tbuckley/cabot-search huggingface dataset:
Abstract 3945: Association of inflammation-related microRNA gene expression in inflammatory bowel disease and IBD-associated colon cancer
Authors: Aaron J. Schetter, Judith A. Welsh, Elise D. Bowman, Curtis C. Harris
Journal: Cancer Research (2011)

Abstract Introduction: There is an undeniable link between chronic inflammation and cancer. Inflammatory bowel disease (i.e. ulcerative colitis [UC] and Crohn's disease [CD]) are conditions that lead to chronic inflammation of the colon and increased risk of colon cancer. Indentifying factors that contribute to inflammatory bowel disease (IBD) and IBD-associated cancers may allow for the development of therapeutic and preventive strategies for these diseases. Altered expression of microRNAs may contribute to these diseases. Methods: We examined the expression of 29 specific microRNAs by Taqman-based quantitative RTPCR using the Fluidigm 96.96 dynamic array system. The 29 microRNAs were selected based on a combination of our own preliminary microarray data on inflammatory bowel disease and published literature on microRNAs involved in inflammation or inflammatory bowel disease. RNA was extracted from colon tissues of 34 patients with CD, 33 patients with UC, 64 sporadic colon cancer patients, 14 patients with IBD-associated colon cancer and 18 patients with adenomas. We identified microRNAs associated with gross inflammation in UC and CD patients. We also compared microRNA expression profiles of sporadic tumors with IBD-associated tumors. Results: The expression of 18 microRNAs were significantly altered in gross inflammation of CD and 19 microRNAs were altered in gross inflammation of UC. In general, the expression patterns were similar comparing UC and Crohn's tissues, but 3 microRNAs were significantly different between the two diseases. Fifteen microRNAs were altered in sporadic colon cancer. The microRNA expression patterns of IBD-associated tumors were quite different from the expression patterns of sporadic colon tumors. Summary: We find evidence supporting that the chronic inflammation of both ulcerative colitis and Crohn's disease leads to a systematic change in microRNA expression patterns. Altered expression of microRNA may be in part responsible for the phenotypic affects of gross inflammation. The expression of miR-21, miR-135b and miR-192 were altered in similar ways in colon tumors as they were in chronic inflammation, suggesting that alteration of these specific microRNAs may in part be responsible for the elevated risk of cancer in these populations. We also find that sporadic tumors have different expression profiles that IBD-associated tumor, suggesting that the different etiology of these tumors results in different microRNA transcriptomic expression patterns. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2011-3945
Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors
Authors: L. Schirosi, N. Nannini, D. Nicoli, A. Cavazza, R. Valli, S. Buti, L. Garagnani, G. Sartori, F. Calabrese, A. Marchetti, F. Buttitta, L. Felicioni, M. Migaldi, F. Rea, F. Di Chiara, M.C. Mengoli, G. Rossi
Journal: Annals of Oncology (2012)
Amphetamine Withdrawal: Affective State, Sleep Patterns, and MHPG Excretion
Authors: ROBERT WATSON, ERNEST HARTMANN, JOSEPH J. SCHILDKRAUT
Journal: American Journal of Psychiatry (1972)

The authors found that the clinical depressions which occurred following withdrawal from amphetamines after prolonged abuse were temporally associated with a decrease in the excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), a metabolite of norepinephrine, and altered EEG sleep patterns including an increased amount of D sleep (REM sleep). As the depressions subsided, MHPG excretion increased and measures of D sleep decreased.
Selective penetration and pharmacological activity of lactosaminated albumin conjugates of adenine arabinoside 5-monophosphate (ara-AMP) in mouse liver.
Authors: L Fiume, A Mattioli, C Busi, C Accorsi
Journal: Gut (1984)

