tbuckley/cabot-search huggingface dataset:
Characterization of side-population cells in normal neural and brain cancer stem cells
Authors: Molly Harris, Hyuna Yang, Kyuson Yun
Journal: Cancer Research (2007)

1301   Recent identification of cancer stem cells from multiple solid and blood tumors challenges us to rethink the biology and treatment strategies for human cancer. Mouse models of human cancer have been successfully used in numerous studies to gain insights into cancer biology. We have previously reported that mouse models of spontaneous oligodendroglioma contain cancer stem cells, indicating that mouse models can be used to study this important cell type in vivo. In this study, we report further characterization of these cells at molecular and cellular levels to understand distinguishing features of normal and transformed stem cells and to identify genetic alterations that may trigger cellular transformation of stem cells.  First, we describe cellular differences between normal and cancer stem cells, in terms of their growth-factor dependence, cell surface antigen expression, and morphology. In particular, we show that mouse brain tumor stem cells contain both CD133+ and side-population (SP) cells, and that SP is enriched in tumor-initiating cells. SP is identified by a cellular phenotype that is defined by the ability of stem cells to extrude Hoechst 44432 dye. Side population constitutes approximately 1% of our cultured cells (both in normal neural and brain tumor stem cell cultures). When SP cells from tumor cultures are injected, as few as 50 cells can initiate a tumor in NOD-SCID mice while as many as 50,000 non side-population cells from the same culture do not.  Second, to understand underlying molecular differences between normal and transformed stem cells, we purified side-population cells from normal and cancer stem cell cultures and examined gene expression profiles using Affymetrix MOE430v2 microarrays. This approach was designed to minimize the noise inherent in gene expression studies by 1) taking advantage of the identical genetic background in inbred strain of mice from which these cells were isolated, and 2) extracting RNA only from cells that are in equivalent cellular state by isolating SP cells. With the q-value set at
Metabolism of adrenal cholesterol in man
Authors: Abraham Borkowski, Claude Delcroix, Sam Levin
Journal: Journal of Clinical Investigation (1972)

The kinetics of plasma and adrenal cholesteral equilibration were analyzed in patients undergoing bilateral adrenalectomy for generalized mammary carcinoma. A biological model is proposed to help in the understanding of adrenal cholesterol physiology. It comprises two intracellular compartments: (1) A compartment of free adrenal cholesterol which is small (of the order of 17 mg) but turns over very fast; it is renewed approximately 8 times per day: 3 times by the inflow of free plasma cholesterol, and 5 times by the hydrolysis of esterified adrenal cholesterol, the contribution of adrenal cholesterol synthesis appearing to be relatively small. (2) A compartment of esterified adrenal cholesterol which is 20 times larger; it is constantly renewed by in situ esterification and hydrolysis with a daily fractional turnover rate of the order of 0.25. The direct and selective accumulation of plasma cholesteryl esters is practically absent. Only free adrenal cholesterol returns to plasma, mostly after conversion into steroid "hormones."However small the synthesis of adrenal cholesterol may be, it seems more important in the zona "reticularis." On the other hand, the inflow of plasma cholesterol and the turnover of the free adrenal compartment tend to be faster in the zona "fasciculata." The equilibration of plasma and adrenal cholesterol can proceed unmodified under conditions of ACTH suppression. In one patient with Cushing's disease the size of the two adrenal compartments was clearly increased but their equilibration with plasma cholesterol proceeded normally. In another patient the kinetics of hydrocortisone corresponded to those of free adrenal cholesterol in the control studies.
Abstract 18105: Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure
Authors: Guangming Cheng, Magdy Girgis, Arash Davani, Yanjuan Yang, Harold Elias, Lei Chen, Jeryl Hauptman, Robert J Vincent, Buddhadeb Dawn
Journal: Circulation (2013)

