tbuckley/cabot-search huggingface dataset:
Blood Pressure in Children with Obstructive Sleep Apnea
Authors: CAROLE L. MARCUS, MARY G. GREENE, JOHN L. CARROLL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Hypertension is a common complication of obstructive sleep apnea in adults. However, hypertension has not been studied systematically in children with the obstructive sleep apnea syndrome (OSAS). We therefore measured blood pressure (BP) during polysomnography in 41 children with OSAS, compared to 26 children with primary snoring (PS). Systolic and diastolic BP were measured every 15 min via an appropriately sized arm cuff, using an automated system. This was tolerated by the children without inducing arousals from sleep. Children with OSAS had a significantly higher diastolic BP than those with PS (p < 0.001 for sleep and p < 0.005 for wakefulness). There was no significant difference in systolic BP between the two groups. Multiple linear regression showed that blood pressure could be predicted by apnea index, body mass index, and age. Blood pressure during sleep was lower than during wakefulness (p < 0.001 for diastole and p < 0.01 for systole), but did not differ significantly between rapid eye movement (REM) and non–REM sleep. We conclude that childhood OSAS is associated with systemic diastolic hypertension.
NF-κB induces miR-148a to sustain TGF-β/Smad signaling activation in glioblastoma
Authors: Hui Wang, Jian-Qing Pan, Lun Luo, Xin-jie Ning, Zhuo-Peng Ye, Zhe Yu, Wen-Sheng Li
Journal: Molecular Cancer (2015)

Inflammatory cytokines and transforming growth factor-β (TGF-β) are mutually inhibitory. However, hyperactivation of nuclear factor-κB (NF-κB) and TGF-β signaling both emerge in glioblastoma. Here, we report microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a directly suppressed Quaking (QKI), a negative regulator of TGF-β signaling. We determined NF-κB and TGF-β/Smad signaling activity using pNF-κB-luc, pSMAD-luc, and control plasmids. The association between an RNA-induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase kinase–associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real-time PCR. Xenograft tumors were established in the brains of nude mice. QKI suppression induced an aggressive phenotype of glioblastoma cells both in vitro and in vivo. Interestingly, we found that NF-κB induced miR-148a expression, leading to enhanced-strength and prolonged-duration TGF-β/Smad signaling. Notably, these findings were consistent with the significant correlation between miR-148a levels with NF-κB hyperactivation and activated TGF-β/Smad signaling in a cohort of human glioblastoma specimens. These findings uncover a plausible mechanism for NF-κB–sustained TGF-β/Smad activation via miR-148a in glioblastoma, and may suggest a new target for clinical intervention in human cancer.
Anti-DNA antibodies bind to DNase I.
Authors: A Puccetti, M P Madaio, G Bellese, P Migliorini
Journal: The Journal of Experimental Medicine (1995)

Polyspecificity is a well-known property of the anti-DNA antibodies produced by autoimmune animals. In our search for antigen targets of anti-DNA antibodies within tissue extracts, we identified a 32-kD polypeptide that was recognized by a large panel of anti-DNA antibodies. Direct sequencing of this protein disclosed its identity with DNase I. 22 monoclonal anti-DNA antibodies bound to DNase I in direct and competitive immunoassays; out of 15 autoantibodies that did not bind DNA, none had the ability to bind DNase I. The ability of anti-DNA antibodies to interfere with DNase I enzymatic activity was evaluated in an assay based on the enzyme digestion of phage double strand DNA. Six monoclonal anti-single strand DNA antibodies that did not bind double strand DNA were tested in this assay. Three out of six inhibited DNase I-mediated digestion of phage DNA. The interaction of anti-DNA antibodies with DNase I was further investigated by testing their ability to bind a synthetic peptide that corresponds to the catalytic site of the molecule. 4 out of 22 anti-DNA antibodies bound the active site peptide; two of these had been shown to inhibit DNase I enzymatic activity. This report show that anti-DNA antibodies recognize both DNA and its natural ligand DNase I. Some anti-DNA antibodies inhibit DNase I enzymatic activity, thus displaying the potential to modulate DNA catabolism. The dual specificity of anti-DNA antibodies offers a clue for understanding the mechanisms that lead to anti-DNA antibody production in autoimmune animals.
2012 ACCF/AATS/SCAI/STS Expert Consensus Document on Transcatheter Aortic Valve Replacement
Authors: David R. Holmes, Michael J. Mack, Sanjay Kaul, Arvind Agnihotri, Karen P. Alexander, Steven R. Bailey, John H. Calhoon, Blase A. Carabello, Milind Y. Desai, Fred H. Edwards, Gary S. Francis, Timothy J. Gardner, A. Pieter Kappetein, Jane A. Linderbaum, Chirojit Mukherjee, Debabrata Mukherjee, Catherine M. Otto, Carlos E. Ruiz, Ralph L. Sacco, Donnette Smith, James D. Thomas
Journal: Journal of the American College of Cardiology (2012)
Resorufin analogs preferentially bind cerebrovascular amyloid: potential use as imaging ligands for cerebral amyloid angiopathy
Authors: Byung Han, Meng-liang Zhou, Ananth K Vellimana, Eric Milner, David H Kim, Jacob K Greenberg, Wenhua Chu, Robert H Mach, Gregory J Zipfel
Journal: Molecular Neurodegeneration (2011)

