moderate versus high I activities (RR, 0.94; 95% CI, 0.89-1.00; P = 0.05) showed no significant differences. However, high I activities had 11% higher successful ablation rate than low activities with an RR of 0.89 (95% CI, 0.81-0.97; P = 0.008), which was significant.We summarized all available randomized evidence to demonstrate that high dose of I was significantly better than low dose to achieve successful remnant thyroid ablation.
Prevalence of chlamydial infection in a series of 108 primary cutaneous lymphomas
Authors: A.J.M. Ferreri, M. Ponzoni, S. Govi, E. Pasini, S. Mappa, A. Vino, F. Facchetti, P. Vezzoli, C. Doglioni, E. Berti, R. Dolcetti
Journal: British Journal of Dermatology (2011)
Hepatotoxicity in Wistar Rats Following Chronic Methotrexate Administration: A Model of Human Reaction2
Authors: R. Philip Custer, Marian Freeman-Narrod, Stuart A. Narrod
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Hepatotoxicity in Wistar Rats Following Chronic Methotrexate Administration: A Model of Human Reaction Get access R. Philip Custer, R. Philip Custer Search for other works by this author on: Oxford Academic PubMed Google Scholar Marian Freeman-Narrod, Marian Freeman-Narrod 5 5Address reprint requests to Dr. Marian Freeman-Narrod. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart A. Narrod Stuart A. Narrod Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 1011–1017, https://doi.org/10.1093/jnci/58.4.1011 Published: 01 April 1977 Article history Received: 15 June 1976 Accepted: 20 September 1976 Published: 01 April 1977