tbuckley/cabot-search huggingface dataset:
Abstract A21: Direct transcriptional functions of the APC tumor suppressor in regulating gene expression
Authors: William Hankey, Michael A. McIlhatton, Xun Lan, Anil G. Jegga, Victor X. Jin, Bruce J. Aronow, Joanna Groden
Journal: Cancer Research (2013)

Abstract Mutation of the APC tumor suppressor gene occurs in approximately 75% of colorectal cancers (CRC) and is considered the central event driving tumor initiation in the large intestine. The APC protein controls gene expression indirectly through the canonical WNT signaling pathway as a component of a cytoplasmic complex that promotes the proteolysis of the transcriptional co-regulator β-catenin. Recent studies have shown that APC is also a chromatin-associated protein that interacts with the promoter of the MYC proto-oncogene to downregulate its transcription. We have tested the hypothesis that APC similarly regulates other genes relevant to tumorigenesis, and that the 75% of CRCs that are deficient in APC may show abnormal activation or suppression of these genes, in comparison to the other 25% of CRCs. These differences could potentially underlie differences in tumor progression and/or responses to chemotherapy, and could enable the identification of new therapeutic targets. The APC genotype of two CRC cell lines was manipulated using siRNA to reduce APC expression in one cell line wild-type for APC and using an APC transgene to induce exogenous APC expression in a second cell line mutated for APC. NanoString and RNA-seq technologies have generated gene expression datasets from these cell lines and identify more than 700 genes that could be directly regulated at the transcriptional level by APC. RT-PCR and in silico analyses have validated a smaller subset of these genes. Functional pathway analysis has led to the hypothesis that APC loss facilitates evasion of apoptosis, with a subset of 17 pro- and anti-apoptotic candidate genes implicated in this effect. Critical experiments in progress will confirm the extent to which the aberrant expression of these genes in vivo is specific to colon tumors lacking APC, using Apc-deficient and Apc-wild-type mouse models of intestinal cancer, and will identify direct chromatin binding sites of APC by ChIP-seq. These approaches will validate our gene expression analyses and identify a set of direct gene targets that APC regulates. Citation Format: William Hankey, Michael A. McIlhatton, Xun Lan, Anil G. Jegga, Victor X. Jin, Bruce J. Aronow, Joanna Groden. Direct transcriptional functions of the APC tumor suppressor in regulating gene expression. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A21.
Improving mortality of coronary surgery: Study conclusions are paradoxical
Authors: Eric Lim
Journal: BMJ (2004)

EDITOR—The findings of the study by Bridgewater et al of improving mortality of coronary surgery over the first four years of independent practice in 15 surgeons are relevant and clinically important.1 But aren't the conclusions paradoxical?

The authors report that mortality in patients operated on by newly appointed consultant surgeons is similar to …
Effects of thyroid state and beta adrenergic stimulation on mechanical restitution of rat ventricular myocardium
Authors: R BOTTINELLI, C POGGESI, B POLLA, C REGGIANI
Journal: Cardiovascular Research (1988)

Journal Article Effects of thyroid state and beta adrenergic stimulation on mechanical restitution of rat ventricular myocardium Get access R BOTTINELLI, R BOTTINELLI From the Institute of Human Physiology, University of Pavia, Pavia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar C POGGESI, C POGGESI From the Institute of Human Physiology, University of Pavia, Pavia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar B POLLA, B POLLA From the Institute of Human Physiology, University of Pavia, Pavia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar C REGGIANI C REGGIANI From the Institute of Human Physiology, University of Pavia, Pavia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 597, https://doi.org/10.1093/cvr/22.8.597 Published: 01 August 1988
THE LOCATION AND NATURE OF ENTEROVIRUS RECEPTORS IN SUSCEPTIBLE CELLS
Authors: John J. Holland, Leroy C. McLaren
Journal: The Journal of Experimental Medicine (1961)