Increasing evidence indicates a role of proinflammatory cytokines in the pathogenesis of myocardial hypertrophy and failure. Chronic interleukin-6 (IL-6) stimulation leads to LV hypertrophy and dysfunction, and deletion of IL-6 reduces LV hypertrophy after angiotensin II infusion. In this study, we tested the hypothesis that genetic deletion of IL-6 would ameliorate pressure overload-induced myocardial hypertrophy and failure. We performed transverse aortic constriction (TAC) in IL-6 knockout (IL6 KO) mice and wild-type (WT) C57BL/6J mice (control) to induce pressure overload. Cardiac structure and function were assessed by serial echocardiography prior to and until 42 days after TAC. Pressure overload induced progressive LV hypertrophy, remodeling, and dysfunction in WT control mice compared with baseline (BSL) (Figure). At 6 wks after TAC, these adverse effects of pressure overload were significantly attenuated in IL6 KO mice, as evidenced by smaller LV mass and greater LV EF compared with controls (Figure). We conclude that genetic deletion of IL-6 attenuates LV remodeling and dysfunction induced by pressure overload. These data suggest a possible therapeutic potential of IL-6 inhibition to ameliorate LV hypertrophy and dysfunction in patients with systemic hypertension.
Assessment of public health issues of migrants at the Greek-Turkish border, April 2011
Authors: E Mertens, G Rockenschaub, A Economopoulou, P Kreidl
Journal: Eurosurveillance (2012)

A joint mission to assess the public health situation of migrants in Greek detention centres was undertaken in April 2011 by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) Regional Office for Europe. The assessment visit follows the increased migration to the Evros prefecture, Eastern Macedonia and Thrace region, at the Greek-Turkish border where large numbers of migrants are entering Greece via the Evros River, a natural border. Migrants are housed in local detention centres. The main problem in detention centres are the substandard hygiene conditions, especially overcrowding and lack of personal hygiene facilities, lack of basic supplies and lack of access to fresh air and physical exercise. As the migration route via the Evros region is increasingly used since 2009, and due to the unstable political situation in North Africa and the Middle East, an increased influx of migrants was to be expected with the falling water levels of the Evros River in summer, resulting in further deterioration of the already critical situation in the Thrace region’s detention centres.
Abstract 1645: Relationship of Premature Family History of Coronary Heart Disease With Coronary Artery Calcium Progression in the Multi-Ethnic Study of Atherosclerosis
Authors: Kavita Sharma, Juan J Rivera, Matthew J Budoff, Ron Blankstein, Mouaz H Al-Mallah, Nathan D Wong, Leslee J Shaw, Jeffrey Carr, Daniel O'Leary, Joao A Lima, Moyses Szklo, Roger S Blumenthal, Khurram Nasir
Journal: Circulation (2009)

Background: A family history (FamHx) of premature coronary heart disease (CHD) is an independent risk factor for CHD events. In this study we aimed to assess whether FamHx of both premature and lat...
Increased Expression of Adenosine Triphosphate-Sensitive K+ Channels in Mitral Dysfunction
Authors: Véronique Raeis-Dauvé, Pierre Philip-Couderc, Giuseppe Faggian, Maddalena Tessari, Angela Roatti, Aldo D. Milano, Marie-Luce Bochaton-Piallat, Alex J. Baertschi
Journal: Journal of the American College of Cardiology (2011)
Abstract 12694: The Mechanistic Link Between Interatrial Adiposity, Morphological Left Atrial Remodeling and Functional Features in Asymptomatic Population
Authors: Yau-Huei Lai, Chun-Ho Yun, Jen-Yuan Kuo, Jia-Yin Hou, Hung-I Yeh, Chung-Lieh Hung
Journal: Circulation (2014)