Cerebral amyloid angiopathy (CAA) is characterized by deposition of fibrillar amyloid β (Aβ) within cerebral vessels. It is commonly seen in the elderly and almost universally present in patients with Alzheimer's Disease (AD). In both patient populations, CAA is an independent risk factor for lobar hemorrhage, ischemic stroke, and dementia. To date, definitive diagnosis of CAA requires obtaining pathological tissues via brain biopsy (which is rarely clinically indicated) or at autopsy. Though amyloid tracers labeled with positron-emitting radioligands such as [11C]PIB have shown promise for non-invasive amyloid imaging in AD patients, to date they have been unable to clarify whether the observed amyloid load represents neuritic plaques versus CAA due in large part to the low resolution of PET imaging and the almost equal affinity of these tracers for both vascular and parenchymal amyloid. Therefore, the development of a precise and specific non-invasive technique for diagnosing CAA in live patients is desired.We found that the phenoxazine derivative resorufin preferentially bound cerebrovascular amyloid deposits over neuritic plaques in the aged Tg2576 transgenic mouse model of AD/CAA, whereas the congophilic amyloid dye methoxy-X34 bound both cerebrovascular amyloid deposits and neuritic plaques. Similarly, resorufin-positive staining was predominantly noted in fibrillar Aβ-laden vessels in postmortem AD brain tissues. Fluorescent labeling and multi-photon microscopy further revealed that both resorufin- and methoxy-X34-positive staining is colocalized to the vascular smooth muscle (VSMC) layer of vessel segments that have severe disruption of VSMC arrangement, a characteristic feature of CAA. Resorufin also selectively visualized vascular amyloid deposits in live Tg2576 mice when administered topically, though not systemically. Resorufin derivatives with chemical modification at the 7-OH position of resorufin also displayed a marked preferential binding affinity for CAA, but with enhanced lipid solubility that indicates their use as a non-invasive imaging tracer for CAA is feasible.To our knowledge, resorufin analogs are the fist class of amyloid dye that can discriminate between cerebrovascular and neuritic forms of amyloid. This unique binding selectivity suggests that this class of dye has great potential as a CAA-specific amyloid tracer that will permit non-invasive detection and quantification of CAA in live patients.
Mature Cytotoxic CD56bright/CD16<i>+</i>Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma
Authors: Meriem Messaoudene, Giulia Fregni, Emmanuelle Fourmentraux-Neves, Johan Chanal, Eve Maubec, Sarra Mazouz-Dorval, Benoit Couturaud, Angelique Girod, Xavier Sastre-Garau, Sebastien Albert, Charles Guédon, Lydia Deschamps, Delphine Mitilian, Isabelle Cremer, Nicolas Jacquelot, Sylvie Rusakiewicz, Laurence Zitvogel, Marie-Francoise Avril, Anne Caignard
Journal: Cancer Research (2013)

Abstract Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56bright NK cells among CD45+ hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56brightCD16+ NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN–derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node–positive melanoma. Cancer Res; 74(1); 81–92. ©2013 AACR.
Identification of patients with gout: elaboration of a questionnaire for epidemiological studies
Authors: P Richette, P Clerson, S Bouée, G Chalès, M Doherty, R M Flipo, C Lambert, F Lioté, T Poiraud, T Schaeverbeke, T Bardin
Journal: Annals of the Rheumatic Diseases (2014)

