tbuckley/cabot-search huggingface dataset:
Abstract 4894: Sorafenib enriches for sarcoma cancer stem cells <i>in vitro</i>.
Authors: Robert J. Canter, Erik Ames, Joseph Tellez, Rachel C. Smith, William J. Murphy
Journal: Cancer Research (2013)

Abstract Background: Cancer stem cells (CSCs) are a putative source of relapse in many cancers following anti-proliferative therapies. We hypothesized that tyrosine kinase inhibition (TKI) and radiotherapy (RT) would enrich for CSCs in sarcoma cell lines. Methods: A673 Ewing's sarcoma and SW982 synovial sarcoma cells were exposed to sorafenib and RT in a dose- and time-dependent fashion. Cultured cells were harvested and stained with fluorochrome-conjugated antibodies against human CSC markers including CD133, CD24, CD44, and aldehyde dehydrogenase (ALDH). Cell viability was analyzed using 7-Aminoactinomycin (7-AAD). Data were acquired using a BD Fortessa cell sorter (BD Biosciences) and analyzed with FlowJo software version 7.2. Parametric and non-parametric statistical tests were performed as appropriate. Results: Short-term exposure (≤1 day) to sorafenib demonstrated a linear dose-dependent cytotoxicity for A673 cells at doses ≥ 4 μM, while SW982 cells required doses ≥ 16 μM. At 24 hours, A673 cell viability decreased from 100% at 1 μM sorafenib to 0% at 32 μM (P&amp;lt;0.05). By day 5, A673 cells exposed to sorafenib doses &amp;lt; 32 μM recovered log-phase growth, while cells exposed to doses &amp;gt; 32 μM remained non-viable. Baseline CSC phenotyping of A673 cells demonstrated 55±5% CD133+, 12±7% ALDH+, 14% CD44+, and 0% CD24+ sub-populations. Baseline CSC phenotyping of SW982 cells demonstrated 0.2±0.9% CD133+, 42±8% ALDH+, 95±5% CD44+, and 40±7% CD24+. A673 cells exposed to 24h sorafenib increased the ALDH+ fraction to 40±3% (&amp;gt; 3-fold increase) at sorafenib 16 μM (P&amp;lt;0.05). SW982 cells showed a non-significant increase in the ALDH+ fraction at doses ≤ 16 μM. Although single fractions of RT were anti-proliferative to A673 cells starting at doses ≥5 Gy, there was not an additive effect of 2.5 Gy RT with sorafenib on cell viability or CSC marker expression. Conclusion: Sorafenib exerts an anti-proliferative effect on sarcoma cells but enriches for sarcoma CSC. The magnitude of these effects appears to be inversely correlated to baseline ALDH+ levels. Sustained anti-sarcoma therapeutic effects may require targeting of the CSC population following anti-proliferative therapy. Citation Format: Robert J. Canter, Erik Ames, Joseph Tellez, Rachel C. Smith, William J. Murphy. Sorafenib enriches for sarcoma cancer stem cells in vitro. [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 4894. doi:10.1158/1538-7445.AM2013-4894 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Acid sensing in renal epithelial cells
Authors: Stephen L. Gluck
Journal: Journal of Clinical Investigation (2004)

The kidney adjusts net acid excretion to match production with exquisite precision, despite little or no change in the plasma bicarbonate concentration. The acid-sensing pathway that signals the kidney to increase acid secretion involves activation of the proto-oncogene c-Src. A new study in this issue shows that proline-rich tyrosine kinase 2 (Pyk2) is responsible for acid-induced activation of c-Src and is essential for acid sensing in renal epithelial cells. The findings implicate a broader role for Pyk2 in acid-base homeostasis in bone and other tissues beyond the kidney.
Externalizing and internalizing behavioural problems related to asthma in school children
Authors: I. Annesi-Maesano, C. Zhou, N. Baïz, S. Banerjee, D. André Charpin, D. Caillaud, F. de Blay, C. Raherison, F. Lavaud
Journal: Allergy (2013)