It is shown that enterovirus receptors are found mainly in the microsomal fraction of disrupted primate cells. Greater virus adsorption was exhibited by disrupted cells than by intact cells, indicating that enterovinis receptor may be present on intracellular membranes as well as on the surface of the cell. Polio-virus receptor is an integral part of, or is firmly attached to, the insoluble lipoproteins of the cell. All attempts to solubilize receptor have either destroyed virus-adsorbing activity, or have failed to separate it from sedimentable lipoproteins. The destruction of poliovirus receptor activity by proteolytic enzymes, surface active agents, organic solvents, concentrated urea solutions, phenol, formaldehyde, etc., all strongly indicate that this receptor function depends upon integrity of a protein portion of the membrane lipoproteins.
Liability Crisis or Insurance Problem?-Reply
Authors: Eugene I. Pavalon
Journal: JAMA (1987)

<h3>In Reply.—</h3> My suggestion to "cool the rhetoric" and seek sound workable solutions to the problem of excessive premiums for medical malpractice insurance had no effect on Dr Gillett. His letter contains the usual well-worn accusatory language about a "tort system out of control" and the equating of plaintiff's lawyers to "hired guns." Dr Gillett, as well as so many others in a profession that includes many of the best minds in our society, continues to ignore objective studies and empirical data that have been developed concerning the civil justice system generally and the root cause of the problem with malpractice insurance premiums specifically. Studies and data developed by objective entities such as the Urban Institute in Washington, DC,<sup>1</sup>The Rand Corporation,<sup>2</sup>The National Center for State Courts,<sup>3</sup>and most recently, the US General Accounting Office<sup>4</sup>all demonstrate that there is no "lawsuit crisis" and that
Effect of Antibacterial Home Cleaning and Handwashing Products on Infectious Disease Symptoms
Authors: Elaine L. Larson, Susan X. Lin, Cabilia Gomez-Pichardo, Phyllis Della-Latta
Journal: Annals of Internal Medicine (2004)

Background: Despite the widespread household use of cleaning and personal hygiene products containing antibacterial ingredients, their effects on the incidence of infectious disease symptoms have not been studied. Objective: To evaluate the effect of antibacterial cleaning and handwashing products for consumers on the occurrence of infectious disease symptoms in households. Design: Randomized, double-blind clinical trial. Setting: Northern Manhattan inner-city neighborhood, New York. Participants: 238 primarily Hispanic households (1178 persons) that included at least one preschool-age child. Interventions: Households were randomly assigned to use either antibacterial or nonantibacterial products for general cleaning, laundry, and handwashing. All products were commercially available, but the packaging was blinded and the products were provided free to participants. Measurements: Hygiene practices and infectious disease symptoms were monitored by weekly telephone calls, monthly home visits, and quarterly interviews for 48 weeks. Results: Symptoms were primarily respiratory: During 26.2% (717 of 2736) of household-months, 23.3% (640 of 2737) of household-months, and 10.2% (278 of 2737) of household-months, one or more members of the household had a runny nose, cough, or sore throat, respectively. Fever was present during 11% (301 of 2737) of household-months, vomiting was present in 2.2% (61 of 2737), diarrhea was present in 2.5% (69 of 2737), and boils or conjunctivitis were present in 0.77% (21 of 2737). Differences between intervention and control groups were not significant for any symptoms (all unadjusted and adjusted relative risks included 1.0) or for numbers of symptoms (overall incidence density ratio, 0.96 [95% CI, 0.82 to 1.12]). Conclusions: The tested antibacterial products did not reduce the risk for symptoms of viral infectious diseases in households that included essentially healthy persons. This does not preclude the potential contribution of these products to reducing symptoms of bacterial diseases in the home.
Rheumatoid Arthritis and Related Conditions
Authors: R. D. Sturrock
Journal: Annals of the Rheumatic Diseases (1980)

This method of presentation means that difficult to get an overall picture of a disea For example, the changes found in hyperti monary oesteoarthropathy may be found se the sections on the foot, the hand, and knee, b is there an overall description of the condil sequently one is left with the impression tha monest changes are a periostitis of the bc hand and feet, and the more common perio: forearms and ankles is not stressed.Similarly
8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes.
Authors: A M Shah, H A Spurgeon, S J Sollott, A Talo, E G Lakatta
Journal: Circulation Research (1994)