<b>Objective:</b> To examine whether physical activity is independently associated with direct health care costs in community-dwelling older adults with multiple chronic conditions. <b>Design:</b> Cross-sectional analysis. <b>Setting:</b> Research laboratory. <b>Participants:</b> Two hundred and nine community-dwelling men and women volunteers aged 65 years and older with chronic conditions. <b>Intervention:</b> None. <b>Main Outcome Measures:</b> Primary dependent variable was direct health care costs incurred in the previous three months. Participants completed the Health Resource Utilization (HRU) questionnaire. To estimate HRU, direct costs in the previous three months were calculated using the third party payer perspective of the British Columbia Ministry of Health, deemed representative of the Canadian health care system costs. For medications, we used the Retail Pharmacy Dispensed prescription cost tables. Primary independent variables were: 1) self-report current level of physical activity as assessed by the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD); and 2) general balance and mobility as assessed by the National Institute on Aging Balance Scale. <b>Results: </b>The mean number of chronic conditions per participant was six. Current level of physical activity was independently and inversely associated with HRU. Age, gender, number of chronic conditions, global cognitive function, body mass index, and general balance and mobility together accounted for 24.3% of the total variance. Adding PASIPD score resulted in an R-square change of 3.3% and significantly improved the model. The total variance accounted by the final model was 27.6%. <b>Conclusions:</b> Physical activity promotion may reduce health care costs in older adults with chronic conditions.
Phosphorylation of Smooth Muscle 22α Facilitates Angiotensin II–Induced ROS Production Via Activation of the PKCδ-P47 <sup>phox</sup> Axis Through Release of PKCδ and Actin Dynamics and Is Associated With Hypertrophy and Hyperplasia of Vascular Smooth Muscle Cells In Vitro and In Vivo
Authors: Pin Lv, Sui-Bing Miao, Ya-Nan Shu, Li-Hua Dong, George Liu, Xiao-Li Xie, Min Gao, Yu-Can Wang, Ya-Juan Yin, Xiao-Juan Wang, Mei Han
Journal: Circulation Research (2012)

Rationale: We have demonstrated that smooth muscle (SM) 22α inhibits cell proliferation via blocking Ras-ERK1/2 signaling in vascular smooth muscle cells (VSMCs) and in injured arteries. The recent study indicates that SM22α disruption can independently promote arterial inflammation through activation of reactive oxygen species (ROS)-mediated NF-κB pathways. However, the mechanisms by which SM22α controls ROS production have not been characterized. Objective: To investigate how SM22α disruption promotes ROS production and to characterize the underlying mechanisms. Methods and Results: ROS level was measured by dihydroethidium staining for superoxide and TBA assay for malondialdehyde, respectively. We showed that downregulation and phosphorylation of SM22α were associated with angiotensin (Ang) II–induced increase in ROS production in VSMCs of rats and human. Ang II induced the phosphorylation of SM22α at Serine 181 in an Ang II type 1 receptor–PKCδ pathway–dependent manner. Phosphorylated SM22α activated the protein kinase C (PKC)δ-p47 phox axis via 2 distinct pathways: (1) disassociation of PKCδ from SM22α, and in turn binding to p47 phox , in the early stage of Ang II stimulation; and (2) acceleration of SM22α degradation through ubiquitin-proteasome, enhancing PKCδ membrane translocation via induction of actin cytoskeletal dynamics in later oxidative stress. Inhibition of SM22α phosphorylation abolished the Ang II–activated PKCδ-p47 phox axis and inhibited the hypertrophy and hyperplasia of VSMCs in vitro and in vivo, accompanied with reduction of ROS generation. Conclusions: These findings indicate that the disruption of SM22α plays pivotal roles in vascular oxidative stress. PKCδ-mediated SM22α phosphorylation is a novel link between actin cytoskeletal remodeling and oxidative stress and may be a potential target for the development of new therapeutics for cardiovascular diseases.
A comparative study of refatting kinetics on the scalp and forehead
Authors: D. SAINT-LEGER, J. L. LEVEQUE
Journal: British Journal of Dermatology (1982)

A modified photometric technique has shown considerable differences between the refatting kinetics of the scalp and forehead. The refatting on the forehead occurs rapidly, probably due to the large follicular reservoir. The follicular reservoir of the scalp, which bears a large terminal hair, is much smaller and so the refatting time is longer. Thus, sebum excretion and sebum production rates probably correlate better on the scalp than on the forehead, and we suggest that the scalp may be a better site than the forehead for investigating sebaceous gland physiology.
MicroRNA Biogenesis and Cancer
Authors: Richard I. Gregory, Ramin Shiekhattar
Journal: Cancer Research (2005)

Abstract MicroRNAs (miRNA) are a recently discovered family of short non–protein-coding RNAs that negatively regulate gene expression. Recent studies of miRNAs highlight a requirement for cell viability. Posttranscriptional silencing of target genes by miRNAs occurs either by targeting specific cleavage of homologous mRNAs, or by targeting specific inhibition of protein synthesis. We recently identified a multisubunit protein complex termed Microprocessor that is necessary and sufficient for processing miRNA precursor RNAs. Microprocessor contains Drosha, an RNase III endonuclease, and DGCR8, a gene deleted in DiGeorge syndrome. We consider recent findings that link miRNA perturbation to cancer.
Imatinib (STI571)-Mediated Changes in Glucose Metabolism in Human Leukemia BCR-ABL-Positive Cells
Authors: Sven Gottschalk, Nora Anderson, Carsten Hainz, S. Gail Eckhardt, Natalie J. Serkova
Journal: Clinical Cancer Research (2004)

