tbuckley/cabot-search huggingface dataset:
CEBPA-regulated lncRNAs, new players in the study of acute myeloid leukemia
Authors: James M Hughes, Beatrice Salvatori, Federico M Giorgi, Irene Bozzoni, Alessandro Fatica
Journal: Journal of Hematology & Oncology (2014)

CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation. Disruption of CEBPA function contributes to the development of acute myeloid leukemia (AML). CEBPA regulates a large number of protein coding genes of which several were shown to contribute to CEBPA function. In this study, we expand the analysis of CEBPA transcriptional targets to the newly identified class of long non-coding RNAs. We show that lncRNAs are a main component of the transcriptional program driven by C/EBPα and that many of these are also induced during granulocytic differentiation of AML cell lines supporting their relevance in proliferation arrest and differentiation.
Effects of Exercise on Treatment-Related Adverse Effects for Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Systematic Review
Authors: Jason R. Gardner, Patricia M. Livingston, Steve F. Fraser
Journal: Journal of Clinical Oncology (2013)

Androgen-deprivation therapy is a commonly used treatment for men with prostate cancer; however, the adverse effects can be detrimental to patient health and quality of life. Exercise has been proposed as a strategy for ameliorating a range of these treatment-related adverse effects. We conducted a systematic review of the literature regarding the effects of exercise on treatment-related adverse effects in men receiving androgen-deprivation therapy for prostate cancer.An online electronic search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, SPORTDiscus, and Health Source databases was performed to identify relevant peer-reviewed articles published between January 1980 and June 2013. Eligible study designs included randomized controlled trials as well as uncontrolled trials with pre- and postintervention data. Information was extracted regarding participant and exercise intervention characteristics as well as the effects of exercise on bone health, body composition, physical performance, cardiometabolic risk, fatigue, and quality of life.Ten studies were included, with exercise interventions involving aerobic and/or resistance training. Exercise training demonstrated benefits in muscular strength, cardiorespiratory fitness, functional task performance, lean body mass, and fatigue, with inconsistent effects observed for adiposity. The impact of exercise on bone health, cardiometabolic risk markers, and quality of life are currently unclear.Among patients with prostate cancer treated with androgen-deprivation therapy, appropriately prescribed exercise is safe and may ameliorate a range of treatment-induced adverse effects. Ongoing research of high methodologic quality is required to consolidate and expand on current knowledge and to allow the development of specific evidence-based exercise prescription recommendations.
The Ca <sub>V</sub> 3.2 T-Type Ca <sup>2+</sup> Channel Is Required for Pressure Overload–Induced Cardiac Hypertrophy in Mice
Authors: Chien-Sung Chiang, Ching-Hui Huang, Hockling Chieng, Ya-Ting Chang, Dory Chang, Ji-Jr Chen, Yong-Cyuan Chen, Yen-Hui Chen, Hee-Sup Shin, Kevin P. Campbell, Chien-Chang Chen
Journal: Circulation Research (2009)

Voltage-gated T-type Ca(2+) channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what the mechanism might be. Here we show that the alpha(1H) voltage-gated T-type Ca(2+) channel (Ca(v)3.2) is involved in the pathogenesis of cardiac hypertrophy via the activation of calcineurin/nuclear factor of activated T cells (NFAT) pathway. Specifically, pressure overload-induced hypertrophy was severely suppressed in mice deficient for Ca(v)3.2 (Ca(v)3.2(-/-)) but not in mice deficient for Ca(v)3.1 (Ca(v)3.1(-/-)). Angiotensin II-induced cardiac hypertrophy was also suppressed in Ca(v)3.2(-/-) mice. Consistent with these findings, cultured neonatal myocytes isolated from Ca(v)3.2(-/-) mice fail to respond hypertrophic stimulation by treatment with angiotensin II. Together, these results demonstrate the importance of Ca(v)3.2 in the development of cardiac hypertrophy both in vitro and in vivo. To test whether Ca(v)3.2 mediates the hypertrophic response through the calcineurin/NFAT pathway, we generated Ca(v)3.2(-/-), NFAT-luciferase reporter mice and showed that NFAT-luciferase reporter activity failed to increase after pressure overload in the Ca(v)3.2(-/-)/NFAT-Luc mice. Our results provide strong genetic evidence that Ca(v)3.2 indeed plays a pivotal role in the induction of calcineurin/NFAT hypertrophic signaling and is crucial for the activation of pathological cardiac hypertrophy.
Distribution of α-Galactosidase A in Normal Human Kidney and Renal Accumulation and Distribution of Recombinant α-Galactosidase A in Fabry Mice
Authors: Erik I. Christensen, Qun Zhou, Søren S. Sørensen, A[Combining Ring Above]se K. Rasmussen, Christian Jacobsen, Ulla Feldt-Rasmussen, Rikke Nielsen
Journal: Journal of the American Society of Nephrology (2007)