The role of cGMP in myocardial contraction is not established. Recent reports suggest that nitric oxide, released by endothelial cells or within myocytes, modifies myocardial contraction by raising cGMP. We studied the effects of 8-bromo-cGMP (8bcGMP, 50 mumol/L) on contraction (cell shortening) and simultaneous intracellular Ca2+ transients (indo 1 fluorescence ratio) in intact adult rat ventricular myocytes (0.5 Hz and 25 degrees C) 8bcGMP reduced myocyte twitch amplitude and time to peak shortening (-19.6 +/- 4.2% and -17.6 +/- 1.3%, respectively) and increased steady-state diastolic cell length (+0.6 +/- 0.1 microns, mean +/- SEM, n = 8; all P &lt; .05) but had no effect on shortening velocity, systolic or diastolic fluorescence ratio, or time to peak fluorescence ratio (all P = NS). In 7 of 13 myocytes, this negative inotropic effect was preceded by a transient positive inotropic effect, with small increases in twitch amplitude, shortening velocity, and cytosolic Ca2+ transient. Analysis of 8bcGMP effects on both the dynamic and steady-state relation between cell shortening and intracellular Ca2+ (during twitch contraction and tetanic contraction, respectively) indicated reduction in the myofilament response to Ca2+ in all cases. These 8bcGMP effects were inhibited by KT5823 (1 mumol/L), an inhibitor of cGMP-dependent protein kinase, or by the presence of isoproterenol (3 nmol/L). 8bcGMP had no effect on cytosolic pH in cells (n = 4) loaded with the fluorescent probe carboxyseminaphthorhodafluor-1. These data indicate that cGMP may modulate myocardial relaxation and diastolic tone by reducing the relative myofilament response to Ca2+, probably via cGMP-dependent protein kinase.
255. Preventing In Vivo Neurotoxicity Caused by HIV-1 Gp120 Using SV40 Vector Delivery of the Anti-Oxidant Enzymes Superoxide Dismutase and Glutathione Peroxidase
Authors: Lokesh Agrawal, Jean-Pierre Louboutin, Beverly A.S. Reyes, Elisabeth Van Bockstaele, David S. Strayer
Journal: Molecular Therapy (2006)

Symptomatic HIV-1 infection of the CNS is a common complication of systemic HIV-1 infection, and may vary in severity from mild motor neuron or cognitive impairment to frank dementia. HIV encephalopathy is largely caused by neuronal loss. HIV-1 envelope, gp120, induces free radical-mediated apoptosis of neurons. This phenomenon involves generation of reactive oxygen species (ROS), such as superoxide and peroxide, and may also involve other nitrogen-containing radicals, e.g., peroxynitrite (OONO). We hypothesized that neurons might be protected from such injury by gene delivery of anti-oxidant enzymes. To study this , we used recombinant SV40 derived vectors because they are highly efficient gene delivery vehicles for neurons. As antioxidant enzymes, superoxide-dismutase (SOD1) and glutathione peroxidase (GPx1) were used. We have established a small animal model system to study gp120-induced neuron apoptosis in rats. Both vectors SV(SOD1) and SV(GPx1) were injected once in vivo into the caudate putamen (CP) of the brain, to assess the effectiveness of rSV40 delivery of these antioxidant enzymes to the CNS. As assessed by Western blotting, enzyme activity assay and immunostaining, intracerebral injection of SV(SOD1) or SV(GPx1) into the CP resulted in excellent transgene expression 2 weeks and 4 weeks post-transduction. To elicit apoptosis with HIV-1 gp120, we performed dose-response and time course studies in which different amounts of gp120 were injected into the CP. Apoptosis, assayed by TUNEL, was maximal 24 hours after one injection of 500 ng gp120 (4.5 nmoles). By double staining, the preponderance of apoptotic cells were neurons. To test rSV40-delivered antioxidant protection, SV(SOD1) or SV(GPx1),or a control rSV40, was given 2 weeks before gp120 challenge. We observed gp120-induced apoptosis in high percentages of neurons from rats injected with control SV40 vectors. Transduction with SV(SOD1) or SV(GPx1) before gp120 challenge, reduced neuronal apoptosis by >80%. Currently we are testing the degree of protection in rat neurons after transduction with both the vectors in sequence. Thus SV(SOD1) and SV(GPx1) can be delivered by SV40 vectors in vivo, and they protect neurons from HIV-1 gp120-induced apoptosis. Because rSV40s have such high transduction efficiency for neurons and their delivery of antioxidant enzymes provides such effective mitigation of gp120-apoptosis, SV(SOD1) and SV(GPx1) may be useful both as investigative tools to elucidate mechanisms of neuron damage in HIV-1 infection in CNS and as potential paradigms for neuroprotective gene therapy strategies.
Cloning of the Murine Thymic Stromal Lymphopoietin (Tslp) Receptor
Authors: Linda S. Park, Unja Martin, Kirsten Garka, Brian Gliniak, James P. Di Santo, Werner Muller, David A. Largaespada, Neal G. Copeland, Nancy A. Jenkins, Andrew G. Farr, Steven F. Ziegler, Philip J. Morrissey, Raymond Paxton, John E. Sims
Journal: The Journal of Experimental Medicine (2000)