The therapeutic efficacy of imatinib mesylate (Gleevec) is based on its specific inhibition of the BCR-ABL oncogene protein, a widely expressed tyrosine kinase in chronic myelogenous leukemia (CML) cells. The goal of this study was to evaluate glucose metabolism in BCR-ABL-positive cells that are sensitive to imatinib exposure. Two human BCR-ABL-positive cell lines (CML-T1 and K562) and one BCR-ABL-negative cell line (HC-1) were incubated with different imatinib concentrations for 96 hours. Magnetic resonance spectroscopy on cell acid extracts was performed to evaluate [1-13C]glucose metabolism, energy state, and changes in endogenous metabolites after incubation with imatinib. Imatinib induced a concentration-dependent inhibition of cell proliferation in CML-T1 (IC50, 0.69 +/- 0.06 micromol/L) and K562 cells (IC50, 0.47 +/- 0.04 micromol/L), but not in HC-1 cells. There were no metabolic changes in imatinib-treated HC-1 cells. In BCR-ABL-positive cells, the relevant therapeutic concentrations of imatinib (0.1-1.0 micromol/L) decreased glucose uptake from the media by suppressing glycolytic cell activity (C3-lactate at 0.25 mmol/L, 65% for K562 and 77% for CML-T1 versus control). Additionally, the activity of the mitochondrial Krebs cycle was increased (C4-glutamate at 0.25 micromol/L, 147% for K562 and 170% for CML-T1). The improvement in mitochondrial glucose metabolism resulted in an increased energy state (nucleoside triphosphate/nucleoside diphosphate at 0.25 micromol/L, 130% for K562 and 125% for CML-T1). Apoptosis was observed at higher concentrations. Unlike standard chemotherapeutics, imatinib, without cytocidal activity, reverses the Warburg effect in BCR-ABL-positive cells by switching from glycolysis to mitochondrial glucose metabolism, resulting in decreased glucose uptake and higher energy state.
Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells.
Authors: K B Leung, K C Flint, J Brostoff, B N Hudspith, N M Johnson, H Y Lau, W L Liu, F L Pearce
Journal: Thorax (1988)

Sodium cromoglycate and nedocromil sodium produced a dose dependent inhibition of histamine secretion from human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymatic dissociation of lung parenchyma. Both compounds were significantly more active against the lavage cells than against the dispersed lung cells, and nedocromil sodium was an order of magnitude more effective than sodium cromoglycate against both cell types. Tachyphylaxis was observed with the parenchymal cells but not with the lavage cells. Nedocromil sodium and sodium cromoglycate also inhibited histamine release from the lavage cells of patients with sarcoidosis and extrinsic asthma.
Evidence Tips the Scale Toward Screening for Hyperglycemia
Authors: K.M. Venkat Narayan, Unjali P. Gujral
Journal: Diabetes Care (2015)

Screening and early detection for hyperglycemia is a topic of considerable interest, and there is debate as to its overall benefits (1). Policies for screening vary from the position of the American Diabetes Association (2), which recommends glucose testing in all people aged 45 years and over or at high risk for type 2 diabetes, to the position of the U.S. Preventive Services Task Force (USPSTF), which recommends only testing those with sustained hypertension (3). The USPSTF, however, is deliberating its new draft recommendations, which broaden the criteria for type 2 diabetes and prediabetes screening (http://www.uspreventiveservicestaskforce.org/Page/Document/draft-research-plan49/screening-for-abnormal-glucose-and-type-2-diabetes-mellitus). As screening and early detection for hyperglycemia remains a topic of great interest, the article from Herman et al. (4) in this issue of Diabetes Care is timely. Specifically, Herman et al. (4) report on the beneficial effect of type 2 diabetes screening on cardiovascular (CVD) morbidity and mortality in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) trial.

Diabetes is a global problem, affecting 387 million people worldwide (5), that is growing in all countries, in urban and rural areas and projected to affect approximately 600 million individuals by 2035 (5). Type 2 diabetes (accounting for about 95% of all diabetes cases) often exists asymptomatically (6), and approximately 50% of cases globally (varying from 30% to 80% across countries) remain undiagnosed (1). Eighty percent of people with diabetes live in developing countries, and the majority of those affected are aged 40–59 years (5). In addition …
Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa
Authors: Peter McErlean, Sergejs Berdnikovs, Silvio Favoreto, Junqing Shen, Assel Biyasheva, Rebecca Barbeau, Chris Eisley, Andrea Barczak, Theresa Ward, Robert P Schleimer, David J Erle, Homer A Boushey, Pedro C Avila
Journal: Genome Medicine (2014)

Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.