We investigated the relationships of behavioural problems as assessed using the standardized Strengths and Difficulties Questionnaire (SDQ) to asthma in view of improving asthma management. Six thousand eight hundred and eighty children (mean age 10.4 years, male: 49%) were recruited in the French 6 Cities Study. Children with abnormal or borderline emotional symptoms (internalizing problems) or conduct problems (externalizing problems) were more asthmatic than others (P < 0.01). Compared to being normal, abnormal emotional symptoms or conduct problems were found to be related to mild-to-moderate persistent asthma (logistic model adjusted odds ratio = 1.55 (95% CI = 1.26–1.90) and 1.42 (95% CI = 1.17–1.71), respectively) and to early-onset asthma (Cox's model Adjusted Hazard Risk = 1.60 (95% CI = 1.27–2.01) and 1.34 (95% CI = 1.05–1.70). Borderline conduct problems were found to be negatively related to parents' knowledge on how to prevent asthma attacks, compared to normal conduct problems [adjusted OR = 0.51 (95% CI = 0.31–0.85)]. Further data are needed to better understand the involvement of behavioural problems in childhood asthma according to phenotypes.
Solving the Medical Care Dilemma
Authors: Philip Caper
Journal: New England Journal of Medicine (1988)

THE United States spends more on medical care — both in absolute terms and as a percentage of its gross national product — than any other industrialized nation. American medical care is unsurpassed in technological sophistication, but its costs are very high and rising rapidly. The panoply of cost-containment programs developed over the past decade has had little effect on overall expenditures, but it has had serious consequences in other areas.As government and private purchasers of health insurance constrict benefit packages and restrict criteria for eligibility, a record number of Americans are squeezed out of our health insurance system. . . .
Health Locus of Control: A Potential Moderator Variable for the Relationship between Life Stress and Psychopathology
Authors: Nancy L. Hutner, Steven E. Locke
Journal: Psychotherapy and Psychosomatics (1984)

Although research indicates that stressful life events commonly precede the onset of a variety of psychological disorders, reported correlations have consistently been only moderately strong. The present study examined the possibility that the health locus of control (HLC) mediates the relationship between life event stress and psychopathology. Subjects were 81 male volunteers between the ages of 21 and 62. The SCL-90-R was utilized to measure psychological symptom status. Subjects' perceptions regarding the desirability and controllability of experienced events were examined. Life events which were perceived to be both undesirable and uncontrollable were significantly correlated with the indices of psychopathology only for subjects who were external in HLC. Externals also showed significant correlations between events which were perceived as being undesirable but under personal control and psychological symptoms. The results suggest that externals are more vulnerable to life event stress than internals. Practical implications for health psychologists are discussed.
Residential Traffic and Children’s Respiratory Health
Authors: Janice J. Kim, Karen Huen, Sara Adams, Svetlana Smorodinsky, Abby Hoats, Brian Malig, Michael Lipsett, Bart Ostro
Journal: Environmental Health Perspectives (2008)

BackgroundLiving near traffic has been associated with asthma and other respiratory symptoms. Most studies, however, have been conducted in areas with high background levels of ambient air pollution, making it challenging to isolate an independent effect of traffic. Additionally, most investigations have used surrogates of exposure, and few have measured traffic pollutants directly as part of the study.ObjectiveWe conducted a cross-sectional study of current asthma and other respiratory symptoms in children (n = 1,080) living at varying distances from high-traffic roads in the San Francisco Bay Area, California, a highly urbanized region characterized by good regional air quality due to coastal breezes.MethodsWe obtained health information and home environmental factors by parental questionnaire. We assessed exposure with several measures of residential proximity to traffic calculated using geographic information systems, including traffic within a given radius and distance to major roads. We also measured traffic-related pollutants (nitrogen oxides and nitrogen dioxide) for a subset of households to determine how well traffic metrics correlated with measured traffic pollutants.ResultsUsing multivariate logistic regression analyses, we found associations between current asthma and residential proximity to traffic. For several traffic metrics, children whose residences were in the highest quintile of exposure had approximately twice the adjusted odds of current asthma (i.e., asthma episode in the preceeding 12 months) compared with children whose residences were within the lowest quintile. The highest risks were among those living within 75 m of a freeway/highway. Most traffic metrics correlated moderately well with actual pollutant measurements.ConclusionOur findings provide evidence that even in an area with good regional air quality, proximity to traffic is associated with adverse respiratory health effects in children.
Myocyte Enhancer Binding Factor-2 Expression and Activity in Vascular Smooth Muscle Cells
Authors: Anthony B. Firulli, Joseph M. Miano, Weizhen Bi, A. Daniel Johnson, Ward Casscells, Eric N. Olson, John J. Schwarz
Journal: Circulation Research (1996)

