tbuckley/cabot-search huggingface dataset:
Quantitation of Promoter Methylation of Multiple Genes in Urine DNA and Bladder Cancer Detection
Authors: Mohammad Obaidul Hoque, Shahnaz Begum, Ozlem Topaloglu, Aditi Chatterjee, Eli Rosenbaum, Wim Van Criekinge, William H Westra, Mark Schoenberg, Marianna Zahurak, Steven N Goodman, David Sidransky
Journal: JNCI Journal of the National Cancer Institute (2006)

The noninvasive identification of bladder tumors may improve disease control and prevent disease progression. Aberrant promoter methylation (i.e., hypermethylation) is a major mechanism for silencing tumor suppressor genes and other cancer-associated genes in many human cancers, including bladder cancer.A quantitative fluorogenic real-time polymerase chain reaction (PCR) assay was used to examine primary tumor DNA and urine sediment DNA from 15 patients with bladder cancer and 25 control subjects for promoter hypermethylation of nine genes (APC, ARF, CDH1, GSTP1, MGMT, CDKN2A, RARbeta2, RASSF1A, and TIMP3) to identify potential biomarkers for bladder cancer. We then used these markers to examine urine sediment DNA samples from an additional 160 patients with bladder cancers of various stages and grades and from an additional 69 age-matched control subjects. Data were analyzed on the basis of a prediction model and were internally validated using a jacknife procedure. All statistical tests were two-sided.For all 15 patients with paired DNA samples, the promoter methylation pattern in urine matched that in the primary tumors. Four genes displayed 100% specificity. Of the 175 bladder cancer patients, 121 (69%, 95% confidence interval [CI] = 62% to 76%) displayed promoter methylation in at least one of these genes (CDKN2A, ARF, MGMT, and GSTP1), whereas all control subjects were negative for such methylation (100% specificity, 95% CI = 96% to 100%). A logistic prediction model using the methylation levels of all remaining five genes was developed and internally validated for subjects who were negative on the four-gene panel. This combined, two-stage predictor produced an internally validated ROC curve with an overall sensitivity of 82% (95% CI = 75 % to 87%) and specificity of 96% (95% CI = 90% to 99%).Testing a small panel of genes with the quantitative methylation-specific PCR assay in urine sediment DNA is a powerful noninvasive approach for the detection of bladder cancer. Larger independent confirmatory cohorts with longitudinal follow-up will be required in future studies to define the impact of this technology on early detection, prognosis, and disease monitoring before clinical application.
A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families
Authors: Willem M. Lijfering, Nic J. G. M. Veeger, Saskia Middeldorp, Karly Hamulyák, Martin H. Prins, Harry R. Büller, Jan van der Meer
Journal: Blood (2009)
Overexpression of Aurora-A in primary cells interferes with S-phase entry by diminishing Cyclin D1 dependent activities
Authors: Florian Jantscher, Christine Pirker, Christoph-Erik Mayer, Walter Berger, Hedwig Sutterluety
Journal: Molecular Cancer (2011)

Abstract Background Aurora-A is a bona-fide oncogene whose expression is associated with genomic instability and malignant transformation. In several types of cancer, gene amplification and/or increased protein levels of Aurora-A are a common feature. Results In this report, we describe that inhibition of cell proliferation is the main effect observed after transient overexpression of Aurora-A in primary human cells. In addition to the known cell cycle block at the G2/M transition, Aurora-A overexpressing cells fail to overcome the restriction point at the G1/S transition due to diminished RB phosphorylation caused by reduced Cyclin D1 expression. Consequently, overexpression of Cyclin D1 protein is able to override the Aurora-A mediated G1 block. The Aurora-A mediated cell cycle arrest in G2 is not influenced by Cyclin D1 and as a consequence cells accumulate in G2. Upon deactivation of p53 part of the cells evade this premitotic arrest to become aneuploid. Conclusion Our studies describe that an increase of Aurora-A expression levels on its own has a tumor suppressing function, but in combination with the appropriate altered intracellular setting it might exert its oncogenic potential. The presented data indicate that deactivation of the tumor suppressor RB is one of the requirements for overriding a cell cycle checkpoint triggered by increased Aurora-A levels.
Compliance with a comprehensive warm-up programme to prevent injuries in youth football
Authors: Torbjørn Soligard, Agnethe Nilstad, Kathrin Steffen, Grethe Myklebust, Ingar Holme, Jiri Dvorak, Roald Bahr, Thor Einar Andersen
Journal: British Journal of Sports Medicine (2010)