With the aim of improving the chemotherapeutic index of adenine arabinoside 5-monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes where it is digested in lysosomes. In mice, the L-[3H]SA-ara-AMP conjugates, intravenously injected, selectively penetrated the liver, only small quantities were taken up by cells of spleen, bone marrow, intestine, and brain. After administration of the conjugate to mice with Ectromelia virus hepatitis, ara-AMP was selectively concentrated in liver in a pharmacologically active form. If L-SA-ara-AMP conjugates behave in man as in mouse, their administration to patients with chronic hepatitis B should result in a selective concentration of ara-AMP in liver with a more efficient inhibition of virus replication accompanied by lower toxicity for other tissues.
Cardiac-Specific Inducible and Conditional Gene Targeting in Mice
Authors: Thomas Doetschman, Mohamad Azhar
Journal: Circulation Research (2012)

Mouse genetic engineering has revolutionized our understanding of the molecular and genetic basis of heart development and disease. This technology involves conditional tissue-specific and temporal transgenic and gene targeting approaches, as well as introduction of polymorphisms into the mouse genome. These approaches are increasingly used to elucidate the genetic pathways underlying tissue homeostasis, physiology, and pathophysiology of adult heart. They have also led to the development of clinically relevant models of human cardiac diseases. Here, we review the technologies and their limitations in general and the cardiovascular research community in particular.
Discrepancy between mRNA and protein expression of tumour suppressor maspin in synovial tissue may contribute to synovial hyperplasia in rheumatoid arthritis
Authors: J Schedel, O Distler, M Woenckhaus, B Simmen, B A Michel, U Müller-Ladner
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the expression of maspin in RA synovial tissue and compare it with the expression in osteoarthritis (OA) and normal synovial tissue (NS).Using specific primers for maspin, a 237 bp fragment was amplified from cDNA obtained from cultured RA, OA, and normal synovial fibroblasts (SF) by RT-PCR. Additionally, mRNA expression levels were determined quantitatively by real time PCR. mRNA expression of maspin was investigated on snap frozen and paraffin embedded synovial tissue sections by in situ hybridisation. Immunohistochemistry was used to identify the cell type expressing maspin. SDS-PAGE and western blotting were performed to evaluate the protein expression in cultured SF. To confirm protein synthesis in situ, immunohistochemistry with specific anti-maspin antibodies was performed in synovial tissue sections of patients with RA.RT-PCR showed expression of maspin in all cDNA samples from cultured SF. Maspin mRNA was found to be decreased in RA SF twofold and 70-fold compared with OA SF and NS SF, respectively. Maspin mRNA was expressed in RA, OA, and normal synovial tissue. Importantly, maspin transcripts were also found at sites of invasion into cartilage and bone. At the protein level, maspin could be detected in RA and, less prominently, OA SF. In RA synovial tissue, maspin protein was detected in only a few synovial lining cells.Maspin is expressed intensively in RA SF at the mRNA level, but only slightly at the protein level, possibly owing to down regulation of maspin; this may contribute to the hyperplasia of synovial tissue in RA.
Abstract IA10: Overcoming castration-resistant prostate cancer
Authors: Charles L. Sawyers
Journal: Cancer Research (2012)

Abstract Resistance to antiandrogen therapy is associated with increased expression of androgen receptor (AR) mRNA, AR gene amplification or AR mutation. Increased AR levels are necessary and sufficient to promote hormone-refractory growth in models and, paradoxically, alter the cellular response to classic AR antagonists such that they function as weak agonists. Therefore, second generation antiandrogens must overcome these resistance mechanisms. We searched for novel AR antagonists that might retain function in the context of increased AR expression through a cell-based screen. Using the high affinity AR agonist RU59063 as a starting point, we synthesized and screened over 200 compounds to construct a structure/activity profile that defines features of the scaffold essential for receptor binding and for maximal antagonism. We focused our further efforts on a novel compound MDV3100, which retains potent antiandrogen activity in cells expressing increased levels of AR, blocks AR function in mice and impairs the growth of LNCaP and LAPC-4 xenografts engineered to express high levels of AR, whereas bicalutamide had minimal activity. MDV3100 inhibits AR with 10-fold greater affinity than bicalutamide and functions through a novel mechanism of action that impairs nuclear translocation and DNA binding. MDV3100 produced sustained PSA responses (greater than 50% reduction) in about ∼55 percent of men with castrate-resistant prostate cancer in a 140 patient phase I-II clinical trial. In a phase III registration study of 1119 men with castration resistance, chemotherapy refractory prostate cancer, MDV3100 prolonged survival compared to best supportive care (18.4 months versus 13.6 months; hazard ratio 0.631). The heterogeneity of clinical response to anti-androgen therapy suggests additional molecular determinants of drug resistance. By conducting an integrated genomic analysis of 214 prostate cancers, we have defined a common set of molecular lesions and pathways that may define distinct subsets of prostate cancer as well as responder/non-responder populations to antiandrogen therapy. In preclinical models we found that tumors with PTEN loss are relatively insensitive to androgen ablation therapy due to reciprocal negative feedback between the AR and PI3K signaling pathways. PTEN-mediated resistance can be overcome with combined AR + PI3K pathway inhibition. Studies of these and other molecular abnormalities reveal unique features of prostate cancer progression with implications for downstream drug development. Citation Format: Charles L. Sawyers. Overcoming castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA10.
Novel Small-Molecule Inhibitors of Bcl-XL to Treat Lung Cancer
Authors: Dongkyoo Park, Andrew T. Magis, Rui Li, Taofeek K. Owonikoko, Gabriel L. Sica, Shi-Yong Sun, Suresh S. Ramalingam, Fadlo R. Khuri, Walter J. Curran, Xingming Deng
Journal: Cancer Research (2013)