Abstract Proliferation and phenotypic modulation of smooth muscle cells (SMCs) are major components of the vessel’s response to injury in experimental models of restenosis. Some of the growth factors involved in restenosis have been identified, but to date little is known about the transcription factors that ultimately regulate this process. We examined the expression of the four members of the myocyte enhancer binding factor-2 (MEF2) family of transcription factors in cultured rat aortic SMCs (RASMCs) and a rat model of restenosis because of their known importance in regulating the differentiated phenotype of skeletal and cardiac muscle. In skeletal and cardiac muscle, the MEF2s are believed to be important for activating the expression of contractile protein and other muscle-specific genes. Therefore, we anticipated that the MEF2s would be expressed at high levels in medial SMCs that are producing contractile proteins and that they would be downregulated along with the contractile protein genes in neointimal SMCs. On the contrary, we observe that MEF2A, MEF2B, and MEF2D mRNAs are upregulated in the neointima, with the highest levels in the layer of cells nearest to the lumen, whereas MEF2C mRNA levels do not appreciably increase. Moreover, few cells in the media are making MEF2 proteins detectable by immunohistochemistry, whereas large numbers of neointimal cells are positive for all four MEF2s. These data suggest that the MEF2s are involved in the activated smooth muscle phenotype and not in the maintenance of contractile protein gene expression.
A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions
Authors: Lydia E. Pace, Nancy L. Keating
Journal: JAMA (2014)

<h3>Importance</h3> Breast cancer is the second leading cause of cancer deaths among US women. Mammography screening may be associated with reduced breast cancer mortality but can also cause harm. Guidelines recommend individualizing screening decisions, particularly for younger women. <h3>Objectives</h3> We reviewed the evidence on the mortality benefit and chief harms of mammography screening and what is known about how to individualize mammography screening decisions, including communicating risks and benefits to patients. <h3>Evidence Acquisition</h3> We searched MEDLINE from 1960-2014 to describe (1) benefits of mammography, (2) harms of mammography, and (3) individualizing screening decisions and promoting informed decision making. We also manually searched reference lists of key articles retrieved, selected reviews, meta-analyses, and practice recommendations. We rated the level of evidence using the American Heart Association guidelines. <h3>Results</h3> Mammography screening is associated with a 19% overall reduction of breast cancer mortality (approximately 15% for women in their 40s and 32% for women in their 60s). For a 40- or 50-year-old woman undergoing 10 years of annual mammograms, the cumulative risk of a false-positive result is about 61%. About 19% of the cancers diagnosed during that 10-year period would not have become clinically apparent without screening (overdiagnosis), although there is uncertainty about this estimate. The net benefit of screening depends greatly on baseline breast cancer risk, which should be incorporated into screening decisions. Decision aids have the potential to help patients integrate information about risks and benefits with their own values and priorities, although they are not yet widely available for use in clinical practice. <h3>Conclusions and Relevance</h3> To maximize the benefit of mammography screening, decisions should be individualized based on patients' risk profiles and preferences. Risk models and decision aids are useful tools, but more research is needed to optimize these and to further quantify overdiagnosis. Research should also explore other breast cancer screening strategies.
A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases: Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab
Authors: Jonathan W. Riess, Seema Nagpal, Millie Das, Joel W. Neal, Jonathan W. Kim, Heather A. Wakelee
Journal: Journal of Thoracic Oncology (2013)
Depressed Adenyl Cyclase Activity in the Failing Guinea Pig Heart
Authors: B. E. SOBEL, P. D. HENRY, A. ROBISON, C. BLOOR, J. ROSS
Journal: Circulation Research (1969)