Participants' compliance, attitudes and beliefs have the potential to influence the efficacy of an intervention greatly.To characterise team and player compliance with a comprehensive injury prevention warm-up programme for football (The 11+), and to assess attitudes towards injury prevention among coaches and their association with compliance and injury risk.A prospective cohort study and retrospective survey based on a cluster-randomised controlled trial with teams as the unit of randomisation.Compliance, exposure and injuries were registered prospectively in 65 of 125 football teams (1055 of 1892 female Norwegian players aged 13-17 years and 65 of 125 coaches) throughout one football season (March-October 2007). Standardised telephone interviews were conducted to assess coaches' attitudes towards injury prevention.Teams completed the injury prevention programme in 77% (mean 1.3 sessions per week) of all training and match sessions, and players in 79% (mean 0.8 sessions per week) of the sessions they attended. Compared with players with intermediate compliance, players with high compliance with the programme had a 35% lower risk of all injuries (RR 0.65, 95% CI 0.46 to 0.91, p=0.011). Coaches who had previously utilised injury prevention training coached teams with a 46% lower risk of injury (OR 0.54, 95% CI 0.33 to 0.87, p=0.011).Compliance with the injury prevention programme was high, and players with high compliance had significantly lower injury risk than players with intermediate compliance. Positive attitudes towards injury prevention correlated with high compliance and lower injury risk.
Letting Go of the Rope — Aggressive Treatment, Hospice Care, and Open Access
Authors: Alexi A. Wright, Ingrid T. Katz
Journal: New England Journal of Medicine (2007)

Interview with Timothy Quill on hospice care in the United States. (06:55)Download More Americans are choosing hospice for end-of-life care, but ironically, hospice patients increasingly are forced to give up effective palliative treatments along with aggressive medical intervention. For Joanne Doolin, a 64-year-old mother of three who spent her last 2 years of life fighting colon cancer that eventually made it impossible to eat, enrollment in hospice care involved a difficult trade-off: with only a few weeks left to live and her daughter's wedding approaching, Doolin was forced to choose between entering hospice care and continuing to receive total parenteral nutritional support.Unfortunately, treatment options are often limited by the economic constraints . . .
Feedback Inhibition of Catecholamine Release by Two Different α <sub>2</sub> -Adrenoceptor Subtypes Prevents Progression of Heart Failure
Authors: Marc Brede, Frank Wiesmann, Roland Jahns, Kerstin Hadamek, Carsten Arnolt, Stefan Neubauer, Martin J. Lohse, Lutz Hein
Journal: Circulation (2002)

Elevated plasma norepinephrine levels are associated with increased mortality in patients and in animal models with chronic heart failure. To test which alpha2-adrenoceptor subtypes operate as presynaptic inhibitory receptors to control norepinephrine release in heart failure, we investigated the response of gene-targeted mice lacking alpha2-adrenoceptor subtypes (alpha2-KO) to chronic left ventricular pressure overload. In addition, we determined the functional consequences of genetic variants of alpha2-adrenoceptors in human patients with chronic heart failure.Cardiac pressure overload was induced by transverse aortic constriction. Three months after aortic banding, survival was dramatically reduced in alpha2A-KO (52%) and alpha2C-KO (47%) mice compared with wild-type and alpha2B-deficient (86%) animals. Excess mortality in alpha2A- and alpha2C-KO strains was attributable to heart failure with enhanced left ventricular hypertrophy and fibrosis and elevated circulating catecholamines. The clinical importance of this finding is emphasized by the fact that heart failure patients with a dysfunctional variant of the alpha2C-adrenoceptor had a worse clinical status and decreased cardiac function as determined by invasive catheterization and by echocardiography.Our results indicate an essential function of alpha2A- and alpha2C-adrenoceptors in the prevention of heart failure progression in mice and human patients. Identification of heart failure patients with genetic alpha2-adrenoceptor variants as well as new alpha2-receptor subtype-selective drugs may represent novel therapeutic strategies in chronic heart failure and other diseases with enhanced sympathetic activation.
Relationship between Rh0(D) Zygosity and Red Cell Rh0(D) Antigen Content in Family Members*
Authors: S. P. Masouredis, Mary Edith Dupuy, Margaret Elliot
Journal: Journal of Clinical Investigation (1967)