Introduction: Left atrial (LA) mechanics play a key role in heart failure (HF) development and atrial fibrillation. So far, the pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. However, the precise mechanisms between regional fat and LA remodeling in asymptomatic population remains largely unexplored. Hypothesis: We hypothesize that LA function is negatively affected by pericardial fat burden. Methods: We studied 361 consecutive subjects (age: 51.8+/- 8.8, 31% female) free from significant valvular disorders, atrial fibrillation and clinical HF. Regional visceral adiposity including total pericardial fat (PCF) and thoracic periaortic fat (TPAF) volumes, interatrial septum (IAS) and left atrioventricular groove (AVG) fat thickness were all obtained by multidetector computed tomography (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). LA volumes, contractile performance and reservoir function as well as conduit capacity were all measured by echocardiography. Results: All four adiposity measures (PCF, TPAF, AVG and IAS) were associated with larger LA volume indices (all p&lt;0.05). Furthermore, IAS and AVG were related to larger LA kinetic energy and worse reservoir capacity (both p&lt;0.05). In multivariate models, IAS fat thickness remained independently associated with increased LA conduit function (β-coef: 0.28), ejection force (β-coef: 0.15) and impaired LA reservoir function (β-coef: -0.20, all p&lt;0.05), even after adjusting for clinical variables. Conclusions: Accumulated visceral adiposity, especially interatrial fat depots, may be partially associated with LA structural and functional remodeling, which is characterized by impaired LA reservoir capacity, augmented contractile and conduit performance. Our data suggested that compensatory LA mechanistic adaptation with greater visceral fat burden may exist in asymptomatic population.
Abstract 17312: Amyloid-β (1-40) and the Risk of Death from Cardiovascular Causes in Patients with Coronary Heart Disease
Authors: Kimon Stamatelopoulos, Dirk Sibbing, Loukianos S Rallidis, Georgios Georgiopoulos, Dimitrios Stakos, Siegmund Braun, Aikaterini Gatsiou, Kateryna Sopova, Christos Kotakos, Christos Varounis, Costantinos C Tellis, Efstathios Kastritis, Maria Alevizaki, Alexandros D Tselepis, Panagiotis Alexopoulos, Christoph Laske, Till Keller, Adnan Kastrati, Stefanie Dimmeler, Andreas M Zeiher, Konstantinos Stellos
Journal: Circulation (2014)

Introduction: Investigation of the clinical value of biologic pathways that are involved in pathogenesis of atherosclerotic disease is essential for identification of novel therapeutic targets and improvement of cardiovascular risk stratification. Hypothesis: To determine the clinical value of amyloid-β 1-40 (Aβ40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. Methods: Aβ40 was retrospectively measured in blood samples collected from three independent prospective cohorts and two case-control cohorts (total n=1464). Major adverse CV events (MACE) were assessed in the two prospective cohorts (n=877) followed for a median of 4.4 years. Arterial stiffness was evaluated at baseline and after a 5-year follow-up period (n=107) in young healthy subjects. The primary endpoint was the predictive value of Aβ40 for CV mortality and outcomes in patients with CHD. Further, the associations of Aβ40 levels with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD were addressed. Results: In Cox proportional-hazards models adjusted for age, gender, glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein and high-sensitivity troponin-T, Aβ40 was an independent predictor of CV death and MACE in patients with CHD (P&lt;0.05 for all). After multivariate adjustment, Aβ40 levels conferred a substantial enhancement of net reclassification index (continuous NRI value and 95% confidence interval: 36.7%, 12.5-60.7, P=0.001) and integrated discrimination improvement (IDI value±SE: 1.92±0.62, P&lt;0.001) of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Aβ40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD. Conclusions: Measuring blood levels of Aβ40 identifies patients at high risk for cardiovascular death.
Clinical experience and performance in final examinations
Authors: W.-C. Leung, B. Jolly, E. Murray, C. McManus, B. Winder, P. Richards
Journal: BMJ (1998)

Editor—McManus et al found that their prospective study of two cohorts of medical students at a London medical school showed that the students’ learning style, but not their final examination results, was related to the amount of knowledge gained from clinical experience.1

Their questionnaire measured some aspects of the students’ clinical exposure but did not measure the knowledge gained from such experience.2 A proportion of the practical procedures and surgical operations selected in the questionnaire was not of central relevance to undergraduates, even after the time when the study was carried out is taken into account. Students should never have performed procedures such as colonoscopy, abdominal paracentesis, ring block, endotracheal intubation, and intramuscular or subcutaneous injection without supervision, even in the early 1990s. 