There is considerable evidence that several effects of catecholamines on beta receptors, including the positive inotropic effect on the heart, are mediated by cyclic-AMP.Myocardial cyclic-AMP concentration depends on the activity of at least two enzymes: adenyl cyclase, regulating synthesis, and phosphodiesterase, regulating degradation of the compound.In view of the importance of adrenergic support in maintaining cardiac performance, we examined synthesis and degradation of cyclic-AMP in homogenates of hearts from guinea pigs with congestive heart failure produced by constriction of the ascending aorta and from sham-operated controls.In the experimental group, left ventricular weight, DNA, RNA, and protein content were significantly increased 7 to 12 days following operation, and congestive heart failure developed, manifested by hydrothorax, hepatomegaly, and histologic evidence of pulmonary edema and passive congestion of viscera.Adenyl cyclase activity in homogenates from the experimental group was 36% less than that observed in controls ( P < 0.001).However, phosphodiesterase activity was unchanged.These findings suggest that there is a double biochemical defect in the adrenergic support to the failing heart.In addition to the known reduction of myocardial catecholamines, there appears to be diminished capacity for synthesis of cyclic-AMP, an important mediator of catecholamine action. ADDITIONAL KEY WORDS catecholamines myocardial contractility cyclic-AMP experimental heart failure effects on beta receptors• There is considerable evidence suggesting that the positive inotropic action of catecholamines provides an important reserve mechanism in the regulation of cardiac performance (1, 2).It is clear that effects of catecholamines on beta receptors, such as glycogenolysis in the heart and lipolysis in adipose tissue, are mediated by a "secondary intracellular messenger," 3',5'-adenosinemonophosphate (cyclic-AMP) (3).Furthermore, it appears that the positive inotropic effect of catecholamines on the heart, another effect on beta receptors, may be mediated by cyclic-AMP (4, 5), although this has not been established
Peripheral Unresponsiveness to Human Growth Hormone in Laron Dwarfism
Authors: David W. Golde, Noelle Bersch, Solomon A. Kaplan, David L. Rimoin, Choh Hao Li
Journal: New England Journal of Medicine (1980)

IN 1966 Laron and his associates described a severe form of dwarfism associated with high levels of circulating immunoreactive human growth hormone.1 Laron dwarfism is usually a familial disorder, and affected persons are generally resistant to the effects of endogenous or exogenous growth hormone.2 3 4 5 6 7 Current evidence suggests that the circulating growth hormone in Laron dwarfs is immunochemically and biochemically normal.7 8 9 Furthermore, Jacobs et al. have found that the endogenous growth hormone in affected persons binds normally in radioreceptor assays.10 It has therefore been postulated, but not demonstrated, that the syndrome of Laron dwarfism is due to end-organ unresponsiveness to growth . . .
Whole Brain Segmentation
Authors: Bruce Fischl, David H. Salat, Evelina Busa, Marilyn Albert, Megan Dieterich, Christian Haselgrove, Andre van der Kouwe, Ron Killiany, David Kennedy, Shuna Klaveness, Albert Montillo, Nikos Makris, Bruce Rosen, Anders M. Dale
Journal: Neuron (2002)
A Study of Renal Function in Orthostatic Hypotension
Authors: ERLING KRUGE BRODWALL
Journal: Circulation (1960)

Renal function studies have been carried out in both the recumbent and in the oblique position in 2 cases of orthostatic hypotension. In both cases a definite fall in plasma flow and glomerular filtration rate took place, but this occurred only after registration of a considerable fall in blood pressure. The filtration fraction remains unchanged after the fall in blood pressure. The extraction ratio remains unchanged after a considerable fall in blood pressure. The data may indicate that the renal function becomes normal if blood pressure is kept on a low level over a fairly long period. However, further observations are required before any definite conclusion may be drawn.
Some Thoughts upon the Discontents of the British General Practitioner
Authors: Peter C. Whybrow
Journal: New England Journal of Medicine (1967)

SINCE my arrival in the United States approximately eighteen months ago, I have frequently been asked for my views upon the British system of "socialized medicine." This in itself, of course, was no surprise, but I have been increasingly impressed during my discussions by the many erroneous notions held by seemingly well informed persons, both colleagues and lay friends.There is frequently a suggestion that the recent problems of the British general practitioner, amply covered in the American press, are entirely a product of the National Health Service and, further, that if the Service had not been introduced eighteen years . . .
The Care of the Patient
Authors: Maurice B. Strauss
Journal: JAMA (1969)

<h3>To the Editor:—</h3> I was quite surprised to find the statement about the secret of caring for the patient attributed to Osler (<b>209</b>:1068, 1969). InThe Journal(<b>88</b>:877, 1927), Francis Weld Peabody, MD, of the Thorndike Memorial Laboratory in the Boston City Hospital, wrote on "The Care of the Patient." The final sentence reads: "One of the essential qualities of the clinician is an interest in humanity, for the secret of the care of the patient is in caring for the patient." I would suspect that Osler may have had the same thought, but that the statement was Dr. Peabody's.
(18F)fluorodeoxyglucose (FDG) positron emission tomography (PET) and neuropsychological study before and after liver transplantation (OLT)
Authors: P. Burra, G. Pizzolato, F. Chierichetti, U. Tedeschi, R. D'Inca', S. Fagiuoli, A. Floreani, G. Pittoni, M. Dam
Journal: Journal of Hepatology (1998)
Matching Wits with Melanoma Brain Metastases: From Biology to Therapeutics
Authors: Hussein Tawbi
Journal: Clinical Cancer Research (2014)