The red cells of 63 members of 11 families were tested with 125I-labeled anti-Rh0(D). Families with a history of hemolytic disease of the newborn due to fetomaternal Rh incompatibility were selected for study. In such families it was possible to determine the antibody binding to the Rh0(D) heterozygous red cells of the children and to compare within each family this value with the antibody bound to the father's Rh0(D)-positive red cells and the mother's Rh0(D)-negative red cells. The fathers in all the families studied could be assigned to two classes on the basis of the quantity of antibody bound to their red cells. One group bound about the same quantity of antibody to their cells as did their children, indicating that they were heterozygous for the Rh0(D) antigen. The other bound about twice as much antibody to their cells as did their children, indicating that they were homozygous for the antigen. The Rh genotype of the father in all 11 families could be ascertained by using the children in each family as a reference point. The members of two families showed a poor correspondence between antibody binding and zygosity. In one family an Rh heterozygous child (R1r) took up 85% of the antibody bound to the father's homozygous cells (R1R1), and in the other family an Rh heterozygous child (R1r) took up 20% more antibody than did the cells of her father, which were of the same Rh phenotype (Rh1) and zygosity.
Time-Varying Myocardial Stress and Systolic Pressure-Stress Relationship
Authors: Julio A. Chirinos, Patrick Segers, Amit Kumar Gupta, Abigail Swillens, Ernst R. Rietzschel, Marc L. De Buyzere, James N. Kirkpatrick, Thierry C. Gillebert, Yan Wang, Martin G. Keane, Raymond Townsend, Victor A. Ferrari, Susan E. Wiegers, Martin St John Sutton
Journal: Circulation (2009)

Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress in hypertensive and normotensive adults.We studied 42 untreated hypertensive, 42 treated hypertensive, and 42 normotensive adults with normal LV ejection fraction. Time-resolved central pressure, flow, and LV geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography for computation of arterial load and time-varying circumferential and longitudinal myocardial stress. In all 3 groups, peak myocardial stress typically occurred in early systole (within the first 100 milliseconds of ejection), followed by a marked midsystolic shift in the pressure-stress relationship, which favored lower late systolic stress values (P<0.001) relative to pressure. The mean magnitude of this midsystolic shift was quantitatively important in all 3 groups (circumferential stress, 144 to 148 kdynes/cm(2)) and was independently predicted by a higher LV ejection fraction and ratio of LV end-diastolic cavity to wall volume. Time of peak myocardial stress independently correlated with time of the first systolic but not with time of the second systolic central pressure peak.Peak myocardial stress occurs in early systole, before important contributions of reflected waves to central pressure. In the presence of normal LV ejection fraction, a midsystolic shift in the pressure-stress relationship protects cardiomyocytes against excessive late systolic stress (despite pressure augmentation associated with wave reflections), a coupling mechanism that may be altered in various disease states.
Neuronal Computations in the Olfactory System of Zebrafish
Authors: Rainer W. Friedrich
Journal: Annual Review of Neuroscience (2013)

The main olfactory system encodes information about molecules in a combinatorial fashion by distributed spatiotemporal activity patterns. As activity propagates from sensory neurons to the olfactory bulb and to higher brain areas, odor information is processed by multiple transformations of these activity patterns. This review discusses neuronal computations associated with such transformations in the olfactory system of zebrafish, a small vertebrate that offers advantages for the quantitative analysis and manipulation of neuronal activity in the intact brain. The review focuses on pattern decorrelation in the olfactory bulb and on the readout of multiplexed sensory representations in the telencephalic area Dp, the homolog of the olfactory cortex. These computations are difficult to study in larger species and may provide insights into general information-processing strategies in the brain.
Cavernous Haemangioma with Kasabach-Merritt Syndrome: Treatment with Alpha-Interferon
Authors: J J Ettlinger, P J Fleming, H S Joffe, C T C Kennedy
Journal: Journal of the Royal Society of Medicine (1996)

