tbuckley/cabot-search huggingface dataset:
Total and Regional Myocardial Blood Flow Measurements with 25µ, 15µ, 9µ, and Filtered 1-10µ Diameter Microspheres and Antipyrine in Dogs and Sheep
Authors: JOSEPH UTLEY, EDWIN L. CARLSON, JULIEN I. E. HOFFMAN, HUGO M. MARTINEZ, GERALD D. BUCKBERG
Journal: Circulation Research (1974)

The accuracy of regional myocardial blood flow measurements made with microspheres of different sizes is uncertain. Therefore, we simultaneously injected radioactive microspheres of different sizes into the left atria of dogs and sheep; the microsphere diameters were 25µ, 15µ, 9µ, 1-l0µ, and filtered 1-10µ (most &gt; 7µ). Antipyrine was sometimes simultaneously infused for 15-60 seconds. Myocardial blood flow was altered by hemorrhage, tachycardia, supravalvar aortic constriction, or infusion of methoxamine or adenosine triphosphate; left coronary artery branches were occluded on two occasions. Sometimes the percent of untrapped microspheres was estimated. All sizes of microspheres measured similar total myocardial blood flows when the percent of untrapped microspheres was known. All indicators were distributed identically to the right and left ventricular free walls and septum; ischemic areas had a 1% excess of antipyrine. With any pair of microspheres, the larger had a subendocardial excess except for 25µ microspheres, which were in excess compared with 15µ microspheres in the higher flow layer whether it was subendocardial or subepicardial. The greatest difference for any pair of microspheres was 10.53% of flow in a layer. Antipyrine did not define which size of microspheres measured true regional blood flow, since many previously unemphasized limitations were discovered. Nevertheless, we believe that microspheres 9µ in diameter are probably the best for measuring regional myocardial blood flow.
International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family
Authors: Richard D. Ye, François Boulay, Ji Ming Wang, Claes Dahlgren, Craig Gerard, Marc Parmentier, Charles N. Serhan, Philip M. Murphy
Journal: Pharmacological Reviews (2009)

Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including <i>N</i>-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. <i>N</i>-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with <i>N</i>-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions.
Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival
Authors: Pattana Wangaryattawanich, Masumeh Hatami, Jixin Wang, Ginu Thomas, Adam Flanders, Justin Kirby, Max Wintermark, Erich S. Huang, Ali Shojaee Bakhtiari, Markus M. Luedi, Syed S. Hashmi, Daniel L. Rubin, James Y. Chen, Scott N. Hwang, John Freymann, Chad A. Holder, Pascal O. Zinn, Rivka R. Colen
Journal: Neuro-Oncology (2015)

Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM. We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image. Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm3 and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively). Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.
Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis
Authors: Z. Morris, W. N Whiteley, W T Longstreth, F. Weber, Y.-C. Lee, Y. Tsushima, H. Alphs, S. C Ladd, C. Warlow, J. M Wardlaw, R. Al-Shahi Salman
Journal: BMJ (2009)

<b>Objective</b> To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain. <b>Design</b> Systematic review and meta-analysis of observational studies. <b>Data sources</b> Ovid Medline (1950 to May 2008), Embase (1980 to May 2008), and bibliographies of relevant articles. <b>Review methods</b> Two reviewers sought and assessed studies of people without neurological symptoms who underwent MRI of the brain with or without intravenous contrast for research purposes or for occupational, clinical, or commercial screening. <b>Main outcome measures</b> Overall disease specific and age specific prevalence of incidental brain findings, calculated by meta-analysis of pooled proportions using DerSimonian-Laird weights in a random effects model. <b>Results</b> In 16 studies, 135 of 19 559 people had neoplastic incidental brain findings (prevalence 0.70%, 95% confidence interval 0.47% to 0.98%), and prevalence increased with age (χ<sup>2</sup> for linear trend, P=0.003). In 15 studies, 375 of 15 559 people had non-neoplastic incidental brain findings (prevalence 2.0%, 1.1% to 3.1%, excluding white matter hyperintensities, silent infarcts, and microbleeds). The number of asymptomatic people needed to scan to detect any incidental brain finding was 37. The prevalence of incidental brain findings was higher in studies using high resolution MRI sequences than in those using standard resolution sequences (4.3% <i>v</i> 1.7%, P&lt;0.001). The prevalence of neoplastic incidental brain findings increased with age. <b>Conclusions</b> Incidental findings on brain MRI are common, prevalence increases with age, and detection is more likely using high resolution MRI sequences than standard resolution sequences. These findings deserve to be mentioned when obtaining informed consent for brain MRI in research and clinical practice but are not sufficient to justify screening healthy asymptomatic people.
Low-Density Lipoprotein Upregulates Low-Density Lipoprotein Receptor-Related Protein Expression in Vascular Smooth Muscle Cells
Authors: Vicenta Llorente-Cortés, Marta Otero-Viñas, Sonia Sánchez, Cristina Rodríguez, Lina Badimon
Journal: Circulation (2002)