Likewise, having seen operations such as laryngectomy, removal of cerebral tumour, or skin grafting more than four times was less relevant than developing a systematic approach to the diagnosis and management of common symptoms. It is this systematic approach that final examinations assess. Furthermore, even if the authors’ measurements of clinical experience were valid, the association of learning style with clinical experience was small (for 1986 cohort, deep learning, r=0.26, r2=0.07). 

The authors concluded that medical schools could select students by assessing their learning styles. This might lead to profit making organisations offering courses on completing questionnaires on learning styles. The reliability and validity of the assessment of learning style with a questionnaire would decrease if it were carried out under such threatening conditions, as the candidates might respond to the questionnaires according to their perception of what medical schools regard as desirable. 

Students adapt their learning strategies to the perceived demands of lecturers and departments.3 Furthermore, having a match between styles of learning and teaching has been shown to be even more important than the particular learning style adopted by the student.4,5 A more constructive and effective approach would be for teachers and departments to review their own teaching styles and to identify and help students with an inappropriate learning style.
Lipid rafts/caveolae disruption induces HIF-1a expression via EGFR activation for anoikis regulation.
Authors: Seong-Hee Lee, Jong Wan Park, Sang-Kyu Ye, Jong Bae Park, Byung-Kiu Park, Yong-Nyun Kim
Journal: Cancer Research (2008)

3406  The plasma membrane is comprised of lipid rafts/caveolae domains that are essentially organizing sites of multiple signaling pathways that are involved in regulation of cellular functions such as cell survival and adhesion. Cholesterol is a critical component of lipid rafts/caveoale in terms of their integrity and function. We have reported that raft disruption by cholesterol depletion by methyl-beta cyclodextrin (MBCD) induces anoikis-like cell death although EGFR is activated. HIF-1a is known to be up-regulated by oxygen-independent pathways, such as EGFR activation. Here, we examined a possible association of EGFR activation and HIF-1a with anoikis induced by raft disruption. MBCD treatment resulted in HIF-1 protein up-regulation in dose and time-dependent manner. MBCD treatment induced activations of multiple proteins, including EGFR, Src, ERK1&2, p38, but not Akt. EGFR activation appeared to be critical for HIF-1 up-regulation and VEGF secretion upon MBCD treatment. Si-HIF1-a enhanced cell detachment and decreased cell viability in MBCD treated cells. These data indicate that raft/cholesterol level can regulate HIF-1 levels which is important for anoikis regulation.
Abstract 5393: Increased C-Reactive Protein Expression Exacerbates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction
Authors: Toshiyuki Takahashi, Toshihisa Anzai, Hidehiro Kaneko, Atsushi Anzai, Yoshinori Mano, Yuichiro Maekawa, Satoshi Ogawa, Tsutomu Yoshikawa
Journal: Circulation (2008)