The cellular receptor for murine thymic stromal lymphopoietin (TSLP) was detected in a variety of murine, but not human myelomonocytic cell lines by radioligand binding. cDNA clones encoding the receptor were isolated from a murine T helper cell cDNA library. TSLP receptor (TSLPR) is a member of the hematopoietin receptor family. Transfection of TSLPR cDNA resulted in only low affinity binding. Cotransfection of the interleukin 7 (IL-7)Ralpha chain cDNA resulted in conversion to high affinity binding. TSLP did not activate cells from IL-7Ralpha(-/)- mice, but did activate cells from gammac(-/)- mice. Thus, the functional TSLPR requires the IL-7Ralpha chain, but not the gammac chain for signaling.
Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease
Authors: E. Clini, L. Bianchi, M. Pagani, N. Ambrosino
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity. <h3>METHODS</h3> Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV<sub>1</sub>) and the presence of cor pulmonale (CP) (group 1, FEV<sub>1</sub> &lt;35% predicted with CP, n = 15; group 2, FEV<sub>1</sub> &lt;35% predicted without CP, n = 15; group 3, FEV<sub>1</sub> &gt;35% predicted, n = 23). Seventeen normal subjects served as controls. <h3>RESULTS</h3> All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p&lt;0.01 ANOVA). In all subjects % predicted FEV<sub>1</sub> correlated slightly with PLNO but not with PNO. <h3>CONCLUSION</h3> Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.
Fatal Case of Necrotizing Enterocolitis Associated With Feeding Concentrated Infant Formula
Authors: George H. Nelson
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Infant formula can currently be purchased in cans that are either "ready-to-feed" or "concentrated liquid." The following case report emphasizes the critical importance of parents' understanding the difference between these two types of formula and following the directions as to dilution. <h3>Report of a Case.—</h3> The patient was a white female, the product of a term gestaton after an uneventful pregnancy, except for maternal hypertension at the time of delivery. The infant was delivered at a nearby local hospital; birth weight was 3,470 g, and Apgar scores were 9 and 10. The infant was fed formula and there was no record of vomiting or diarrhea in the nursery. At 3 days of age, weighing 3,429 g, and in good condition, she was discharged home with her mother. The mother was given some cans of formula with iron labeled "ready-to-feed" and was instructed to feed the formula undiluted.
Informed consent for elective surgery—what is best practice?
Authors: Owen A Anderson, I Mike J Wearne
Journal: Journal of the Royal Society of Medicine (2007)

Increasing medico-legal litigation,1 and the desire to provide patients with more say concerning their own treatment, has highlighted the issue of informed consent and how it is obtained. In order for a patient to make a sensible decision concerning his or her treatment they need appropriate information. This may occur via discussions with medical/nursing staff, via the media/internet, or from speaking with friends who have undergone a similar procedure. However, it chiefly occurs during the acquisition of informed consent, during which the risks and benefits of any surgical procedure are explained.

The principles of this paper are applicable to consent for any elective surgical procedure. However, we highlight examples from phacoemulsification cataract surgery, the most widely performed elective ophthalmic operation. This is an ideal example of elective surgery, as it can be performed with an equal outcome both early and late in the natural history of cataract, with the timing of surgery heavily reliant upon the patient's visual demands, anxieties and expectations. The discussion is focused predominately on UK Department of Health guidelines and English law, but many of the underlying ethical principles are still applicable to patients overseas.
Predictors of Job Satisfaction and Job Influence – Results from a National Sample of Swedish Nurses
Authors: I.-L. Petterson, B.B. Arnetz, J.E. Arnetz
Journal: Psychotherapy and Psychosomatics (1995)

