tbuckley/cabot-search huggingface dataset:
Effect of ATP-Sensitive Potassium Channel Inhibition on Resting Coronary Vascular Responses in Humans
Authors: H. M. Omar Farouque, Stephen G. Worthley, Ian T. Meredith, R. Andrew P. Skyrme-Jones, Michael J. Zhang
Journal: Circulation Research (2002)

Experimental data suggest that vascular ATP-sensitive potassium (K ATP ) channels regulate coronary blood flow (CBF), but their role in regulating human CBF is unclear. We sought to determine the contribution of K ATP channels to resting conduit vessel and microvascular function in the human coronary circulation. Twenty-five patients (19 male/6 female, aged 56±12 years) were recruited. Systemic and coronary hemodynamics were assessed in 20 patients before and after K ATP channel inhibition with graded intracoronary glibenclamide infusions (4, 16, and 40 μg/min), in an angiographically smooth or mildly stenosed coronary artery following successful elective percutaneous coronary intervention to another vessel. Coronary blood velocity was measured with a Doppler guidewire and CBF calculated. Adenosine-induced hyperemia was determined following bolus intracoronary adenosine injection (24 μg). Time control studies were undertaken in 5 patients. Compared with vehicle infusion (0.9% saline), glibenclamide reduced resting conduit vessel diameter from 2.5±0.1 to 2.3±0.1 mm ( P &lt;0.01), resting CBF by 17% ( P =0.05), and resting CBF corrected for rate pressure-product by 18% ( P =0.01) in a dose-dependent manner. A corresponding 24% increase in coronary vascular resistance was noted at the highest dose ( P &lt;0.01). No alteration to resting CBF was noted in the time control studies. Glibenclamide reduced peak adenosine-induced hyperemia ( P =0.01) but did not alter coronary flow reserve. Plasma insulin increased from 5.6±1.2 to 7.6±1.3 mU/L ( P =0.02); however, plasma glucose was unchanged. Vascular K ATP channels are involved in the maintenance of basal coronary tone but may not be essential to adenosine-induced coronary hyperemia in humans.
Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts
Authors: Joshua Z Levin, Michael F Berger, Xian Adiconis, Peter Rogov, Alexandre Melnikov, Timothy Fennell, Chad Nusbaum, Levi A Garraway, Andreas Gnirke
Journal: Genome biology (2009)

Targeted RNA-Seq combines next-generation sequencing with capture of sequences from a relevant subset of a transcriptome. When testing by capturing sequences from a tumor cDNA library by hybridization to oligonucleotide probes specific for 467 cancer-related genes, this method showed high selectivity, improved mutation detection enabling discovery of novel chimeric transcripts, and provided RNA expression data. Thus, targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes.
Prevention and Treatment of Diabetic Nephropathy
Authors: Maura Ravera, Elena Ratto, Simone Vettoretti, Denise Parodi, Giacomo Deferrari
Journal: Journal of the American Society of Nephrology (2005)

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, with target BP &lt;130/80 mmHg being recommended. Angiotensin-converting enzyme inhibitors were found to be more effective than the other traditional agents in reducing the onset of clinical proteinuria in individuals with both type 1 and type 2 diabetes and incipient nephropathy. However, small trials on patients with type 2 diabetes and overt nephropathy failed to demonstrate a specific renoprotective role for this class of drugs. The aim of the Program for Irbesartan Mortality and Morbidity Evaluation was to ascertain whether angiotensin II receptor blockers are effective in both preventing the development of clinical proteinuria and delaying the progression of nephropathy in type 2 diabetes. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) Study showed that, as compared with conventional therapy, irbesartan is better at preventing the development of clinical proteinuria and at restoring normoalbuminuria for comparable BP control in patients with incipient nephropathy. The Irbesartan Diabetic Nephropathy Trial showed that irbesartan is more effective than traditional antihypertensive therapies in reducing the progression toward ESRD in patients with type 2 diabetes and overt nephropathy regardless of changes in BP. Moreover, secondary analysis of the Irbesartan Diabetic Nephropathy Trial showed that the achieved systolic pressure as well as baseline and current proteinuria significantly predict renal outcomes. In conclusion, the results of the Program for Irbesartan Mortality and Morbidity Evaluation demonstrate that irbesartan significantly prevents the development of clinical proteinuria in individuals with microalbuminuria and delays the progression of nephropathy in individuals with proteinuria. Moreover, the renoprotective effects of irbesartan go beyond its effect on BP.
Cardiographic Observations on a Fin-Back Whale
Authors: ALFRED W. SENFT, JOHN K. KANWISHER
Journal: Circulation Research (1960)

