tbuckley/cabot-search huggingface dataset:
Tumor cell invasion of von Hippel Lindau renal cell carcinoma cells is mediated by membrane type-1 matrix metalloproteinase.
Authors: Brenda L Petrella, Constance E Brinckerhoff
Journal: Molecular Cancer (2006)

Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC arising from mutations in the von Hippel Lindau (VHL) tumor suppressor. Successful RCC tumor suppression by VHL requires the negative regulation of hypoxia inducible factor alpha (HIF alpha) protein and its downstream targets. Thus, identification of HIF target genes responsible for RCC tumor progression will aid in the development of therapies for this disease. We previously identified membrane type-1 matrix metalloproteinase (MT1-MMP) as a transcriptional target of HIF-2alpha in RCC cells null for VHL and showed that MT1-MMP is overexpressed in these cells. MT1-MMP is a key regulator of tumor progression through its functions as a matrix-degrading enzyme, as well as its ability to cleave factors, such as adhesion molecules and other MMPs. The aim of this study was to investigate the contribution of MT1-MMP to the invasive potential of RCC cells using in vitro type I collagen degradation and invasion assays. We evaluated RCC cells wild-type (WT8) and null (pRc-9) for VHL for invasive characteristics and showed that the pRc-9 cells demonstrated a greater propensity for both invasion and degradation of a type I collagen matrix. Furthermore, overexpression of either HIF-2alpha or MT1-MMP in the poorly invasive cell line, WT8, promoted collagen degradation and invasion of these cells. Finally, using RNAi, we show that inhibition of MT1-MMP suppresses tumor cell invasion of RCC cells. Our results suggest that MT1-MMP is a major mediator of tumor cell invasiveness and type I collagen degradation by VHL RCC cells that express either MT1-MMP or HIF-2alpha. As such, MT1-MMP may represent a novel target for anti-invasion therapy for this disease.
Functional profiling of the gut microbiome in disease-associated inflammation
Authors: Daniela Börnigen, Xochitl C Morgan, Eric A Franzosa, Boyu Ren, Ramnik J Xavier, Wendy S Garrett, Curtis Huttenhower
Journal: Genome Medicine (2013)

The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.
Migraine Intervention With STARFlex Technology (MIST) Trial
Authors: Andrew Dowson, Michael J. Mullen, Richard Peatfield, Keith Muir, Arif Anis Khan, Christopher Wells, Susan L. Lipscombe, Trevor Rees, Joseph V. De Giovanni, W. Lindsay Morrison, David Hildick-Smith, Giles Elrington, W. Stewart Hillis, Iqbal S. Malik, Anthony Rickards
Journal: Circulation (2008)

Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in approximately 80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial.Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed > or = 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P=0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (P=0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient.This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.
Induction of DNA Damage-Inducible Gene GADD45β Contributes to Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Cells
Authors: Da-Liang Ou, Ying-Chun Shen, Sung-Liang Yu, Kuen-Feng Chen, Pei-Yen Yeh, Hsiang-Hsuan Fan, Wen-Chi Feng, Ching-Tzu Wang, Liang-In Lin, Chiun Hsu, Ann-Lii Cheng
Journal: Cancer Research (2010)

Markers that could accurately predict responses to the general kinase inhibitor sorafenib are needed to better leverage its clinical applications. In this study, we examined a hypothesized role in the drug response for the growth arrest DNA damage-inducible gene 45β (GADD45β), which is commonly underexpressed in hepatocellular carcinoma (HCC) where sorafenib may offer an important new therapeutic option. The anticancer activity of sorafenib-induced GADD45β expression was tested in a panel of HCC cell lines and xenograft models. We found that GADD45β mRNA and protein expression were induced relatively more prominently in HCC cells that were biologically sensitive to sorafenib treatment. GADD45β induction was not found after treatment with either the mitogen-activated protein kinase-extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 or the Raf inhibitor ZM336372, suggesting that GADD45β induction by sorafenib was independent of Raf/MEK/ERK signaling activity. However, c-Jun NH2-terminal kinase (JNK) kinase activation occurred preferentially in sorafenib-sensitive cells. Small interfering RNA-mediated knockdown of GADD45βor JNK kinase limited the proapoptotic effects of sorafenib in sorafenib-sensitive cells. We defined the -339/-267 region in the GADD45β promoter containing activator protein-1 and SP1-binding sites as a crucial region for GADD45β induction by sorafenib. Together, our findings suggest that GADD45β induction contributes to sorafenib-induced apoptosis in HCC cells, prompting further studies to validate its potential value in predicting sorafenib efficacy.
Motor Cars for Medical Men: Novelties and Tendencies Revealed at the Olympia Show
Authors: H. M. Buist
Journal: BMJ (1926)