Abstract Bcl-XL is a major antiapoptotic protein in the Bcl-2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl-2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. Here, we screened small molecules that selectively target the BH3 domain (aa 90–98) binding pocket of Bcl-XL using the UCSF DOCK 6.1 program suite and the NCI chemical library database. We identified two new Bcl-XL inhibitors (BXI-61 and BXI-72) that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells. Fluorescence polarization assay reveals that BXI-61 and BXI-72 preferentially bind to Bcl-XL protein but not Bcl2, Bcl-w, Bfl-1/A1, or Mcl-1 in vitro with high binding affinities. Treatment of cells with BXI-72 results in disruption of Bcl-XL/Bak or Bcl-XL/Bax interaction, oligomerization of Bak, and cytochrome c release from mitochondria. Importantly, BXI-61 and BXI-72 exhibit more potent efficacy against human lung cancer than ABT-737 but less degree in platelet reduction in vivo. BXI-72 overcomes acquired radioresistance of lung cancer. On the basis of our findings, the development of BXI(s) as a new class of anticancer agents is warranted and represents a novel strategy for improving lung cancer outcome. Cancer Res; 73(17); 5485–96. ©2013 AACR.
Effect of body position on gas exchange after thoracotomy.
Authors: D Seaton, N L Lapp, W K Morgan
Journal: Thorax (1979)

To determine the effect of change in body position on gas exchange after thoracotomy, 12 patients with potentially resectable lung tumours were studied before and 24 hours after operation. Measurements of arterial blood gas tension (PaO2, PaCO2), alveolar-arterial oxygen difference (A--adO2), venous admixture effect (Qs/Qt percent), and physiological dead space to tidal volume ratio (Vd/Vt), were made in the supine, and left and right lateral decubitus positions. Preoperatively, altering position did not affect gas exchange significantly. After thoracotomy in the lateral position with the unoperated side dependent, PaO2 was significantly higher, and A--adO2 and Qs/Qt percent significantly lower than in the supine position. Postoperatively, the lateral position with the side of thoracotomy dependent was usually associated with the worst gas exchange. Only three patients achieved their best postoperative gas exchange in this position. In two this may have resulted from dependent small airway closure during tidal breathing, due to airways obstruction and old age, and in the third from postoperative atelectasis in this unoperated lung. No significant changes in mean PaCO2, Vd/Vt, or minute ventilation (VE) occurred with different positioning.
Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury
Authors: Nikolaus Wenger, Eduardo Martin Moraud, Stanisa Raspopovic, Marco Bonizzato, Jack DiGiovanna, Pavel Musienko, Manfred Morari, Silvestro Micera, Grégoire Courtine
Journal: Science Translational Medicine (2014)

