tbuckley/cabot-search huggingface dataset:
Abstract 380: Serine-Arginine protein kinase 1 (SRPK1) - A potential target of angiogenesis in prostate cancer.
Authors: Athina Mavrou, Sebastian Oltean, Dave Bates
Journal: Cancer Research (2013)

Abstract Angiogenesis is required for all tumors to grow and metastasize and is mainly induced by the vascular endothelial growth factor (VEGF). Alternative spliced isoforms associated with cancer progression have been described in all areas of hallmarks of cancer, including angiogenesis. VEGF mRNA is alternatively spliced at the terminal exon, to produce two families of isoforms. The pro- angiogenic family, VEGFxxx, was shown to be up-regulated in all cancers studied so far, where as the anti- angiogenic family is preferentially expressed in normal non-angiogenic tissues, but down-regulated in most cancers. One of the factors involved in the regulation of VEGF alternative splicing is SRPK1. This is a protein kinase that phosphorylates the splicing factor SRSF1 and favours the production of the pro-angiogenic VEGF isoform. We therefore tested the hypothesis that down - regulation of SRPK1 in prostate cancer cells would increase the production of the anti-angiogenic isoform, preventing angiogenesis and tumor growth. PC-3, DU145 and LnCap prostate cancer cells showed an increased expression of SRPK1 when compared to Primary Prostate epithelial cells. Stable SRPK1 knock-down (KD) in PC-3 and LnCap prostate cancer cells was obtained using a lentiviral system (Dharmacon). This resulted in a reduction in splice factor expression, mainly SRSF1, and induced a switch in the expression of VEGF towards the anti-angiogenic isoform, VEGF165b, when compared to control cells (transfected with non-targeting shRNA). PC-3 SRPK1 KD and control cell lines were injected subcutaneously in male nude mice. Knock down of SRPK1 resulted in an inhibition of tumour growth, as shown by the significant difference in tumor size between the SRPK1 KD (250.0 ± 82.28 n=9) and control cell line (994.7 ± 243.5 n=9)(Day 29 post-injection). In addition to the reduction in tumor volume, SRPK1 inhibition resulted in decrease in vascular density of the tumors, as shown by the significant reduction in blood vessel number in PC-3 SRPK1 KD (2.714 ± 0.3686 n=7) mice compared with control (4.292 ± 0.5426 n=8). These in vitro and in vivo data suggest that the regulation of VEGF splicing by SRPK1 alters prostate cancer tumour growth and angiogenesis. Citation Format: Athina Mavrou, Sebastian Oltean, Dave Bates. Serine-Arginine protein kinase 1 (SRPK1) - A potential target of angiogenesis in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2013-380
Tolerance to phosgene is associated with a neutrophilic influx into the rat lung.
Authors: A J Ghio, G E Hatch
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Exposures to 100% oxygen, ozone, nitrogen oxides, and phosgene increase both lung lavage protein concentrations and neutrophils. The inhibition of the neutrophil influx can diminish lavage protein concentrations after exposures to these oxidant gases. Similarly, this injury can be reduced by pre-exposure to either the same (tolerance) or a different (cross-tolerance) oxidant gas. We tested the hypothesis that diminished injury after the development of tolerance of phosgene (COCl2) is associated with a decreased incursion of neutrophils. Sixty-day-old rats (n=12/group) were exposed to varying concentrations of COCl2. Lung lavage (n = 6/group) 24 h after a first phosgene exposure demonstrated an increase in both protein concentrations and percentage neutrophils. The remaining animals (n = 6/group) were exposed to COCl2 2 ppm x 60 min 1 wk later. Lavage confirmed the development of tolerance with protein concentrations diminished after the second exposure in those rats that had inhaled higher doses of COCl2 during the first exposure. However, the neutrophilic influx was not diminished but rather was increased. The association of the neutrophil incursion with a protective effect was further established in studies employing colchicine and dextran. Colchicine decreased neutrophil influx occurring after the first exposure and subsequently diminished the development of tolerance after a second exposure. Intratracheal instillation of dextran produced a neutrophil incursion and subsequently decreased injury after a phosgene exposure. In investigations using both colchicine and dextran, neutrophil influx increased with the development of adaptation. Thus, lung injury after the development of tolerance to phosgene provides a unique animal model of a respiratory distress syndrome in which neutrophils are not associated with injury but rather with a protective effect.
Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction.
Authors: T Omland, R T Lie, A Aakvaag, T Aarsland, K Dickstein
Journal: Circulation (1994)