Results from a questionnaire study on work conditions, job satisfaction, job influence, health and well-being, based on a representative sample of 3,500 Swedish nurses, indicate a high rate of overall job satisfaction. High decision latitude, consistency between work assignments and education, as well as low sickness absenteeism did all associate with high job satisfaction, number of working years did not. Compared to nurses satisfied with their jobs, twice as many sick days were found among those dissatisfied. Greater job influence related to lower job demands, more stimulating work and skills development as well as more responsibility and involvement. Anxiety and depression, intellectual satisfaction, job demands, job control and perceived general health explained 22% of the total variance in job satisfaction. The study has identified some key factors influencing overall job satisfaction. By focusing on these, job satisfaction among nurses should improve.
Cardiotrophin-1 induces sarcoplasmic reticulum Ca2+ leak and arrhythmogenesis in adult rat ventricular myocytes
Authors: Gema Ruiz-Hurtado, Nieves Gómez-Hurtado, María Fernández-Velasco, Eva Calderón, Tarik Smani, Antonio Ordoñez, Victoria Cachofeiro, Lisardo Boscá, Javier Díez, Ana María Gómez, Carmen Delgado
Journal: Cardiovascular Research (2012)

Plasma levels of cardiotrophin-1 (CT-1) are elevated in several cardiovascular diseases and are correlated with the severity of the pathology. However, the mechanisms by which this inflammatory cytokine participates in the pathology of the heart are not completely understood. It is well established that alterations in intracellular calcium ([Ca(2+)](i)) handling are involved in cardiac dysfunction during heart failure, but it is unknown whether CT-1 modulates [Ca(2+)](i) handling in adult cardiomyocytes. Here we have analyzed for the first time the effects of CT-1 on [Ca(2+)](i) homeostasis in adult rat cardiomyocytes.L-type calcium current (I(CaL)) was recorded using patch-clamp techniques, and [Ca(2+)](i) transients and Ca(2+) sparks were viewed by confocal microscopy. Treatment of cardiomyocytes with 1 nM CT-1 for 20-60 min induced a significant increase in I(CaL) density, [Ca(2+)](i) transients, and cell shortening compared with control cells. Our study reveals that CT-1 increases I(CaL) by a protein kinase A-dependent mechanism, and Ca(2+) sparks by a Ca(2+)/calmodulin kinase II-dependent and protein kinase A-independent mechanism. Cardiomyocytes treated with CT-1 exhibited a higher occurrence of arrhythmogenic behaviour, manifested as spontaneous Ca(2+) waves and aftercontractions.Our findings provide evidence that cardiomyocytes treated with CT-1 present high spontaneous Ca(2+) release during diastole, a mechanism linked to arrhythmogenicity in the pathologic heart.
Bone Scanning in Pregnant Patients with Breast Carcinoma
Authors: JAMES BAKER, AMJAD ALI, MARK W. GROCH, ERNEST FORDHAM, STEVEN G. ECONOMOU
Journal: Clinical Nuclear Medicine (1987)

Radionuclide scanning is usually contraindicated in pregnancy because of the danger of fetal radiation exposure. Radionuclide bone scanning with Tc–99m MDP is a sensitive indicator of early osseous metastases in breast cancer. Three cases of breast cancer during pregnancy are reported; modified bone scanning was utilized for staging and decision analysis. Modifications of bone scanning techniques to minimize fetal radiation exposure and fetal dosimetry calculations are described.
Native cellular fluorescence and its application to cancer prevention.
Authors: S P Schantz, H E Savage, P Sacks, R R Alfano
Journal: Environmental Health Perspectives (1997)

Native cellular fluorescence (NCF) represents the innate capacity of tissues to absorb and emit light of specified wavelengths. Recent advances in optical engineering and computer technology have provided the, opportunity to measure NCF characteristics of various tissues in vivo. This report will briefly review the current status of NCF analysis of various neoplastic tissues. The status of investigations involving the upper aerodigestive tract will be discussed. Though initial results demonstrate that neoplastic tissues can be discriminated from normal mucosa by NCF analysis, the biologic basis of this difference remains uncertain. This report will also emphasize that the ability to screen for cancer in aerodigestive mucosa may be enhanced through the assessment of multiple emission and excitation wavelengths. The true nature of the cellular fluorophores responsible for these mucosal spectral characteristics should be more fully defined in coming years.