A small number of patients with haemangioma need treatment for serious complications such as Kasabach-Merritt syndrome, cardiac failure and obstruction of the airway. We report on the management of an infant with Kasabach-Merritt syndrome.
Complementarity of stenting and abciximab for percutaneous coronary intervention
Authors: D.J. Koreiakos, A.M. Lincoff, M.L. Simoons, M.J. deBoer, J.E. Tcheng, A. Vahanian, K.M. Anderson, H.F. Weisman, R.A. Califf, E.J. Topol
Journal: Journal of the American College of Cardiology (1998)
A High Level of CCAAT-Enhancer Binding Protein-δ Expression Is a Major Determinant for Markedly Elevated Differential Gene Expression of the Platelet-Derived Growth Factor-α Receptor in Vascular Smooth Muscle Cells of Genetically Hypertensive Rats
Authors: Yutaka Kitami, Tomikazu Fukuoka, Kunio Hiwada, Tadashi Inagami
Journal: Circulation Research (1999)

Abstract —Platelet-derived growth factor-α receptor (PDGF-αR) expression is markedly elevated in cultured vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) when compared with normotensive rat strains, Sprague-Dawley, Wistar, and Wistar-Kyoto rats (WKY). This “almost-all-or-none” type of differential expression strongly suggests that PDGF-αR or its transcription-regulating mechanisms or factors are significantly related to genetic hypertension. To evaluate the role of PDGF-αR in vascular remodeling and hypertension, we have investigated the underlying molecular mechanism. We have recently shown that the regulatory domain responsible for this difference is localized to the PDGF-αR promoter region between –246 and –139, which contains an enhancer core sequence specific for CCAAT-enhancer binding proteins (C/EBPs). We defined the roles of this element for hypertensive strain-specific PDGF-αR gene transcription. DNA-protein binding studies by competition in electromobility shift and supershift assays revealed that 2 members, C/EBP-β and C/EBP-δ, are mainly responsible for DNA-protein complex formation; the former acts as a transcriptional repressor and the latter as an activator of the PDGF-αR gene, respectively. Western or Northern blot analyses supported evidence for high expression of C/EBP-δ seen only in SHR-derived VSMCs. Furthermore, forced expression of C/EBP-δ transactivated the transcriptional efficiency of the PDGF-αR gene even in WKY-derived VSMCs, whereas that of C/EBP-β had an opposite effect in SHR-derived VSMCs. These findings indicate that differential expression of members of the C/EBP family, mainly C/EBP-δ and possibly C/EBP-β, are responsible for the strain-specific gene transcription of PDGF-αR in VSMCs.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1936)

The coccobacilliform bodies of fowl coryza were successfully cultivated in the fetal membranes of fertile eggs. Microscopic examination indicated growth in approximately 50 per cent of 94 eggs inoculated on the 3rd to 4th day of incubation. Growth was generally inhibited, however, in eggs inoculated on the 10th day. One strain of the specific bodies was maintained through 11 successive passages in 4 day eggs. A more consistent growth of the coccobacilliform bodies was obtained in tissue cultures. One strain, originally isolated in November, 1935, has been carried through 100 successive subcultures at intervals of 1-3 days. The specific bodies fail to maintain their morphological identity for any length of time in this medium. It is noted that growth of the coccobacilliform bodies in fertile eggs and in tissue cultures is not dependent on the presence of living cells.
Oxygen saturation during daily activities in chronic obstructive pulmonary disease
Authors: N Soguel Schenkel, L Burdet, B de Muralt, JW Fitting
Journal: European Respiratory Journal (1996)