BACKGROUND Plasma endothelin concentrations are increased in the acute phase of myocardial infarction and in chronic heart failure. Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction. METHODS AND RESULTS We tested the hypothesis that plasma endothelin determination in the subacute phase of myocardial infarction is related to subsequent survival and assessed whether plasma endothelin measurements provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma endothelin determination was obtained from 142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented myocardial infarction and was related to 1-year mortality. Sixteen patients died during the follow-up period. In a univariate Cox proportional-hazards model, day 3 plasma endothelin concentrations were significantly related to mortality (P &lt; .0001). Patient age, previous treatment for systemic hypertension, presence of clinical heart failure, and plasma atrial natriuretic factor levels were all related to mortality in univariate analysis but provided no additional prognostic information to that obtained from endothelin determination in a multivariate model. CONCLUSIONS Plasma endothelin concentrations are strongly related to outcome after myocardial infarction and provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis.
Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction
Authors: Wei Cao, Laura Bover, Minkwon Cho, Xiaoxia Wen, Shino Hanabuchi, Musheng Bao, David B. Rosen, Yi-Hong Wang, Joanne L. Shaw, Qiumei Du, Chun Li, Naoko Arai, Zhengbin Yao, Lewis L. Lanier, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2009)

Plasmacytoid dendritic cells (pDCs) produce copious type I interferon (IFN) upon sensing nucleic acids through Toll-like receptor (TLR) 7 and TLR9. Uncontrolled pDC activation and IFN production are implicated in lymphopenia and autoimmune diseases; therefore, a mechanism controlling pDC IFN production is essential. Human pDCs specifically express an orphan receptor, immunoglobulin-like transcript 7 (ILT7). Here, we discovered an ILT7 ligand expressed by human cell lines and identified it as bone marrow stromal cell antigen 2 (BST2; CD317). BST2 directly binds to purified ILT7 protein, initiates signaling via the ILT7–FcεRIγ complex, and strongly inhibits production of IFN and proinflammatory cytokines by pDCs. Readily induced by IFN and other proinflammatory cytokines, BST2 may modulate the human pDC’s IFN responses through ILT7 in a negative feedback fashion.
Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection
Authors: Michael P. Manns, Marc Bourlière, Yves Benhamou, Stanislas Pol, Maurizio Bonacini, Christian Trepo, David Wright, Thomas Berg, José L. Calleja, Peter W. White, Jerry O. Stern, Gerhard Steinmann, Chan-Loi Yong, George Kukolj, Joe Scherer, Wulf O. Boecher
Journal: Journal of Hepatology (2010)
Utility of 3-D echocardiography in patient selection and guidance for Atrial Septal Defect (ASD) closure by the new das-angel wings occluder device
Authors: Giuseppina Magni, Ziyad M. Hijazi, Gerald Marx, Gladwin Das, Alain Delabays, Jamie Levine, David Fulton, Natesa Pandian
Journal: Journal of the American College of Cardiology (1996)
Nitric Oxide Provokes Tumor Necrosis Factor-α Expression in Adult Feline Myocardium Through a cGMP-Dependent Pathway
Authors: Dinesh Kalra, Georg Baumgarten, Ziad Dibbs, Yukihiro Seta, Natarajan Sivasubramanian, Douglas L. Mann
Journal: Circulation (2000)