Closed-loop neuromodulation of spinal sensorimotor circuits allows high-fidelity control over leg movements in paralyzed rats.
Beyond Low-Density Lipoprotein Cholesterol
Authors: Benoit J. Arsenault, Jamal S. Rana, Erik S.G. Stroes, Jean-Pierre Després, Prediman K. Shah, John J.P. Kastelein, Nicholas J. Wareham, S. Matthijs Boekholdt, Kay-Tee Khaw
Journal: Journal of the American College of Cardiology (2009)
Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study
Authors: L. Licitra, R. Mesia, F. Rivera, É. Remenár, R. Hitt, J. Erfán, S. Rottey, A. Kawecki, D. Zabolotnyy, M. Benasso, S. Störkel, S. Senger, C. Stroh, J.B. Vermorken
Journal: Annals of Oncology (2010)
Bilateral radial head fractures in a martial arts athlete
Authors: N V Deshmukh, M S Shah
Journal: British Journal of Sports Medicine (2003)

Isolated radial head fractures, which are rare, comprise about 2% of all fractures around the elbow. A case is reported of bilateral radial head fracture in an international female athlete. Early recognition and aggressive rehabilitation is essential if an abrupt end to a promising sporting career is to be prevented.
Stent Coating With Titanium-Nitride-Oxide for Reduction of Neointimal Hyperplasia
Authors: Stephan Windecker, Isabella Mayer, Gabriella De Pasquale, Willibald Maier, Olaf Dirsch, Philip De Groot, Ya-Ping Wu, Georg Noll, Boris Leskosek, Bernhard Meier, Otto M. Hess
Journal: Circulation (2001)

Background — Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. Methods and Results — Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide–coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65±3%) compared with TiNOX 2 (72±5%; P &lt;0.05) and stainless steel (71±4%; P &lt;0.05). Platelet adhesion 48 hours after incubation with human plasma, however, was not different between TiNOX 1 (17±3%) and 2 (15±3%) but was significantly higher with stainless steel (23±2%; P &lt;0.05). Fibrinogen binding was significantly reduced with TiNOX 2 (54±3%) compared with TiNOX 1 (82±4%, P &lt;0.05) or stainless steel (100%, P &lt;0.05). Histomorphometry revealed a significantly larger neointimal area in stainless steel (2.61±1.12 mm 2 ) than in TiNOX 1–coated (1.47±0.84 mm 2 , P &lt;0.02) or TiNOX 2–coated (1.39±0.93 mm 2 , P &lt;0.02) stents. The reductions were 44% and 47%, respectively. Conclusions — TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.
Multiple pulmonary nodules: and if it was not a cancer
Authors: R. Borie, M.-P. Debray, G. Jondeau, B. Crestani
Journal: Thorax (2010)

Multiple pulmonary nodules: and if it was not a cancerA 72-year-old woman was admitted in the Cardiology Department for respiratory insufficiency.ECG revealed atrial fibrillation, and echocardiography revealed heart failure with an estimated left ventricular ejection fraction of 25%.Chest roentgenogram revealed multiple nodules, and chest CT scan revealed multiple dense nodules surrounded by ground-glass attenuation (halo sign) with unilateral pleural effusion (figure 1).A bronchoalveolar lavage was performed to rule out any infection.Anticoagulation was begun before a successful external cardioversion, followed by oral amiodarone treatment.Diuretics were increased without any other medication.One week later, a control chest CT scan revealed the disappearance of all nodules, as well as of the pleural effusion (figure 2).
Risk factors for lower airway bacterial colonization in chronic bronchitis
Authors: E. Monso, A. Rosell, G. Bonet, J. Manterola, P.j. Cardona, J. Ruiz, J. Morera
Journal: European Respiratory Journal (1999)