Deficiency of lysosomal α-galactosidase A (α-Gal A) in Fabry disease results in cellular accumulation of globotriaosylceramide (Gl3), often leading to end-stage renal failure. Gl3 accumulates in endothelial, glomerular, and tubular cells. Replacement therapy with recombinant α-Gal A to some extent reduces cellular accumulation of Gl3 in the kidney. This study shows high lysosomal expression of α-Gal A in all tubular segments and interstitial cells of normal human kidney. However, glomeruli and endothelial cells did not express the enzyme to any significant extent. Recombinant enzyme was taken up by rat yolk sac cells in a receptor-associated protein–inhibitive manner, and surface plasmon resonance experiments revealed binding to megalin, indicating a possible mechanism for uptake of α-Gal A in the tubular cells. After infusion into experimental animals or patients, α-Gal A was recovered in the urine, indicating glomerular filtration. Recombinant α-Gal A was also found in kidneys of normal and α-Gal A knockout mice by Western blotting and localized to endosomes and lysosomes in proximal tubules, interstitial cells, and glomerular podocytes by immunocytochemistry and autoradiography but not in vascular endothelial cells. In conclusion, intravenously administered enzyme is taken up by interstitial cells, is to some extent filtered in glomeruli, and is taken up by podocytes and reabsorbed by receptor-mediated endocytosis in proximal tubule cells, directly indicating a potential beneficial effect of enzyme replacement therapy for these cells.
The first reference equations for the 6-minute walk distance over a 10 m course: Table 1
Authors: Emmylou Beekman, Ilse Mesters, Rik Gosselink, Mariska P M Klaassen, Erik J M Hendriks, Onno C P Van Schayck, Rob A de Bie
Journal: Thorax (2014)

<h3>Rationale</h3> As primary care practice space is mostly limited to 10 m, the 6-minute walk test (6MWT) over a 10 m course is a frequently used alternative to evaluate patients’ performance in COPD. Considering that course length significantly affects distance walked in 6 minutes (6MWD), this study aims to develop appropriate reference equations for the 10 m 6MWT. <h3>Methods</h3> 181 healthy subjects, aged 40–90 years, performed two standardised 6MWTs over a straight 10 m course in a cross-sectional study. <h3>Results</h3> Average distance achieved was 578±108 m and differed between males and females (p&lt;0.001). Resulting sex-specific reference equations from multiple regression analysis included age, body mass index and change in heart rate, explaining 62% of the variance in 6MWD for males and 71% for females. <h3>Conclusions</h3> The presented reference equations are the first to evaluate 6MWD over a 10 m course and expand the usefulness of the 6MWT.
Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets
Authors: H.H. Nienhuis, S.B.M. Gaykema, H. Timmer-Bosscha, M. Jalving, A.H. Brouwers, M.N. Lub-de Hooge, B. van der Vegt, B. Overmoyer, E.G.E. de Vries, C.P. Schröder
Journal: Pharmacology & Therapeutics (2014)
Penicillium allergic alveolitis: faulty installation of central heating.
Authors: R J Fergusson, L J Milne, G K Crompton
Journal: Thorax (1984)

A married couple presented with an illness typical of allergic alveolitis. A careful search of their home revealed a leak in the central heating system with a heavy fungal growth on wet flooring and linoleum. Two species of Penicillium, P chrysogenum and P cyclopium, were isolated from floorboards, linoleum, and settle plates. Antibodies against both these fungi were demonstrated in the serum of both patients by an enzyme linked immunosorbent assay (ELISA). Allergic alveolitis caused by P chrysogenum and P cyclopium has not been described previously.
Transmission of Human Immunodeficiency Virus in a Dental Practice
Authors: C Ciesielski, D Marianos, C Y Ou, R Dumbaugh, J Witte, R Berkelman, B Gooch, G Myers, C C Luo, G Schochetman
Journal: Annals of Internal Medicine (1992)