Background— Low-density lipoprotein (LDL) receptor-related protein (LRP) is highly expressed in vascular smooth muscle cells (VSMCs) of both normal and atherosclerotic lesions. However, little is known about LRP regulation in the vascular wall. Methods and Results— We analyzed the regulation of LRP expression in vitro in human VSMCs cultured with native LDL (nLDL) or aggregated LDL (agLDL) by semiquantitative reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, and Western blot and in vivo during diet-induced hypercholesterolemia by in situ hybridization. LRP expression in human VSMCs is increased by nLDL and agLDL in a time- and dose-dependent manner. Maximal induction of LRP mRNA expression was observed after 24 hours of exposure to LDL. However, agLDL induced higher LRP mRNA expression (3.0-fold) than nLDL (1.76-fold). LRP mRNA upregulation was associated with an increase on LRP protein expression with the greatest induction by agLDL. VSMC-LRP upregulation induced by nLDL or agLDL was reduced by an inhibitor of sterol regulatory element binding protein (SREBP) catabolism ( N -acetyl-leucyl-leucyl-norleucinal). In situ hybridization analysis indicates that there is a higher VSMC-LRP expression in hypercholesterolemic than in normocholesterolemic pig aortas. Conclusions— These results indicate that LRP expression in VSMCs is upregulated by intravascular and systemic LDL.
Pulmonary vasodilator responses to vagal stimulation and acetylcholine in the cat.
Authors: P A Nandiwada, A L Hyman, P J Kadowitz
Journal: Circulation Research (1983)

Responses to vagal stimulation and acetylcholine were investigated in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow and constant left atrial pressure. Under baseline conditions, electrical stimulation of vagal efferent fibers increases lobar arterial pressure. However, when vasoconstrictor tone was increased, a depressor response was unmasked. The pressor response under baseline conditions and the depressor response under enhanced tone conditions were blocked by phenoxybenzamine and atropine. These data suggest that, in the cat, the vagus is composed of efferent fibers from both the sympathetic and parasympathetic systems. After treatment with 6-hydroxydopamine to destroy the integrity of the sympathetic system, vagal stimulation caused significant frequency-dependent decreases in lobar arterial pressure when lobar vascular tone was increased by infusion of a stable prostaglandin endoperoxide analog or ventilatory hypoxia. Injections of acetylcholine also caused significant dose-related decreases in lobar arterial pressure when lobar vascular resistance was elevated. Depressor responses to vagal stimulation and acetylcholine in 6-hydroxydopamine-treated animals were blocked by atropine and enhanced by physostigmine. Decreases in lobar arterial pressure in response to vagal stimulation in 6-hydroxydopamine-treated animals with enhanced tone were blocked by hexamethonium, whereas responses to injected acetylcholine were not altered by the ganglionic blocking agent. Decreases in lobar arterial pressure in response to vagal stimulation and acetylcholine were similar when the lung was ventilated and when the left lower lobe bronchus was obstructed. In addition, responses to vagal stimulation were similar when systemic arterial pressure was decreased to the level of pressure in the perfused lobar artery. Responses to acetylcholine were not altered after treatment with 5,8,11,14-eicosatetraynoic acid, a lipoxygenase inhibitor. The present data suggest that the feline pulmonary vascular bed is functionally innervated by cholinergic nerves and that vagal stimulation dilates the pulmonary vascular bed by releasing acetylcholine which acts on muscarinic receptors in pulmonary vessels.
Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury
Authors: Pinelopi P. Kapitsinou, Hideto Sano, Mark Michael, Hanako Kobayashi, Olena Davidoff, Aihua Bian, Bing Yao, Ming-Zhi Zhang, Raymond C. Harris, Kevin J. Duffy, Connie L. Erickson-Miller, Timothy A. Sutton, Volker H. Haase
Journal: Journal of Clinical Investigation (2014)