The beaching of a 40-ton fia-back whale on a Provincetown shore provided a fortuitous opportunity for taking the first cardiograms of the largest mammal. A representative 15-lead cardiogram is shown. This does not differ materially from other large mammals, except that the time scale of events is extremely prolonged. Abnormal foci of ventricular beats and compensatory pauses are illustrated.
Sport and exercise headache: Part 1. Prevalence among university students.
Authors: S J Williams, H Nukada
Journal: British Journal of Sports Medicine (1994)

Sport- and exercise-related headaches have been recognized over the last 20 years, but their prevalence is unknown. A nine-page questionnaire was used to study the prevalence of sports headaches among two contrasting populations of Otago University students: medical students (n = 178) and physical education students (n = 190). Both populations had a similar response rate of approximately 80%. It was found that 35% of respondents had experienced sport- and exercise-related headaches among the two populations, with similar rates for men and women seen in both. Comparison of the two populations showed no significant difference in the rate of sports headache among women, whereas the men physical education students has a significantly higher rate of sports headache than the men medical students. A high frequency of trauma-related headaches in contact sports accounted for this higher rate among the men physical education students. This study demonstrated that sport-and exercise-related headaches are a common problem among university students.
Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer
Authors: Joachim Weischenfeldt, Ronald Simon, Lars Feuerbach, Karin Schlangen, Dieter Weichenhan, Sarah Minner, Daniela Wuttig, Hans-Jörg Warnatz, Henning Stehr, Tobias Rausch, Natalie Jäger, Lei Gu, Olga Bogatyrova, Adrian M. Stütz, Rainer Claus, Jürgen Eils, Roland Eils, Clarissa Gerhäuser, Po-Hsien Huang, Barbara Hutter, Rolf Kabbe, Christian Lawerenz, Sylwester Radomski, Cynthia C. Bartholomae, Maria Fälth, Stephan Gade, Manfred Schmidt, Nina Amschler, Thomas Haß, Rami Galal, Jovisa Gjoni, Ruprecht Kuner, Constance Baer, Sawinee Masser, Christof von Kalle, Thomas Zichner, Vladimir Benes, Benjamin Raeder, Malte Mader, Vyacheslav Amstislavskiy, Meryem Avci, Hans Lehrach, Dmitri Parkhomchuk, Marc Sultan, Lia Burkhardt, Markus Graefen, Hartwig Huland, Martina Kluth, Antje Krohn, Hüseyin Sirma, Laura Stumm, Stefan Steurer, Katharina Grupp, Holger Sültmann, Guido Sauter, Christoph Plass, Benedikt Brors, Marie-Laure Yaspo, Jan O. Korbel, Thorsten Schlomm
Journal: Cancer Cell (2013)
Developmental Separation of V(D)J Recombinase Expression and Initiation of IgH Recombination in B Lineage Progenitors In Vivo
Authors: Lisa Borghesi, Rachel M. Gerstein
Journal: The Journal of Experimental Medicine (2004)

In B lineage progenitors, V(D)J recombination occurs only during distinct stages of development and is restricted to immunoglobulin loci. This process is thought to be controlled by both regulated expression of the V(D)J recombinase and by limited accessibility of target loci to the recombinase complex. However, it is unknown whether these two processes occur concomitantly in developing B lineage progenitors or whether these events are temporally distinct and, therefore, potentially independently regulated. To distinguish between these possibilities, we developed a transgenic V(D)J recombination substrate that is not governed by the same chromatin remodeling constraints as endogenous immunoglobulin heavy chain (IgH) loci and examined the requirements for V(D)J recombination to initiate in early B lineage progenitors. We find that single B lineage precursors express an active V(D)J recombinase in vivo before the stage when IgH rearrangements are frequently detectable. Our results indicate that the onset of recombinase activity and the initiation of IgH recombination are developmentally distinct events in the B lineage.
Assays of Leukocyte Chemotaxis
Authors: S H Zigmond, D A Lauffenburger
Journal: Annual Review of Medicine (1986)