TnE yearly international motor car show, which the Society of Motor Manufacturers and Traders opens to-day (Friday October 22nd), under the patronage of .the King, at Olympia, Kensington, will be available daily, Sunday next excepted, until 10 p.m. on Saturday, October 0Oth.The general motoring coilditior,s in prospect for the ensuing year, as far as mechanical and trading developments are revealed at this exhibition, were reviewed in these columns last week.It may be added now that 45.6 per cent.only of the makes of cars on the homie narket are of native origin, 25.4 per ceent.being French, 12.7 per cent.American, 7.5 per cent.Italian, and the rest Canadian, Belgian, German, Austrian, Irish, Spanish, or Swiss.Four- cylinder einginies are the predominant type, representing 54.6 per cent.; but six-cylinder types have increased greatly in number, constituting 36.6 per oent.There is only one twelve-cylinder engined car-the steel sleeve valvo 50/150 h.p.Daimler mentioned last week.But the number of eight-cylinder engined car types has been increased from sixteen to twenty, all the new eight-cylinder e ngines being single line constructions, the most noteworthy of which is the 35-h.p.Sunbeam.Of the score of types, three only have the cylinders V set in blocks of four.No fewer than twenty-seven new six-cylinder engined models' are introduced, the majority by British constructors, :ranging in size between 2 and 3 -itre cylinder content.This confirms the tendency disclosed at the Paris show a week previously, where every native manufacturer except three presented a six-cylinder engined car type.More- over, of that trio, two are known to have " small sixes " on the stocks. Twelve new
The Effects of Nucleotide Substitution Model Assumptions on Estimates of Nonparametric Bootstrap Support
Authors: Thomas R. Buckley, Clifford W. Cunningham
Journal: Molecular Biology and Evolution (2002)

The use of parameter-rich substitution models in molecular phylogenetics has been criticized on the basis that these models can cause a reduction both in accuracy and in the ability to discriminate among competing topologies. We have explored the relationship between nucleotide substitution model complexity and nonparametric bootstrap support under maximum likelihood (ML) for six data sets for which the true relationships are known with a high degree of certainty. We also performed equally weighted maximum parsimony analyses in order to assess the effects of ignoring branch length information during tree selection. We observed that maximum parsimony gave the lowest mean estimate of bootstrap support for the correct set of nodes relative to the ML models for every data set except one. For several data sets, we established that the exact distribution used to model among-site rate variation was critical for a successful phylogenetic analysis. Site-specific rate models were shown to perform very poorly relative to gamma and invariables sites models for several of the data sets most likely because of the gross underestimation of branch lengths. The invariable sites model also performed poorly for several data sets where this model had a poor fit to the data, suggesting that addition of the gamma distribution can be critical. Estimates of bootstrap support for the correct nodes often increased under gamma and invariable sites models relative to equal rates models. Our observations are contrary to the prediction that such models cause reduced confidence in phylogenetic hypotheses. Our results raise several issues regarding the process of model selection, and we briefly discuss model selection uncertainty and the role of sensitivity analyses in molecular phylogenetics.
Erratum to: The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material
Authors: Niall D. Ferguson, Eddy Fan, Luigi Camporota, Massimo Antonelli, Antonio Anzueto, Richard Beale, Laurent Brochard, Roy Brower, Andre´s Esteban, Luciano Gattinoni, Andrew Rhodes, Arthur S. Slutsky, Jean-Louis Vincent, Gordon D. Rubenfeld, B. Taylor Thompson, V. Marco Ranieri
Journal: Intensive Care Medicine (2012)
Basal Ganglia Circuits for Reward Value–Guided Behavior
Authors: Okihide Hikosaka, Hyoung F. Kim, Masaharu Yasuda, Shinya Yamamoto
Journal: Annual Review of Neuroscience (2014)

The basal ganglia are equipped with inhibitory and disinhibitory mechanisms that enable a subject to choose valuable objects and actions. Notably, a value can be determined flexibly by recent experience or stably by prolonged experience. Recent studies have revealed that the head and tail of the caudate nucleus selectively and differentially process flexible and stable values of visual objects. These signals are sent to the superior colliculus through different parts of the substantia nigra so that the animal looks preferentially at high-valued objects, but in different manners. Thus, relying on short-term value memories, the caudate head circuit allows the subject's gaze to move expectantly to recently valued objects. Relying on long-term value memories, the caudate tail circuit allows the subject's gaze to move automatically to previously valued objects. The basal ganglia also contain an equivalent parallel mechanism for action values. Such flexible–stable parallel mechanisms for object and action values create a highly adaptable system for decision making.
Association of thromboxane A1 synthase (TBXAS1) gene polymorphism with acute urticaria induced by nonsteroidal anti-inflammatory drugs
Authors: Carmen Vidal, Liliana Porras-Hurtado, Raquel Cruz, Joaquín Quiralte, Victoria Cardona, Carlos Colás, Luisa F. Castillo, Carmen Marcos, Teresa Soto, Raquel Lopez-Abad, Dolores Hernández, Maria Teresa Audicana, Margarita Armisén, Virginia Rodríguez, Celsa Perez-Carral, Esther Moreno, Rosario Cabañes, Mercè Corominas, Antonio Parra, Teófilo Lobera, Dolores Quiñones, Pedro Ojeda, Ildefonso Luna, María Torres, Angel Carracedo
Journal: Journal of Allergy and Clinical Immunology (2013)
Secretory leukoprotease inhibitor: a native antimicrobial protein presenting a new therapeutic option?
Authors: J F Tomee, G H Koëter, P S Hiemstra, H F Kauffman
Journal: Thorax (1998)

Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine protease inhibitor found on various mucosal surfaces and has been ascribed an important role in maintaining the protease-anti-protease balance of the airways. Recent scientific evidence has suggested that SLPI may also have a broad spectrum antibiotic activity that includes antiretroviral, bactericidal, and antifungal activity. Given the unpropitious development of drug resistance to infectious micro-organisms in the human population, the need for therapeutic alternatives in the treatment of infectious diseases has become clear. SLPI may prove valuable in the prophylaxis and future treatment of infectious diseases, yet the clinical efficacy of SLPI remains largely to be elucidated.
Retraction: The triterpenoid CDDO-Imidazolide induces apoptosis and enhances fludarabine-induced apoptosis of CLL B-cells
Authors: Irene M. Pedersen, Juan M. Zapata, Temesgen Samuel, Fiona L. Scott, Guy S. Salvesen, Tadashi Honda, Gordon W. Gribble, Nanjoo Suh, Michael B. Sporn, Thomas J. Kipps, John C. Reed
Journal: Blood (2004)
Treatment outcome of multi drug resistant tuberculosis patients in modified DOTS-PLUS: A new strategy
Authors: Rajendra Prasad, Abhijeet Singh, Ram Awadh Singh Kushwaha, Rajiv Garg, Sanjeev Kumar Verma, S. Saheer, Girdhar Hosmane, Rahul Srivastava, Amita Jain
Journal: European Respiratory Journal (2011)

Background: Multi Drug Resistant Tuberculosis is a worldwide problem and growing hazard to human health.

Aims and Objective: To study the treatment outcome with second line drugs in patients of MDR-TB in modified DOTS-PLUS strategy.

Methods: A prospective cohort study analysing 98 consecutive patients with MDR-TB attending the Dept of Pulmonary Medicine, CSMMU, between June 2009 to Feb 2010 with follow-up till Feb 2011. All the patients were given medications free of cost as per DOTS PLUS Protocol of India.Treatment included monthly followup,adherence check up,radiological and bacteriological assessment (sputum smear-monthly till conversion then quarterly;culture for MTB-0,4,6,12,18,24 months),health education and monitoring of adverse effects.Patients' outcome considered as “cure” when atleast 2of the last 3 cultures were negative and as “failure” when the same were positive.

Results: All the patients had resistance to at least Isoniazid and Rifampicin with mean no. of 3.02 drugs and were seronegative for HIV. Default rate at the end of 6 months and 12 months were observed in 2.1% and 4.1% patients respectively. 5 patients expired in initial 6 months and 2 in next 6 months. Sputum smear and culture conversion at the end of 6 months and 12 months were 80/90 (88.9%) and 75/90 (83.3%) and 81/87 (93.1) and 78/87 (89.7%) respectively. Mean smear and culture conversion time were 3.6±2.1 months and 4.1±2.6 months respectively. Significant side effects were experienced in 14.3% patients.

Conclusions: Culture conversion rates at the end of 6 months and 12 months were 83.3% and 89.7% respectively. Modified DOTS-PLUS strategy can be model for treatment of MDR-TB in private sector.
Analyses of pointing actions of top male competitors in karate at world level
Authors: Seied Mohammad Marandi, Vahid Zolaktaf, Mohammad Reza Batavani
Journal: British Journal of Sports Medicine (2010)