Melanoma brain metastases (MBM) present a significant clinical challenge. Molecular profiling of MBM is useful to identify molecular pathways, such as the PI3K pathway, that are specifically and differentially altered in MBM. Therapeutic studies should recruit patients with MBM and prospective tissue collection will lay the foundation for further advances.
PTH-070 Endoscopic Resection of Giant, (> 4Cm) Sessile/Flat Colonic Polyps: Techniques and outcomes
Authors: Z P Tsiamoulos, S T Peake, N Suzuki, L A Bourikas, J Warusavitarne, B P Saunders
Journal: Gut (2013)

<h3>Introduction</h3> Giant, sessile/flat colon polyps (&gt; 4cm) are challenging to remove endoscopically and many lesions are still treated with laparoscopic or open segmental resection. <h3>Methods</h3> From our prospective, tertiary referral, polypectomy database of large colorectal polyps, 107/297 consecutive patients with 109/316 colon polyps, were referred for endoscopic resection of &gt; 4cm flat/sessile colon polyps with a mean size (± SD), 52 ± 22mm. Reasons for tertiary referrals were large polyp size/extent with moderate to severe submucosal fibrosis (SF) (37%), difficult endoscopic access (36%) or failure to adequately lift (24%). Polyps were assessed and treated using ‘inject and cut’ piecemeal Endoscopic Mucosal Resection (P-EMR) or P-EMR with Endoscopic Mucosal Ablation (P-EMR/EMA). Supplementary techniques such as Endocuff-assisted polypectomy (EAP) and Laparoscopic-assisted endoscopic polypectomy (LAP) were employed to improve endoscopic access. Completion rates, recurrence, and adverse events were documented prospectively. <h3>Results</h3> Nineteen P-EMR/EMA hybrids, 29 Spiral snare (Olympus) P-EMR’s and 2 EAP’s were performed to treat polyps with SF (42% previously failed polypectomy attempt at referring centre, 7.5% tattoo under polyp and 51.5% lesion-related fibrosis) and improve endoscopic access. Polypectomy was considered successful in 94.5% in a single session with mean procedure time (± SD), 43 ± 12.2 min. One deep submucosal tear (0.9%) was successfully treated with endoclips. Eight patients (7.4%) required hospitalisation due to delayed post-polypectomy bleeding with one undergoing emergency laparotomy. There was no mortality. First follow up (3/6 months) was attended by 92/107 patients with no recurrence in 41/92 (3 malignant polyps favourable histology), easily treatable benign recurrence of &lt; 10mm in 39/92 and &gt; 10mm recurrence in 12/92 (one patient with large rectal recurrence had a TEMS procedure and two patients with histology showing malignancy had segmental resections). A second f/u (9/15 months post initial resection) was performed in 40/92 patients with no recurrence in 28/40, &lt; 10 mm benign recurrence in 11/42 (continuing surveillance) and one benign recurrence &gt; 10mm (continuing surveillance). <h3>Conclusion</h3> Endoscopic resection of giant, &gt; 4cm, sessile/flat colon polyps demands a multi-modality approach, but good medium term outcomes can be achieved with most patients spared surgery. Minor recurrence occurs frequently but can be successfully managed with close surveillance. <h3>Disclosure of Interest</h3> None Declared.
Long-Term Oxygen Therapy
Authors: N. R. ANTHONISEN
Journal: Annals of Internal Medicine (1983)

The status of long-term, outpatient oxygen therapy is reviewed, particularly as it is applied to patients with chronic obstructive pulmonary disease. Recent clinical trials have shown that in stable hypoxemic patients (arterial O2 tension less than 60 torr) with obstructive disease, survival is prolonged by chronic O2 therapy, and that the more continuous the therapy is, the better the survival rate. The mechanism of the improved survival rate is not clear, although O2 therapy decreases the hematocrit and pulmonary vascular resistance and may improve neuropsychological function. In such patients, nocturnal decreases in arterial O2 saturation are associated with carbon dioxide retention and may contribute to pulmonary hypertension. Nocturnal hypoxemia is eliminated by the usual continuous O2 therapy. The incidence of nocturnal hypoxemia without upper airway obstruction or daytime hypoxemia is not known but may be small. Nocturnal O2 treatment for such patients may be indicated, but further studies are needed. Oxygen therapy during exercise in patients who are not hypoxemic at rest should be done only when benefits cannot be attributed to a placebo effect of O2 therapy.