Patients with chronic obstructive pulmonary disease (COPD) frequently develop nocturnal oxygen desturation because of alveolar hypoventilation, worsening of ventilation-perfusion mismatch, and sometimes obstructive sleep apnoeas. In contrast, little is known about their oxygen status during the various activities of daily life. The aim of this study was to compare the oxygen saturation profile during day and night, and to assess the influence of different daily activities in COPD. During a rehabilitation programme, we studied 30 patients with moderate-to-severe COPD (median forced expiratory volume in one second (FEV1) 37% of predicted), without marked hypoxaemia (median arterial oxygen tension (Pa,O2) 9.1 kPa). Arterial oxygen saturation (Sa,O2) was assessed by pulse oximetry during night (8 h) and day (10.5 h). The mean and minimal Sa,O2 were calculated, and desaturations were defined as Sa,O2 falls &gt; 4%.h-1. Daily activities were identified by the patients as resting, eating, washing, nebulization therapy and walking. Mean Sa,O2 was lower during the night (88%) than during the day (89%). In contrast, minimal Sa,O2 was lower during the day (69%) than during the night (72%), and the number of desaturations was higher during the day (8.6 desaturations.h-1) than during the night (6.8 desaturations.h-1). Mean Sa,O2 was 88% during walking, which was lower than during resting (90%), nebulization (90%), and meals (89%). The number of desaturations was higher during walking (13.1 desaturations.h-1), washing (12.6 desaturations.h-1), and eating (9.2 desaturations.h-1) than during resting (5.3 desaturations.h-1). We conclude that daily activities, such as walking, washing and eating, are associated with transient oxygen desaturation in patients with moderate-to-severe chronic obstructive pulmonary disease, even without marked resting hypoxaemia.
A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150
Authors: A. Belch, C.T. Kouroukis, M. Crump, L. Sehn, R.D. Gascoyne, R. Klasa, J. Powers, J. Wright, E.A. Eisenhauer
Journal: Annals of Oncology (2006)
Predominant Bcl-XL Knockdown Disables Antiapoptotic Mechanisms: Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Based Triple Chemotherapy Overcomes Chemoresistance in Pancreatic Cancer Cells <i>In vitro</i>
Authors: Jirong Bai, Jianhua Sui, Aram Demirjian, Charles M. Vollmer, Wayne Marasco, Mark P. Callery
Journal: Cancer Research (2005)

Abstract Pancreatic cancer is lethal because of its invasiveness, rapid progression, and profound resistance to chemotherapy and radiation therapy. To identify the molecular mechanisms underlying this, we have examined the expression and potency of three major death receptors: tumor necrosis factor receptor (TNF-R), TNF-related apoptosis-inducing ligand receptor (TRAIL-R), and Fas in mediating cytotoxicity in four invasive pancreatic cancer cell lines. We have analyzed the expression of major antiapoptotic factors, cell cycle regulators and death receptor decoys (DcR) in comparison with normal pancreas tissues and five other human malignant tumor cell lines. We have found that different pancreatic cancer cell lines coexpress high-level TRAIL-R, Fas, and TNF-R1 but are strongly resistant to apoptosis triggered by the death receptors. DcR2 and DcR3 overexpression may partly contribute to the resistance of pancreatic cancer cells to TRAIL-R– and Fas-mediated cytotoxicity. Bcl-XL and Bcl-2 are predominantly overexpressed in pancreatic cancer cell lines, respectively. Bcl-XL is also predominantly overexpressed in prostate, colorectal, and intestinal cancer cells. The knockdown of the predominant Bcl-XL overexpression significantly reduces the viability of pancreatic cancer cells to TNFα- and TRAIL-mediated apoptosis by sublethal-dose single and combined antitumor drugs, including geldanamycin, PS-341, Trichostatin A, and doxorubicine. Geldanamyin and PS-341 synergistically block NFκB activation, suppress Akt/PKB pathway, and down-regulate Bcl-XL, Bcl-2, cIAP-1, and cyclin D1 expression. This combined regimen dramatically enhances TRAIL cytotoxic effects and breaks through chemoresistance. Bcl-XL plays a vital role in pancreatic cancer chemoresistance. Geldanamycin, PS-341, and TRAIL triple combination may be a novel therapeutic strategy for pancreatic cancer.
Community-acquired respiratory viruses after lung transplantation: common, sometimes silent, potentially lethal
Authors: Allan R Glanville
Journal: Thorax (2013)

Community-acquired respiratory viruses (CARV) represent an ever present risk to the lung transplant (LTX) recipient.1 Alone among solid organ transplants, the lung allograft is exposed to the ambient environment with every breath; hence, it is exposed to CARV, which may trigger rejection.2 Or at least we once thought despite some recent evidence to the contrary.3–5 The current article in the journal expands the previous work of the same group and provides a comprehensive analysis of 112 patients examined on 903 occasions over a 3-year period with a further 2-year follow-up to determine the presence and effects of CARV.6–8 The results are compelling in the main. CARV account for about 30% of all acute respiratory presentations after LTX and are a dominant cause of new respiratory symptoms with a risk of hospitalisation of 17–50% depending on type. Surprisingly, 10% of asymptomatic LTX recipients had a positive test for CARV at screening visits (predominantly rhinovirus), but whether their asymptomatic status represents the effects of maintenance immune suppressive therapy on the inflammatory response cannot be ascertained from the study.

The major strength of this prospective study is the exhaustive assessment of both symptomatic …