The mechanism(s) responsible for the persistent coexpression of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the failing heart is unknown.To determine whether NO was sufficient to provoke TNF-alpha biosynthesis, we examined the effects of an NO donor, S-nitroso-N-acetyl penicillamine (SNAP), in buffer-perfused Langendorff hearts. SNAP (1 micromol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF-alpha mRNA and protein biosynthesis in adult cat hearts. The effects of SNAP were completely abrogated by a NO quenching agent, 2-(4-carboxyphenyl)-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (C-PTIO), and mimicked by sodium nitroprusside. Electrophoretic mobility shift assays demonstrated that SNAP treatment led to the rapid induction of nuclear factor kappa-beta (NF-kappaB) but not AP-1. The importance of the cGMP pathway in terms of mediating NO-induced TNF-alpha biosynthesis was shown by studies that demonstrated that 8-bromo-cGMP mimicked the effects of SNAP and that the effects of SNAP could be completely abrogated using a cGMP antagonist, 1H-(1,2, 4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or protein kinase G antagonist (Rp-8-Br-cGMPS). SNAP and 8-Br-cGMP were both sufficient to lead to the site-specific phosphorylation (serine 32) and degradation of IkappaBalpha in isolated cardiac myocytes. Finally, protein kinase G was sufficient to directly phosphorylate IkappaBalpha on serine 32, a critical step in the activation of NF-kappaB.These studies show that NO provokes TNF-alpha biosynthesis through a cGMP-dependent pathway, which suggests that the coincident expression of TNF-alpha and NO may foster self-sustaining positive autocrine/paracrine feedback inflammatory circuits within the failing heart.
A NEW PERIMETER.
Authors: CHARLES H. WILLIAMS
Journal: JAMA (1898)

In testing the field of vision it is desirable to have the same illumination of the test object in all parts of the field, and to be able to diminish the intensity of this illumination by a known and measured amount when we wish to test the field for white or colors in cases of beginning atrophy or other conditions where there is a marked difference in the extent or shape of the field of vision when tested with a full and with a diminished amount of light. This seems to be best accomplished by making the tests in a dark room and using two incandescent electric lights of one candle power each for the test object and the fixation point. A Förster's perimeter with a broad semicircular arc of hard rubber is arranged so that one lamp is placed in the center of the arc and about an inch
Imaging Mitogen-Activated Protein Kinase Function in Xenograft Models of Prostate Cancer
Authors: Romyla Ilagan, Jill Pottratz, Kim Le, Liqun Zhang, Steven G. Wong, Raul Ayala, Meera Iyer, Lily Wu, Sanjiv S. Gambhir, Michael Carey
Journal: Cancer Research (2006)

Mitogen-activated protein kinases (MAPK) play important roles in malignancy. The ability to detect and quantitate MAPKs in live animal models of cancer will facilitate an understanding of disease progression. We have developed a gene expression-based imaging system that detects and quantifies MAPK activity in prostate cancer tumors implanted into severe combined immunodeficient mice. The imaging technology uses a modified version of two-step transcriptional amplification (TSTA). The tissue specificity of gene expression is imparted by an enhanced version of the prostate-specific antigen regulatory region that expresses GAL4-ELK1. GAL4-ELK1 confers MAPK specificity by activating a firefly luciferase (FLuc) reporter gene when the Ets-like transcription factor (ELK) 1 activation domain is phosphorylated by MAPK. FLuc activity in live animals was detected using the Xenogen In vivo Imaging System. We validated the TSTA-ELK1 system by analyzing its response to epidermal growth factor treatment in transfected tissue culture cells and in adenovirus (AdTSTA-ELK1)-injected prostate cancer xenograft tumors. We measured MAPK activity in two well-characterized xenograft models, CWR22 and LAPC9. Although no significant differences in MAPK levels were detected between androgen-dependent and androgen-independent xenografts, the CWR22 models display significantly higher levels of AdTSTA-ELK1 activity versus LAPC9. Western blots of tumor extracts showed that the elevated imaging signal in CWR22 xenografts correlated with elevated levels of phosphorylated extracellular signal-regulated kinase 1/2 but not p38 or c-Jun NH(2)-terminal kinase. We conclude that a gene expression-based optical imaging system can accurately detect and quantify MAPK activity in live animals.
Atlas of Flexible Bronchofiberscopy
Authors: Werner D. Chasin
Journal: JAMA (1975)