To determine if patients of a dentist with the acquired immunodeficiency syndrome (AIDS) became infected with human immunodeficiency virus (HIV) during their dental care and, if so, to identify possible mechanisms of transmission.Retrospective epidemiologic follow-up of the dentist, his office practice, and his former patients.The practice of a dentist with AIDS in Florida.A dentist with AIDS, his health care providers and employees, and former patients of the dentist, including eight HIV-infected patients.Identification of risks for HIV transmission (if present), degree of genetic relatedness of the viruses, and identification of infection control and other office practices.Five of the eight HIV-infected patients had no confirmed exposures to HIV other than the dental practice and were infected with HIV strains that were closely related to those of the dentist. Each of the five had invasive dental procedures, done by the dentist after he was diagnosed with AIDS. Four of these five patients shared visit days (P greater than 0.2). Breaches in infection control and other dental office practices to explain these transmissions could not be identified.Although the specific incident that resulted in HIV transmission to these patients remains uncertain, the epidemiologic evidence supports direct dentist-to-patient transmission rather than a patient-to-patient route.
Closing Volume Influences the Postural Effect on Oxygenation in Unilateral Lung Disease
Authors: KANG-HYEON CHOE, YONG-TAE KIM, TAE-SUN SHIM, CHAE-MAN LIM, SANG-DO LEE, YOUNSUCK KOH, WOO-SUNG KIM, DONG-SOON KIM, JIN-SOOK RYU, WON-DONG KIM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In normal adults, both blood flow and ventilation are distributed preferentially to the dependent lung zones. In adults with unilateral lung disease, arterial oxygenation improves when they are positioned with their good lung down because of improved matching of ventilation and perfusion. When the closing volume is increased, dependent airways are closed during tidal breathing, so that reduced ventilation-perfusion ratio and hypoxia develops and ventilation is preferentially distributed to the upper lung zones. We undertook an observational study on the effects of lateral recumbency on arterial oxygenation in adult patients with unilateral lung disease and tested the hypothesis that oxygenation in lateral recumbency might be influenced by an increase in closing volume. Arterial blood gases were analyzed in the supine, right and left lateral decubitus positions and the aaPo 2 was calculated in 44 randomly selected patients 49.9 ± 18.7 yr of age with unilateral pneumonia (23 cases) or pulmonary tuberculosis (21 cases). In 26 patients, individual PaO2 with the normal lung in the dependent position was higher than that with the diseased lung; the opposite was true for 18 patients. The difference in PaO2 and aaPo 2 between the two positions was statistically significant in both groups. In 16 patients (10 men and six women 49.2 ± 18.2 yr of age), we measured closing volume and determined the fractional ventilation to each lung by 133Xe lung scan in the three positions. In these 16 patients, the difference in PaO2 between the normal and the diseased lung in the dependent position was related significantly to the difference in the fractional ventilation going to the normal lung between the dependent and the supine position (r = 0.642, p = 0.007). The latter was related significantly to the % predicted closing volume (CV/VC) (r = − 0.597, p = 0.015). This study has shown that closing volume, as well as posture, might be involved in determining oxygenation in lateral recumbency in patients with unilateral lung disease.
The Retinoid X Receptor-Selective Retinoid, LGD1069, Down-regulates Cyclooxygenase-2 Expression in Human Breast Cells through Transcription Factor Crosstalk: Implications for Molecular-Based Chemoprevention
Authors: Gu Kong, Hee-Tae Kim, Kendall Wu, David DeNardo, Susan G. Hilsenbeck, Xiao-Chun Xu, William W. Lamph, Reid Bissonnette, Andrew J. Dannenberg, Powel H. Brown
Journal: Cancer Research (2005)