We have previously reported that elevated serum C-reactive protein (CRP) level after acute myocardial infarction (MI) is associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling and cardiac death. Recent experimental studies have shown that CRP per se has some biological properties including proinflammatory and proapoptotic effects, suggesting a pathogenetic role of CRP in the remodeling process after MI. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI through some deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their nontransgenic littermates (Control) underwent proximal ligation of the left coronary artery. Despite increased serum CRP level and cardiac CRP expression in CRP-Tg mice, there was no difference in phenotype between CRP-Tg and control mice before MI. Mortality at five weeks after MI was not different between groups (CRP-Tg: 49%, n=35; Control: 38%, n=40, P =0.28). Five weeks after MI, echocardiography showed that CRP-Tg mice had more LV dilation (LVEDD, CRP-Tg: 5.8 ± 0.1 mm, n=14; Control: 5.2 ± 0.1 mm, n=17, P =0.002) and worse LV function (EF, CRP-Tg: 13 ± 2%, n=14; Control: 19 ± 1%, n=17, P =0.01). Hemodynamic studies indicated that LV +dP/dt (CRP-Tg: 2,947 ± 480 mmHg/s, n=9; Control: 3,788 ± 656 mmHg/s, n=10, P =0.02) and -dP/dt (CRP-Tg: −2,230 ± 48 mmHg/s, n=9; Control: −2,890 ± 161 mmHg/s, n=10, P =0.003) were lower in the CRP-Tg group than in the Control group, although infarct size was comparable. Histological evaluation at one week after MI showed a higher rate of apoptosis in the border zone of infarcted hearts from CRP-Tg mice (CRP-Tg: 1,434 ± 322 per 10 5 nuclei; Control: 596 ± 112 per 10 5 nuclei, n=6 for each, P =0.03). Quantitative RT-PCR showed that angiotensin II type 1a receptor and interleukin-6 were upregulated in viable LV samples from CRP-Tg mice compared with controls. Increased CRP expression exacerbates LV dysfunction and remodeling after MI, associated with increased apoptotic rates, increased angiotensin II receptor expression and exaggerated inflammatory response.
Extrapulmonary tuberculosis in the European Union and European Economic Area, 2002 to 2011
Authors: A Sandgren, V Hollo, M J van der Werf
Journal: Eurosurveillance (2013)

Tuberculosis (TB) is decreasing in the European Union/European Economic Area (EU/EEA), but remains a significant public health problem. Although pulmonary TB accounts for the majority of the cases and is the main transmissible form of the disease, extrapulmonary TB also contributes to the burden of disease and does not receive specific attention in international control strategies. We performed a descriptive analysis to assess the burden and trends of extrapulmonary TB in EU/EEA countries. During 2002–11, 167,652 cases of extrapulmonary TB were reported by the 30 Member States. Extrapulmonary TB accounted for 19.3% of all notified cases, ranging from 5.8% to 44.4% among the Member States. Overall, TB notification rates decreased in 2002–11 due to a decrease in pulmonary TB. Notification rates of extrapulmonary TB remained stable at 3.4 per 100,000 in 2002 and 3.2 per 100,000 in 2011. Thus the proportion of extrapulmonary TB increased from 16.4% in 2002 to 22.4% in 2011. Of all extrapulmonary TB cases reported during 2002–11, 37.9% were foreign-born or citizens of another country, 33.7% were culture-confirmed, and the overall treatment success was 81.4%. A significant percentage of notified TB cases are extrapulmonary, and in contrast to pulmonary TB, extrapulmonary TB rates are not decreasing.
Chromosomes and Serum Proteins
Authors: W. N. Rashad, W. R. M. Morton
Journal: BMJ (1964)

buzzer, seem only to work when the emotional problems in the child are secondary to the shame and embarrassment of the wetting itself.Psycho-dynamics is not a mysterious or necessarily foul piece of theorizing.Some- one, like myself, who is prepared to use physical or psycho-therapeutic methods, finds that where the wetting is used as part of the emotional disorder-for example, as an aggressive weapon against an over-controlling mother-physical methods of treatment almost always fail.Presumably the child sees these methods as only further assaults on it, this time by a doctor who is allying himself with the punitive parent.I make no apology for trying to be con- troversial in criticizing those who take a mechanistic view of psychiatry.One tires of the division of a difficult subject into "'goodies" and " baddies," by, on the one hand, the over-organic types of theoreticians and, on the other, the almost religiously psycho-dynamic school.Let us have accurate diagnosis.