This handsomely produced atlas describes Dr. Ikeda's development of the flexible fiberoptic bronchoscope and its clinical application in the diagnosis of early lung lesions. The book can be regarded as a textbook of modern bronchoscopy. The text is profusely illustrated in both black and white and in color, and the reproductions represent the photographic perfection that we have come to expect of our Japanese colleagues. The English in this translation is idiomatic and contains only minor errors. In part 1, Dr. Ikeda discusses the development of the bronchoscope, the indications and techniques of performing flexible bronchofiberscopy, photographic recording methods, and a revised system of bronchoscopic anatomy that includes the more peripheral bronchi that are now reachable with the new flexible bronchoscopes. Part 2, a compilation of individual case presentations illustrating the diagnosis of early lesions, is replete with exemplary roentgenologic reproductions and superb color photographic illustrations of endoscopic findings, cytologic
Detection of microalbuminuria. Receiver operating characteristic curve analysis favors albumin-to-creatinine ratio over albumin concentration.
Authors: A J Bakker
Journal: Diabetes Care (1999)

OBJECTIVE: To compare albumin-to-creatinine ratio (ACR) and albumin concentration (ALB) for detection of microalbuminuria using precise data on CIs for sensitivity and specificity and to determine sex- and age-specific discriminator values for ACR. RESEARCH DESIGN AND METHODS: All consecutive patients investigated for the presence of microalbuminuria with timed overnight urine collection were included in the study. Results from 1.171 men and 1,223 women were eligible for evaluation. Albumin excretion rate (the reference procedure), ALB, and ACR were compared by receiver operating characteristic (ROC) curve analysis. Age- and sex-specific discriminator values were established. Sensitivity and specificity were determined, and their CIs were compared with those calculated from data presented in the literature. RESULTS: Sensitivity and specificity were 89% (range, 85-92) and 90% (88-92), respectively, for women, and 90% (87-93) and 89% (86-91), respectively, for men, at a discriminator value of 15 mg/l for the ALB. This discriminator value did not show any relationship to sex or age. For the ACR, which depends on sex, the sensitivity and specificity were 94% (92-96) and 92% (91-94), respectively, at 2.5 g/mol for women and 94% (92-97) and 93% (91-95), respectively, at 1.8 g/mol for men. The discriminator value for the ACR appears to depend on age in both men and women. CONCLUSIONS: ROC curve analysis clearly shows that the ACR performs better than the ALB in screening for microalbuminuria. However, in contrast to the ALB, the ACR needs sex- and age-specific discriminator values.
Risque de cancer colorectal à long-terme après résection d'un premier adénome: étude en population générale
Authors: V Cottet, AM Bouvier, V Jooste, J Faivre, C Bonithon-Kopp
Journal: Endoscopy (2010)

Introduction: La détection et la résection des adénomes par coloscopie est l'un des moyens de prévention du cancer colorectal. Le bénéfice de leur résection en pratique médicale de routine est encore mal évalué. L'objectif de cette étude était d'évaluer le risque de survenue à long terme d'un cancer colorectal dans une cohorte de patients ayant eu pour la première fois une résection d'adénome colorectal, comparativement à la population générale.
TCT-22 Combination of High Wall Shear Stress, Plaque Burden, and Plaque Phenotype has Incremental Value for Prediction of Increased Plaque Vulnerability in Patients with Coronary Artery Disease
Authors: Michel Corban, Parham Eshtehardi, Michael McDaniel, Jin Suo, Saurabh Dhawan, Charles Maynard, Lucas Timmins, Arshed Quyyumi, Don Giddens, Habib Samady
Journal: Journal of the American College of Cardiology (2012)
Abstract 776: Sensitization of glioblastoma cells to temozolomide induced antitumor effect by PLGA-aspirin microsphere through modulation of β-catenin transactivation
Authors: Zhendong Shi, Xiaomin Qian, Lei Han, Kailiang Zhang, Shanjun Zhu, Jialin Zhu, Fengming Lan, Junxia Zhang, Chunzhi Zhang, Peiyu Pu, Xubo Yuan, Chunsheng Kang
Journal: Cancer Research (2012)