Abstract Retinoids and their derivatives can suppress the development of cancer in animals and in humans. We and others have shown that retinoid X receptor (RXR)-selective retinoids or “rexinoids” suppress the development of breast cancer in several animal models with minimal toxicity. LGD1069 (Bexarotene) is a potent RXR-selective retinoid with reduced toxicity compared with naturally occurring retinoids. In this study, we investigated the expression of LGD1069-modulated biomarkers. We previously did cDNA array analysis of LGD1069-treated breast cells using Affymetrix microarrays. These studies identified many LGD1069-regulated genes, one of which was cyclooxygenase-2 (COX-2). Because COX-2 inhibitors have been shown to prevent cancer in other model systems, we investigated whether LGD1069 inhibits the expression of COX-2 in mammary tissue and in normal human mammary epithelial cells (HMEC). In mouse mammary tumor virus-erbB2 mice treated with LGD1069, there was a marked decrease of COX-2 expression in both normal and malignant mammary tissues. The effect of LGD1069 on COX-2 expression was also investigated in normal human breast cells. COX-2 expression was markedly reduced by treatment with LGD1069 at the RNA and protein level in normal HMECs; LGD1069 suppressed COX-2 promoter activity. We also showed that LGD1069 inhibited activator protein (AP-1)-dependent transcription in these breast cells, and that suppression of COX-2 expression was due to sequestration of CBP/p300. These results from in vivo and in vitro studies suggest that LGD1069, an RXR-selective retinoid, inhibits COX-2 expression by suppression of COX-2 transcription in part through transrepression of the AP-1 transcription factor. Thus, RXR-selective retinoids that inhibit AP-1 activity and suppress COX-2 expression may be particularly promising drugs for breast cancer prevention. Furthermore, such RXR-selective retinoids may be most useful in combination with antiestrogens for more effective prevention of breast cancer in women at high risk of this disease.
Direct Intracranial, fMRI, and Lesion Evidence for the Causal Role of Left Inferotemporal Cortex in Reading
Authors: Raphaël Gaillard, Lionel Naccache, Philippe Pinel, Stéphane Clémenceau, Emmanuelle Volle, Dominique Hasboun, Sophie Dupont, Michel Baulac, Stanislas Dehaene, Claude Adam, Laurent Cohen
Journal: Neuron (2006)
Virulent but not Avirulent <i>Mycobacterium tuberculosis</i> Can Evade the Growth Inhibitory Action of a T Helper 1–dependent, Nitric Oxide Synthase 2–independent Defense in Mice
Authors: Yu-Jin Jung, Ronald LaCourse, Lynn Ryan, Robert J. North
Journal: The Journal of Experimental Medicine (2002)

Control of infection with virulent Mycobacterium tuberculosis (Mtb) in mice is dependent on the generation of T helper (Th)1-mediated immunity that serves, via secretion of interferon (IFN)-gamma and other cytokines, to upregulate the antimycobacterial function of macrophages of which the synthesis of inducible nitric oxide synthase (NOS)2 is an essential event. As a means to understanding the basis of Mtb virulence, the ability of gene-deleted mice incapable of making NOS2 (NOS2(-/-)), gp91(Phox) subunit of the respiratory burst NADPH-oxidase complex (Phox(-/-)), or either enzyme (NOS2/Phox(-/-)), to control airborne infection with the avirulent R1Rv and H37Ra strains of Mtb was compared with their ability control infection with the virulent H37Rv strain. NOS2(-/-), Phox(-/-), and NOS2/Phox(-/-) mice showed no deficiency in ability to control infection with either strain of avirulent Mtb. By contrast, NOS2(-/-) mice, but not Phox(-/-) mice, were incapable of controlling H37Rv infection and died early from neutrophil-dominated lung pathology. Control of infection with avirulent, as well as virulent Mtb, depended on the synthesis of IFN-gamma, and was associated with a substantial increase in the synthesis in the lungs of mRNA for IFN-gamma and NOS2, and with production of NOS2 by macrophages at sites of infection. The results indicate that virulent, but not avirulent, Mtb can overcome the growth inhibitory action of a Th1-dependent, NOS2-independent mechanism of defense.
ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice
Authors: Boris L. Vaisman, Gilles Lambert, Marcelo Amar, Charles Joyce, Toshimitsu Ito, Robert D. Shamburek, William J. Cain, Jamila Fruchart-Najib, Edward D. Neufeld, Alan T. Remaley, H. Bryan Brewer, Silvia Santamarina-Fojo
Journal: Journal of Clinical Investigation (2001)