The aim of this study was to determine the prevalence and risk factors for lower airway bacterial colonization (LABC) in stable chronic bronchitis (CB). Forty-one outpatients with CB were enrolled in the study (age 63.8+/-9.1 yrs (mean+/-SD); forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 62.8+/-11.2; current/former smokers 24/17). All patients had normal chest radiographs and an indication for performing fibreoptic bronchoscopy (pulmonary nodule, remote haemoptysis). The protected specimen brush (PSB) was used for bacterial sampling, and concentrations > or = 1,000 colony-forming units (cfu) x mL(-1) were considered positive for LABC. The repeatability of the procedure in CB was assessed in a random subsample of 18 subjects. A 72.2% quantitative agreement was found in the repeatability assessment of the PSB technique. Positive PSB cultures, obtained in 9 out of 41 (22%) patients, mainly yielded Haemophilus influenzae. The logistic regression model, used to determine which variables were related to colonization, showed that LABC was associated with current smoking (odds ratio (OR) 9.83, confidence interval (CI) 1.16-83.20) and low FVC (OR 0.73, CI 0.65-0.81). Age and FEV1 were not related to LABC. It was concluded that the prevalence of LABC in stable CB is high (22%), and current smoking is an important risk factor.
Perphenazine-Amitriptyline in Neurotic Depressed Outpatients: A Controlled Collaborative Study
Authors: ROBERT V. DESILVERIO, KARL RICKELS, CHARLES C. WEISE, EDWARD L. CLARK, JAMES HUTCHINSON
Journal: American Journal of Psychiatry (1970)

The combination of perphenazine-amitriptyline was compared to each of its constituents in a double-blind study conducted with 138 depressed and anxious-depressed neurotic outpatients. Irrespective of drug, general practice patients improved the most, clinic patients somewhat less, and private psychiatric patients the least. Drug differences were limited to a few significant and borderline-significant effects present only at two weeks; they indicated that perphenazine produced the greatest improvement at this period.
The Position of Gnetales among Seed Plants: Overcoming Pitfalls of Chloroplast Phylogenomics
Authors: B. Zhong, T. Yonezawa, Y. Zhong, M. Hasegawa
Journal: Molecular Biology and Evolution (2010)

The phylogenetic position of Gnetales is one of the most contentious issues in the seed plant systematics. To elucidate the Gnetales position, an improved amino acid substitution matrix was estimated based on 64 chloroplast (cp) genomes and was applied to cp genome data including all three lineages of Gnetales in maximum likelihood analyses of proteins. Although the initial analysis strongly supported the sister relation of Gnetales with Cryptomeria (Cupressophyta or non-Pinaceae conifers) (the "Gnecup" hypothesis), the support seems to be caused by a long-branch attraction (LBA) artifact. Indeed, by removing fastest evolving proteins that are most likely associated with the LBA, the support drastically declined. Furthermore, another analysis of partial genome data with dense taxon sampling of conifers showed that, in psbC, rpl2, and rps7 proteins, there are many parallel amino acid substitutions between the lineages leading to Gnetales and to Cryptomeria, and by further excluding these three genes, the sister relation of Gnetales with Pinaceae (the "Gnepine" hypothesis) became supported. Overall, our analyses indicate that the LBA and parallel substitutions cause a seriously biased inference of phylogenetic position of Gnetales with the cp genome data.
Dietary Fiber, Vegetables, and Colon Cancer: Critical Review and Meta-analyses of the Epidemiologic Evidence
Authors: B. Trock, E. Lanza, P. Greenwald
Journal: JNCI Journal of the National Cancer Institute (1990)

Whether colon cancer risk can be modified by a diet rich in vegetables, grains, and fruit, and, if so, whether the protective factor is dietary fiber or other biologically active components correlated with a high-fiber diet are questions of active research interest. Because studies on diet are susceptible to bias from a number of sources, in this review we evaluated the adequacy of study methodology as well as study results to clarify how much protection, if any, is conferred by a high-fiber diet. The review consisted of an aggregate assessment of the strength of evidence from 37 observational epidemiologic studies as well as meta-analyses of data from 16 of the 23 case-control studies. Both types of analyses revealed that the majority of studies gave support for a protective effect associated with fiber-rich diets; an estimated combined odds ratio (OR) of 0.57 (95% confidence interval = 0.50, 0.64) was obtained when the highest and lowest quantiles of intake were compared. Risk estimates based on vegetable consumption (OR = 0.48) were only slightly more convincing than those based on an estimate of fiber intake (OR = 0.58), but the data do not permit discrimination between effects due to fiber and nonfiber effects due to vegetables.