A number of disorders of leukocyte motility and chemotaxis have been reported clinically. In this paper we present a rational approach for testing cell populations for a defect in leukocyte migration and for defining the cellular basis of any abnormality observed. The principles and difficulties of individual and population-type assays are discussed.
Marijuana for Drug-Induced Nausea and Vomiting
Authors: Donald L. Sweet
Journal: JAMA (1980)

In 1975 investigators at the Sidney Farber Cancer Institute in Boston became intrigued by reports from some young patients who said that when they were "high" from smoking "pot," they experienced less or none of the severe nausea and vomiting that usually accompanied their cancer chemotherapy treatments. The investigators subsequently developed a protocol to test the antiemetic effects of Δ<sup>9</sup>-tetrahydrocannabinol (THC), the principal mood-altering agent in marijuana. Of the patients receiving THC, 25% did not vomit at all, and 45% experienced a substantial reduction of their vomiting.<sup>1</sup>In a control group that received a placebo, 73% reported no reduction in nausea or vomiting. Those patients who experienced euphoria were the most likely to also experience a reduction in nausea and vomiting. Toxic effects were tolerable, but a few patients suffered paranoid ideation, feelings of terror, panic, and visual hallucinations. Nevertheless, the Sidney Farber study provoked renewed interest
Successful treatment of inflammatory knee osteoarthritis with tumour necrosis factor blockade
Authors: M Grunke
Journal: Annals of the Rheumatic Diseases (2006)

Increasing evidence indicates that tumour necrosis factor (TNF) has an important role not only in inflammatory arthritis but also in degenerative joint disease.1–3 TNF controls the homoeostasis of matrix synthesis and matrix degeneration in articular cartilage in concert with other cytokines, such as interleukin 1 (IL1), transforming growth factor β, or insulin-like growth factor 1. Overproduction of TNF and IL1 skews the balance towards matrix degradation, at least in part by virtue of induction of nitric oxide synthesis and subsequent metalloproteinase production. In osteoarthritis (OA), increased TNF production by activated synoviocytes and articular chondrocytes together with increased p55 TNF receptor expression on chondrocytes imply the contribution of TNF mediated matrix degradation to disease …
Next-Generation Medicine: Combining BCR-ABL and Hedgehog-Targeted Therapies
Authors: Kim-Hien T. Dao, Jeffrey W. Tyner
Journal: Clinical Cancer Research (2013)

Disease relapse remains a major cause of death in patients with BCR-ABL-positive leukemia despite advances in treatment with kinase inhibitors. Significant efforts are underway to target pathways that maintain leukemia stem cells. Targeting these pathways holds promise for definitive leukemia eradication or improvement of the effectiveness of currently available therapies.
Antileukotriene Agents for the Treatment of Lung Disease
Authors: Jacob P. Scott, Marc Peters-Golden
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Leukotrienes (LTs) C4, D4, and E4, collectively termed cysteinyl LTs (cysLTs), are lipid mediators formed by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. Originally recognized for their potent bronchoconstrictor actions, they were subsequently determined also to promote inflammation, microvascular permeability, and mucus secretion. These actions that are so central to asthma pathophysiology are mediated to a significant extent by ligation of the cysLT receptor 1 (CysLT1). Antagonism of CysLT1 and inhibition of 5-LO have both been shown to have clinical use in the management of asthma, but substantial interindividual heterogeneity is observed in the response to these agents. In this article, we review the biologic actions of LTs, their biosynthetic pathways and cognate receptors, the pharmacology of available anti-LT agents, and the clinical evidence for the use of anti-LT agents as monotherapy and combination therapy in asthma. We also consider heterogeneity of response, the possible roles of cysLT receptors other than CysLT1, the role of another class of LT, LTB4, and the potential role of LTs in lung diseases other than asthma.
Retinal Microvascular Abnormalities and Renal Dysfunction
Authors: Tien Yin Wong, Josef Coresh, Ronald Klein, Paul Muntner, David J. Couper, A. Richey Sharrett, Barbara E.K. Klein, Gerardo Heiss, Larry D. Hubbard, Bruce B. Duncan
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Microvascular disease has been linked with renal dysfunction in patients with diabetes. The aim of this study was to examine the association of retinal microvascular abnormalities to renal dysfunction among participants of the Atherosclerosis Risk in Communities Study, a population-based investigation in four U.S. communities. At the third examination (1993 to 1995), retinal photography was performed and the presence of retinal microvascular abnormalities was documented using a standard grading protocol. Renal dysfunction was defined as an increase in serum creatinine of at least 0.4 mg/dl or a death or hospitalization as a result of chronic kidney disease between the second (1990 to 1992) and fourth (1996 to 1998) examinations. Among 10,056 people who were included in the study, 270 (2.7%) developed renal dysfunction. After controlling for age, gender, race, diabetes, BP, and other risk factors, individuals with retinopathy (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 2.8), microaneurysms (OR, 2.0; 95% CI, 1.3 to 3.1), retinal hemorrhages (OR, 2.6; 95% CI, 1.6 to 4.0), soft exudates (OR, 2.7; 95% CI, 1.6 to 4.8), and arteriovenous nicking (OR, 1.4; 95% CI, 1.0 to 1.9) were more likely to develop renal dysfunction than individuals without these abnormalities. Retinal microvascular abnormalities are associated with renal dysfunction, suggesting that common systemic microvascular processes may underlie the development of microvascular damage in the eye and kidneys.
Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens.
Authors: H D McIntyre, C A Mitchell, S D Bowler, J G Armstrong, J A Wooler, D M Cowley
Journal: Thorax (1995)