Abstract Malignant gliomas are the most prevalent and deadliest brain neoplasms. Although temozolomide (TMZ) was currently used for treating glioblastoma patients, the recurrence was commonly existed due to the acquired therapeutic resistance. Thus the combination chemotherapy with TMZ is considered a promising therapeutic strategy in overcoming therapeutic resistance and improving treatment efficacy. In this study, we performed PLGA microspheres of aspirin and TMZ by spray drying technique and detected their cytotoxicity to glioblastoma cells. In vitro assay, PLGA-aspirin (PLGA-A) microsphere treatment revealed a slight inhibition of proliferation, invasion, as well as slightly induced apoptosis of A172 and U87 cells through inhibition of β-catenin transactivation in comparison with PLGA microsphere and Control group. In addition, the limited antitumor effect was also demonstrated in vivo. However, PLGA-aspirin-temozolomide (PLGA-A-T) microsphere treatment group displayed enhancing antitumor efficacy compared with PLGA-temozolomide (PLGA-T) microsphere group. IC50 values were dramatically decreased in cells treated with PLGA-A-T microsphere, to a greater extent than those treated with PLGA-A microsphere. Meanwhile, the PLGA-A-T microsphere significantly enhanced apoptosis in both A172 cells and U87 cells, and cell proliferation and invasiveness were obviously weakened. In response to the inhibition of β-catenin signaling, β-catenin/TCF4 transcriptional activity and STAT3 luciferase activity was strongly inhibited, as well as a greater decrease of mRNA and protein expression levels of β-catenin, TCF4, pAKT and pSTAT3.Similar results were also observed in vivo, intratumoral injection of PLGA-A-T microsphere significantly downregulated expression of β-catenin, TCF4, pAKT, pSTAT3 and PCNA, and also delayed tumor growth in nude mice harboring subcutaneous U87 xenografts. These results indicated that the synergistic cytotoxic effect of aspirin and temozolomide was achieved by aspirin- temozolomide -loaded PLGA nanoparticles through inhibition of β-catenin transactivation, offering the potential for improved treatment of glioblastomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 776. doi:1538-7445.AM2012-776
Quantitative evaluation of the regional left ventricular function in normal subjects by means of cineangiocardiography
Authors: A. BARSOTTI, R. MARIOTTI, A. BALBARINI, M. MARIANI
Journal: Cardiovascular Research (1980)

A method for analysing left ventricular cineangiograms is described, which not only provides information on the overall ventricular performance, but also evaluates the regional contraction of the left ventricle and the related haemodynamic patterns. This simplified Chapman's method (slice method) makes it possible to calculate the end-diastolic, end-systolic volumes, the stroke volume and the ejection fraction of the zones into which the left ventricle is divided by a longitudinal and by three transverse axes, according to Herman's technique. The hemiventriculograms of 21 normal subjects in the AP projection were evaluated using this method and a 10 of them were also studied in RAO projection. A uniform left ventricular contraction pattern was found for three hemiventricles outlined by the anterolateral, lateral, and postero-medial walls (ejection fraction 71.7 ± 5.1%, 71.6 ± 5.9%, 70.4 ± 5.1 %, respectively), the regional and zonal ejection fraction (EFR, EFZ) being similar in both projections. The ejection fraction of the hemiventricle outlined by the septal wall was, however, lower (65.6 ± 6.0%). The standard zonal function curves of the left ventricle in normal subjects was then calculated on the basis of the results obtained, in order to assess, by comparison, zonal function abnormalities in cardiac patients.
Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38α pathway
Authors: E Dassé, L Bridoux, T Baranek, E Lambert, S Salesse, M L Sowa, L Martiny, C Trentesaux, E Petitfrère
Journal: Leukemia (2007)
A villainous doctor
Authors: Theodore Dalrymple
Journal: BMJ (2011)

As Herbert Kinnell pointed out in the last Christmas edition of the BMJ , Agatha Christie’s novels have a lot of doctors, an inordinate number of them murderers ( BMJ 2010;341:c6438, doi:10.1136/bmj.c6438). In Cards on the Table (1936) Dr Roberts is not the only villain of the piece, but he is certainly one of the villains of the piece.

The story is convoluted, but to object that it is implausible is like objecting that the story of Little Red Riding Hood is implausible. Fairy stories are not to be confused with social realism, any more than revolutions are to be confused with dinner parties. Indeed, in Christie’s novels dinner parties …
Genetic Disorders of Renal Phosphate Transport
Authors: Dominique Prié, Gérard Friedlander
Journal: New England Journal of Medicine (2010)

This review recounts the molecular mechanisms that control serum phosphate levels and describes the clinical consequences of abnormalities of these mechanisms. Several proteins in the kidney participate in reabsorption of urinary phosphate; the review describes mutations in the genes that encode these proteins, and the syndromes they produce.