The hypoxia-inducible transcription factors HIF-1 and HIF-2 mediate key cellular adaptions to hypoxia and contribute to renal homeostasis and pathophysiology; however, little is known about the cell type-specific functions of HIF-1 and HIF-2 in response to ischemic kidney injury. Here, we used a genetic approach to specifically dissect the roles of endothelial HIF-1 and HIF-2 in murine models of hypoxic kidney injury induced by ischemia reperfusion or ureteral obstruction. In both models, inactivation of endothelial HIF increased injury-associated renal inflammation and fibrosis. Specifically, inactivation of endothelial HIF-2α, but not endothelial HIF-1α, resulted in increased expression of renal injury markers and inflammatory cell infiltration in the postischemic kidney, which was reversed by blockade of vascular cell adhesion molecule-1 (VCAM1) and very late antigen-4 (VLA4) using monoclonal antibodies. In contrast, pharmacologic or genetic activation of HIF via HIF prolyl-hydroxylase inhibition protected wild-type animals from ischemic kidney injury and inflammation; however, these same protective effects were not observed in HIF prolyl-hydroxylase inhibitor-treated animals lacking endothelial HIF-2. Taken together, our data indicate that endothelial HIF-2 protects from hypoxia-induced renal damage and represents a potential therapeutic target for renoprotection and prevention of fibrosis following acute ischemic injury.
Primary Pulmonary Hypertension: Improved Long-Term Effects and Survival With Continuous Intravenous Epoprostenol Infusion
Authors: Shelley M Shapiro, Ronald J Oudiz, Tiesheng Cao, Matthew A Romano, X.Joy Beckmann, Demitrios Georgiou, Sarathy Mandayam, Leonard E Ginzton, Bruce H Brundage
Journal: Journal of the American College of Cardiology (1997)
Primary CNS <i>CCND1</i>/<i>MYC</i>-Positive Double-Hit B-Cell Lymphoma: A Case Report and Review of the Literature
Authors: Hiroko Sakurai, Kei-Ji Sugimoto, Asami Shimada, Hidenori Imai, Mutsumi Wakabayashi, Yasunobu Sekiguchi, Yasunori Ota, Koji Izutsu, Kengo Takeuchi, Norio Komatsu, Masaaki Noguchi
Journal: Journal of Clinical Oncology (2014)
Pulmonary arterial remodeling induced by a Th2 immune response
Authors: Eleen Daley, Claire Emson, Christophe Guignabert, Rene de Waal Malefyt, Jennifer Louten, Viswanath P. Kurup, Cory Hogaboam, Laimute Taraseviciene-Stewart, Norbert F. Voelkel, Marlene Rabinovitch, Ekkehard Grunig, Gabriele Grunig
Journal: The Journal of Experimental Medicine (2008)

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH.
Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG)
Authors: J. Aparicio, P. Maroto, X. García del Muro, A. Sánchez-Muñoz, J. Gumà, M. Margelí, A. Sáenz, N. Sagastibelza, D. Castellano, J.A. Arranz, D. Hervás, R. Bastús, A. Fernández-Aramburo, J. Sastre, J. Terrasa, M. López-Brea, J. Dorca, D. Almenar, J. Carles, A. Hernández, J.R. Germà
Journal: Annals of Oncology (2014)
Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial
Authors: G Roberts
Journal: Thorax (2003)