BACKGROUND--Inhaled glucocorticoid therapy has systemic effects including hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting these effects has not been defined. METHODS--Timed urine collections and 09.00 hour plasma cortisol levels were obtained from 12 normal volunteers receiving inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour urine samples were collected as follows: first hour after waking (hour 1), the next two hours after waking (hours 2 and 3), remainder of day, and overnight, with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly cortisol output in the timed collections. Twenty four hour urinary cortisol excretion was also calculated. Medication was blinded and given in random order with a washout period of at least 11 days between each treatment arm. RESULTS--None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1, hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the plasma cortisol level did not change significantly. Cortisol output showed similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC ratios for the first two hours after waking. CONCLUSIONS--UCC ratios are as sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and more sensitive than single morning plasma cortisol measurements, in detecting the effects of inhaled beclomethasone on the HPA axis.
Factor V Leiden is not common in patients diagnosed with primary pulmonary hypertension
Authors: CG Elliott, MF Leppert, GJ Alexander, K Ward, L Nelson, GG Pietra
Journal: European Respiratory Journal (1998)

Substantial evidence suggests that thrombosis contributes to the pathogenesis of primary pulmonary hypertension (PPH). An abnormal factor V (factor V Leiden) may contribute to thrombosis in the pulmonary microcirculation of PPH patients. A point mutation in which adenine is substituted for guanine at nucleotide 1691 (1691A) alters factor V so that it resists cleavage by activated protein C. Heterozygosity for the 1691A mutation is more common (2-8%) in Caucasian Europeans and Americans than in Africans (1%) and Asians (&lt;1%). The aim of the study was to examine the prevalence of the mutation that codes for factor V Leiden in individuals with PPH. We identified 42 Caucasians diagnosed with PPH. We extracted deoxyribonucleic acid (DNA) from whole blood and assayed DNA samples for the point mutation (1691 A) that codes for factor V Leiden. One out of 42 (2.4%; 95% confidence interval=0.1-12.6) Caucasians diagnosed with PPH was heterozygous for the normal 1691G and mutant 1691A allele. All 10 individuals with familial PPH were homozygous for the normal 1691G allele. The prevalence of heterozygosity for the 1691A allele and the normal 1691G allele does not differ from that observed in reference (control) populations. The low prevalence of the 1691A mutation among individuals diagnosed with primary pulmonary hypertension provides evidence that factor V Leiden does not contribute to the pathogenesis of the disease in most patients.
Lung volume reduction surgery for emphysema
Authors: EW Russi, U Stammberger, W Weder
Journal: European Respiratory Journal (1997)