The discovery of the ABCA1 lipid transporter has generated interest in modulating human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression. To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and macrophage expression of hABCA1 enhanced macrophage cholesterol efflux to apoA-I; increased plasma cholesterol, cholesteryl esters (CEs), free cholesterol, phospholipids, HDL cholesterol, and apoA-I and apoB levels; and led to the accumulation of apoE-rich HDL1. ABCA1 transgene expression delayed 125I-apoA-I catabolism in both liver and kidney, leading to increased plasma apoA-I levels, but had no effect on apoB secretion after infusion of Triton WR1339. Although the plasma clearance of HDL-CE was not significantly altered in hABCA1-Tg mice, the net hepatic delivery of exogenous 3H-CEt-HDL, which is dependent on the HDL pool size, was increased 1.5-fold. In addition, the cholesterol and phospholipid concentrations in hABCA1-Tg bile were increased 1.8-fold. These studies show that steady-state overexpression of ABCA1 in vivo (a) raises plasma apoB levels without altering apoB secretion and (b) raises plasma HDL-C and apoA-I levels, facilitating hepatic reverse cholesterol transport and biliary cholesterol excretion. Similar metabolic changes may modify atherogenic risk in humans.
The Diagnostic Clue of "Hypercompetency"
Authors: MYRON H. MARSHALL, H. L. P. RESNIK
Journal: American Journal of Psychiatry (1968)

During an examination for competency to stand trial, the authors were impressed with a patient's "hypercompetency"—in this case, his extensive knowledge of the legal process. This observation, along with others, substantiated a diagnosis of paranoid personality. The authors give four criteria to assist in similar diagnostic situations.
Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease
Authors: Patrick Mallia, Joseph Footitt, Rosa Sotero, Annette Jepson, Marco Contoli, Maria-Belen Trujillo-Torralbo, Tatiana Kebadze, Julia Aniscenko, Gregory Oleszkiewicz, Katrina Gray, Simon D. Message, Kazuhiro Ito, Peter J. Barnes, Ian M. Adcock, Alberto Papi, Luminita A. Stanciu, Sarah L. Elkin, Onn M. Kon, Malcolm Johnson, Sebastian L. Johnston
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.Objectives: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations.Methods: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and β-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants.Measurements and Main Results: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5–9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load.Conclusions: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.
Osteopontin Plays an Important Role in the Development of Medial Thickening and Neointimal Formation
Authors: Kikuo Isoda, Kenichirou Nishikawa, Yashuhiro Kamezawa, Mikoto Yoshida, Masatoshi Kusuhara, Masao Moroi, Norihiro Tada, Fumitaka Ohsuzu
Journal: Circulation Research (2002)

Osteopontin (OPN) is a soluble secreted phosphoprotein that binds with high affinity to several integrins and it has been found at the site of atherosclerotic lesions. However, the role of OPN expression in vivo is still poorly understood. To investigate the physiological role of OPN in detail, we generated transgenic mice (Tg) overexpressing the OPN gene under control of the cytomegalovirus enhancer/chicken β-actin promoter. We detected OPN mRNAs in almost all tissues of 3 lines of Tg mice by Northern blotting. The serum levels of OPN were significantly higher in Tg than in non-Tg mice (782±107 versus 182±44 ng/mL; P &lt;0.001). Compared with non-Tg mice, a 73% (88±6 versus 51±7 μm; P &lt;0.001) and 94% (126±15 versus 73±11 μm; P &lt;0.0001) increase in the medial thickness of the aorta was determined in Tg mice at 16 and 32 weeks after birth. However, we found no evidence of inflammatory cells adhering to endothelial cells, intimal hyperplasia, or calcification in any region of Tg mice without artery injury. We then investigated the effect of cuff-induced injury to the femoral artery. The intimal thickening in Tg mice increased 2.9-fold more than that in non-Tg mice (4.9±1.9 versus 1.7±0.4 μm; P =0.022). The expression of OPN induces both medial thickening without injury and neointimal formation after injury, thus suggesting that OPN plays a role in the development of atherosclerosis, vascular remodeling, and restenosis after angioplasty in vivo.