<b>Background:</b> The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study. <b>Methods:</b> Children aged 1–16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids. Subjects were randomised to receive either a short intravenous bolus of salbutamol (15 μg/kg over 20 minutes) followed by a saline infusion or an aminophylline infusion (5 mg/kg over 20 minutes) followed by 0.9 mg/kg/h. <b>Results:</b> Forty four subjects were enrolled, with 18 randomly allocated to receive salbutamol and 26 to receive aminophylline. The groups were well matched at baseline. An intention to treat analysis showed that there was no statistically significant difference in the asthma severity score (ASS) at 2 hours between the two groups (median (IQR) 6 (6, 8) and 6.5 (5, 8) for salbutamol and aminophylline respectively, p=0.93). A similar improvement in ASS to 2 hours was seen in the two groups (mean difference –0.08, 95% CI –0.97 to 0.80), there was a trend (p=0.07) towards a longer duration of oxygen therapy in the salbutamol group (17.8 hours (95% CI 8.5 to 37.5) <i>v</i> 7.0 hours (95% CI 3.4 to 14.2)), and a significantly (p=0.02) longer length of hospital stay in the salbutamol group (85.4 (95% CI 66.1 to 110.2) hours <i>v</i> 57.3 hours (95% CI 45.6 to 72.0)). There was no significant difference in adverse events between the two groups. <b>Conclusions:</b> This study suggests that, in severe childhood asthma, there is no significant difference in the effectiveness of a bolus of salbutamol and an aminophylline infusion in the first 2 hours of treatment. Overall, the aminophylline infusion was superior as it significantly reduced the length of stay in hospital.
Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma
Authors: S. Yin, A. Girnita, T. Stromberg, Z. Khan, S. Andersson, H. Zheng, C. Ericsson, M. Axelson, M. Nister, O. Larsson, T. J. Ekstrom, L. Girnita
Journal: Neuro-Oncology (2009)

Glioblastoma (GB) is the most common malignant brain tumor in adults. It has limited treatment opportunities and is almost exclusively fatal. Owing to the central role the insulin-like growth factor-1 receptor (IGF-1R) plays in malignant cells, it has been suggested as a target for anticancer therapy including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without affecting the highly homologous insulin receptor. Here, we show that PPP inhibits growth of human GB cell lines along with reduced phosphorylation of IGF-1R and AKT. In vivo, PPP-treatment causes dramatic tumor regression not only in subcutaneous xenografts but also in intracerebral xenografts, indicating passage of PPP across the blood-brain barrier.
Calcium kinetics in individual heart segments
Authors: J. T SAARI, J. A JOHNSON
Journal: Cardiovascular Research (1980)

Journal Article Calcium kinetics in individual heart segments Get access JACK T SAARI, JACK T SAARI ** From the Department of Physiology, University of North Dakota, Grand Forks, North Dakota† From the Department of Physiology, University of Minnesota, Minneapolis, Minnesota Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN A JOHNSON JOHN A JOHNSON † From the Department of Physiology, University of Minnesota, Minneapolis, Minnesota Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 14, Issue 12, December 1980, Pages 731–734, https://doi.org/10.1093/cvr/14.12.731 Published: 01 December 1980
Stress effects on gastrointestinal transit in the rat.
Authors: P Enck, V Merlin, J F Erckenbrecht, M Wienbeck
Journal: Gut (1989)

Previous investigations of stress effects on gastric emptying, orocaecal, and colonic transit in rats have produced conflicting results. Here one type of stressor, a 9passive avoidance9 situation, was used to investigate its effects on gastric emptying, orocaecal and colonic transit. After the rats had been trained to eat a standard amount of semisolid food, gastric emptying was determined (n = 12) by the food remaining in the stomach after various periods of rest, or stress exposure. Orocaecal transit (n = 14) was determined by breath hydrogen measurements after the food had been labelled with 1 g lactose. Colonic transit (n = 18) was measured as the arrival time of coloured faeces after infusion of a carmine red solution into the caecum through a chronically implanted catheter. The stressor had differential effects on transit through the stomach, small bowel and colon: gastric emptying was delayed (p less than 0.05) after stress (t1/2 = 2.66 h after stress, 1.97 h at rest). Orocaecal transit was accelerated (p less than 0.05) after stress; transit time decreased from 124.3 min at rest to 86.2 min after stress. Colonic transit was accelerated (p less than 0.01) under stress, from 15.5 h to 1.29 h. It is concluded that gastrointestinal transit in different parts of the gastrointestinal tract is differently affected by central nervous stimuli.