Karate takes a significant place in sport today. Work goal is determination of quantity indicators related to pointing action at sports fights at top-level male karate competitors. Pointing actions were analysed through basic pointing ways (attack, interception and counterattack) and pointing techniques that exist in sports fight and are defined by judging rules. Research is based on analysis of seven final matches at all weighting categories in male competition at the World Championships in Finland 2006. Collecting of data was performed by analysis of electronic material of completely recorded fights, and by Quintic software. For record of data, used from special forms that was assigned by 2 statistical experts and 15 coaches of Iran national karate team. Methods of descriptive statistical analyse and analyses of quantity differences were used for data processing. Result Quantity indicators show that men have pointed dominantly from attack (61.6%) while pointing from counterattack (19.6%) and interception (18.6%) have lower frequency, significantly (p≤0.05). Pointing techniques that have dominant frequency are combination techniques (36.7%), gjaku tsuki dzodan (18.1%) and gjaku tsuki cudan (7.7%). Besides that, gjaku tsuki dzodan (28.5%) was the most effective technique to take point. Head (66%), as most common goal area to achieve point (p≤0.05), doing the technique under pressure of opponent (34.2%), as most common pressure, central zone of Tatami (52.7%), as most motion area of actions, middle distance (38.4%), as most common distance from opponent, Uri asi forward (47.0%), as most common way to shortening of distance, middle open guard (36.7%) and middle close guard (29.2%), as most common offensive and defensive guards (respectively). Analyse, show that the following factors, which are very important for success and can leading to training systems.
Oral Magnesium Therapy Improves Endothelial Function in Patients With Coronary Artery Disease
Authors: Michael Shechter, Michael Sharir, Maura J. Paul Labrador, James Forrester, Burton Silver, C. Noel Bairey Merz
Journal: Circulation (2000)

Background —Magnesium blocks many of the physiological actions of calcium. Nevertheless, the impact of magnesium supplementation on endothelial function and exercise tolerance in stable coronary artery disease (CAD) patients has not been assessed. Methods and Results —In a randomized, double-blind, placebo-controlled trial, 50 stable CAD patients (41 men and 9 women, mean±SD age 67±11 years, age range 42 to 82 years) were randomized to receive either magnesium (n=25) (30 mmol/d Magnosolv-Granulat; Asta Medica Company, Inc) or placebo (n=25) for 6 months. Before and after 6 months, endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and endothelium-independent NTG-mediated vasodilation were assessed with high-resolution (10-MHz) ultrasound. Exercise stress testing was performed with use of the Bruce protocol. Intracellular magnesium concentrations ([Mg 2+ ] i ) were assessed from sublingual cells through x-ray dispersion (EXA) (normal mean±SD values 37.9±4.0 mEq/L). The magnesium therapy significantly increased postintervention ([Mg 2+ ] i versus placebo (36.2±5.0 versus 32.7±2.7 mEq/L, P &lt;0.02). There was a significant correlation in the total population between baseline [Mg 2+ ] i and baseline FMD ( r =0.48, P &lt;0.01). The magnesium intervention resulted in a significant improvement in postintervention FMD (15.5±12.0%, P =0.02 compared with baseline), which was not evident with placebo (4.4±2.5%, P =0.78 compared with baseline). There was better exercise tolerance (9.3±2.0 versus 7.3±3.1 minutes, P =0.05) and less ischemic ST-segment changes (4 versus 10 patients, P =0.05) in the magnesium versus placebo groups, respectively. Conclusions —Oral magnesium therapy in CAD patients is associated with significant improvement in brachial artery endothelial function and exercise tolerance, suggesting a potential mechanism by which magnesium could beneficially alter outcomes in CAD patients.
USE OF SALINE IN SOLUTIONS FOR LOCAL ANESTHESIA
Authors: Arthur E. Hertzler
Journal: JAMA (1933)

<h3>To the Editor:</h3> —In a recent review of my book on local anesthesia (The Journal, October 28, p. 1418) I am criticized for not advocating the use of physiologic solution of sodium chloride in making up the anesthetic solution. Why should one use it in making up anesthetic solution? I have tried about all the various mixtures advised for the making up of anesthetic solutions in the clinic, in my leg, and in bunnies and bow-wows. There is no difference in the "feel" injected in one's own skin, and slides of animal tissue show no injury when plain tap water is used. Clinical experience convinces me that anesthesia is more prompt when a hypotonic medicine is used. Wise boys tell me that theoretically a hypotonic solution is more quickly absorbed than an isotonic or a hypertonic one. Be it remembered that after one dissolves a few tablets of procaine in
BIOCHEMICAL STUDY OF CELLULAR ANTIGEN-ANTIBODY REACTION IN TISSUE CULTURE
Authors: Hideo Hayashi, Akira Tokuda, Keiji Udaka
Journal: The Journal of Experimental Medicine (1960)

The correlation between morphological and biochemical changes produced by the antigen-antibody reaction was studied in cultures of tissue monocytes taken from sensitized animals. The cells were grown under conditions which allowed collection of samples from the culture fluid as well as microscopic observation. Introduction of the antigen into the culture medium causes rapid release of a protease characterized by its susceptibility to sulfhydryl block and its optimum pH in the neutral range. Protease activation occurs simultaneously with morphological changes in the cytoplasm of the cultured cells. Delayed changes affecting the mitochondria and Golgi bodies appear after the peak of the proteolytic reaction and may be secondary to it. The gradual inactivation of the protease observed in the course of the antigen-antibody reaction will be discussed in a separate paper.