Lung volume reduction surgery (LVRS) is performed to alleviate dyspnoea of selected patients with severe pulmonary emphysema and to improve their pulmonary function, performance in daily activity and quality of life. By resection of destroyed lung areas the achievable improvements in function may consist of: 1) a reduction in hyperinflation resulting in amelioration of diaphragm and chest wall mechanics; 2) an increase of elastic recoil pressure, thereby augmenting expiratory flow rates; and 3) possibly an improvement in gas exchange. Meticulous selection of suitable patients, refinements in operative techniques, anaesthesiological and postoperative management has lowered perioperative mortality to less than 5% in groups who are experienced with this type of procedure. The best functional results are achieved by bilateral resection, which can either be performed by median sternotomy or by video-assisted thoracoscopy (VAT). The average increase in forced expiratory volume in one second (FEV1), obtained by bilateral resection in patients already receiving optimal medical therapy ranges 32-93%, and the reduction in hyperinflation, assessed by a decrease in total lung capacity ranges 15-20%. These favourable improvements have been reported to last in most of the patients for at least one year.
Petrolatum: interference with the oxidation of arachidonic acid
Authors: NEAL S. PENNEYS, WILLIAM EAGLSTEIN, VINCENT ZIBOH
Journal: British Journal of Dermatology (1980)

Journal Article Petrolatum: interference with the oxidation of arachidonic acid Get access NEAL S. PENNEYS, NEAL S. PENNEYS Department of Dermatology, University of Miami School of Medicine, Miami, U. S. A. Dr Neal S. Penneys, Department of Dermatology, R‐11, University of Miami School of Medicine, Box 016940, Miami, F1, 33101, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar WILLIAM EAGLSTEIN, WILLIAM EAGLSTEIN Department of Dermatology, University of Miami School of Medicine, Miami, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar VINCENT ZIBOH VINCENT ZIBOH Department of Dermatology, University of Miami School of Medicine, Miami, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 103, Issue 3, 1 September 1980, Pages 257–262, https://doi.org/10.1111/j.1365-2133.1980.tb07242.x Published: 01 September 1980
Api6/AIM/Spα/CD5L Overexpression in Alveolar Type II Epithelial Cells Induces Spontaneous Lung Adenocarcinoma
Authors: Yuan Li, Peng Qu, Lingyan Wu, Beilin Li, Hong Du, Cong Yan
Journal: Cancer Research (2011)

Abstract Chronic inflammation is an important contributor to the development of lung cancers, one of the most common malignancies worldwide, but the underlying molecular mechanisms of inflammation that specifically cue cancer risk remain poorly understood. Apoptosis inhibitor 6 (Api6, also known as AIM, Sp-α, and CD5L) is a downstream target gene of neutral lipids and peroxisome proliferator–activated receptor gamma in lung alveolar type II (AT II) epithelial cells. An association among increased expression of Api6 in certain settings of pathogenic lung inflammation in mice prompted us to hypothesize a possible role in cancer. Here, we report that Api6 promotes malignant transformation by limiting lung epithelial cell apoptosis and promoting immune escape. The specific function of Api6 in AT II cells was determined by using a doxycycline-inducible Api6 mouse model. Api6 overexpression inhibited apoptosis and activated oncogenic signaling in AT II lung epithelial cells, inducing emphysema and adenocarcinoma. In addition, Api6 overexpression in AT II cells increased the concentrations of proinflammatory cytokines/chemokines in bronchoalveolar lavage fluid and serum, promoting expansion of myeloid-derived suppressor cells (MDSC) in lung and blood but not in bone marrow or spleen. Lung MDSCs suppressed T-cell proliferation and activity in vitro and reduced levels of T cells in vivo following doxycycline treatment to activate Api6. Together, our findings establish that Api6 promotes lung tumorigenesis by blocking a mechanism of epithelial apoptosis that would normally support immunosurveillance. Cancer Res; 71(16); 5488–99. ©2011 AACR.
Disorders of the Respiratory Muscles
Authors: Franco Laghi, Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Section:ChooseTop of pageAbstract <<CONTENTSCHRONIC OBSTRUCTIVE PULMO...ASTHMACHRONIC HEART FAILUREACUTE RESPIRATORY FAILURENEUROMUSCULAR DISEASESRESTRICTIVE DISEASESSYSTEMIC DISEASESCONSEQUENCES OF SURGERYReferencesCITING ARTICLES