tbuckley/cabot-search huggingface dataset:
Platelet function in patients with obstructivesleep apnoea syndrome
Authors: B.M. Sanner, M. Konermann, M. Tepel, J. Groetz, C. Mummenhoff, W. Zidek
Journal: European Respiratory Journal (2000)

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.
Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction.
Authors: E Loh, J S Stamler, J M Hare, J Loscalzo, W S Colucci
Journal: Circulation (1994)

BACKGROUND Pulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension. METHODS AND RESULTS To test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P &lt; .001) due to a 23 +/- 7% increase (P &lt; .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P &lt; .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was inversely related (r = -.713; P &lt; .001) to the baseline PVR. Inhaled NO had no effect on heart rate, systemic arterial pressure, systemic vascular resistance, or LV peak +dP/dt or -dP/dt. CONCLUSIONS In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure. These findings predict that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure.
Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial
Authors: Alexander MM Eggermont, Stefan Suciu, Rona MacKie, Wlodzimierz Ruka, Alessandro Testori, Wim Kruit, Cornelis JA Punt, Michelle Delauney, François Sales, Gerard Groenewegen, Dirk J Ruiter, Izabella Jagiello, Konstantin Stoitchkov, Ulrich Keilholz, Danielle Lienard
Journal: The Lancet (2005)
Trends in the Timing of Pre-emptive Kidney Transplantation
Authors: Morgan E. Grams, Allan B. Massie, Josef Coresh, Dorry L. Segev
Journal: Journal of the American Society of Nephrology (2011)

Pre-emptive kidney transplantation is considered the best available renal replacement therapy, but no guidelines exist to direct its timing during CKD progression. We used a national cohort of 19,471 first-time pre-emptive kidney transplant recipients between 1995-2009 to evaluate patterns and implications of transplant timing. Mean estimated GFR (eGFR) at the time of pre-emptive transplant increased significantly over time, from 9.2 ml/min/1.73 m(2) in 1995 to 13.8 ml/min/1.73 m(2) in 2009 (P<0.001). Patients with eGFR ≥ 15 ml/min/1.73 m(2) represented an increasing proportion of pre-emptive transplant recipients, from 9% in 1995 to 35% in 2009; the trend for patients with eGFR ≥ 10 was similar (30% to 72%). We did not detect statistically significant differences in patient survival or death-censored graft survival between strata of eGFR at the time of transplant, either in the full cohort or in subgroup analyses of patients who might theoretically benefit from earlier pre-emptive transplantation. In summary, pre-emptive kidney transplantation is occurring at increasing levels of native kidney function. Earlier transplantation does not appear to associate with patient or graft survival, suggesting that earlier pre-emptive transplantation may subject donors and recipients to premature operative risk and waste the native kidney function of recipients.
Improving outcomes from acute upper gastrointestinal bleeding: Table 1
Authors: Vipul Jairath, Alan N Barkun
Journal: Gut (2012)

Upper gastrointestinal bleeding (UGIB) is predominantly non-variceal in origin and remains one of the most common challenges faced by gastroenterologists and endoscopists in daily clinical practice. Despite major advances in the approach to the management of non-variceal upper gastrointestinal bleeding (NVUGIB) over the past decade including prevention of peptic ulcer bleeding, optimal use of endoscopic therapy1 and high-dose proton pump inhibition,2 it still carries considerable morbidity, mortality and health economic burden. Although many modernised healthcare systems report reductions in case death over time,3–5 most likely attributable to the aforementioned advances in addition to general supportive care, mortality remains appreciably high. Of particular note, rebleeding rates—one of the most important predictive factors of mortality and arguably the best reflection of interventions directly targeted at bleeding—have not significantly improved from longitudinal data in the past 15 years.6 7 In addition to high-quality trials that have informed best evidence-based practice guidelines in recent years,8 we have been provided with a plethora of detailed ‘real-life’ outcome data from multicentre observational studies of UGIB originating from Canada (RUGBE,9 REASON10 AND REASON-211), Italy (PNED-112 and PNED-213) and the UK,14 enabling an assessment of how well such guidelines are adhered to and serving to highlight deficiencies in existing aspects of care which could be improved upon. These studies are further described in table 1.

View this table:

Table 1 
Description of study designs and inclusion criteria



Using data from published papers of the aforementioned studies, we highlight a number of areas in the management of NVUGIB where efforts could be targeted to improve existing shortcomings in care. In addition we provide suggestions for parameters upon which improvements in care may be monitored in longitudinal studies as well as highlighting key areas for …
Control of breathing in mechanically ventilated patients
Authors: D Georgopoulos, C Roussos
Journal: European Respiratory Journal (1996)

During mechanical ventilation, the respiratory system is under the influence of two pumps, the ventilator pump and the patient's own respiratory muscles. Depending on the mode of mechanical ventilatory support, ventilation may be totally controlled by the ventilator or may be determined by the interaction between patient respiratory effort and ventilator function. In either case, compared to spontaneous breathing, the breathing pattern is altered and this may influence: 1) force-length and force-velocity relationships of respiratory muscles (mechanical feedback); 2) chemical stimuli (chemical feedback); 3) the activity of various receptors located in the respiratory tract, lung and chest wall (reflex feedback); and 4) behavioural response (behavioural feedback). Changes in these feedback systems may modify the function of the ventilator, in a way that is dependent on the mode of mechanical ventilatory support, ventilator settings, mechanics of the respiratory system and the sleep/awake stage. Thus, the response of ventilator to patient effort, and that of patient effort to ventilator-delivered breath are inevitably the two components of control of breathing during mechanical ventilation; the ventilatory output is the final expression of the interaction between these two components. As a result of this interaction, the various aspects of control of breathing of the respiratory system may be masked or modulated by mechanical ventilation, depending on several factors related both to patient and ventilator. This should be taken into consideration in the management of mechanically ventilated patients.
Plasmacytoid Dendritic Cells, Interferon Signaling, and FcγR Contribute to Pathogenesis and Therapeutic Response in Childhood Immune Thrombocytopenia
Authors: Kartik Sehgal, Xiuyang Guo, Srinivas Koduru, Anumeha Shah, Aiping Lin, Xiting Yan, Kavita M. Dhodapkar
Journal: Science Translational Medicine (2013)

Targeting plasmacytoid dendritic cells or blockade of interferon response may benefit patients with an autoimmune disease against platelets.
TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator
Authors: Ya-Ping Tsai, Hsiao-Fan Chen, Sung-Yuan Chen, Wei-Chung Cheng, Hsei-Wei Wang, Zih-Jie Shen, Chunxiao Song, Shu-Chun Teng, Chuan He, Kou-Juey Wu
Journal: Genome biology (2014)

Abstract Background Hypoxia induces the epithelial-mesenchymal transition, EMT, to promote cancer metastasis. In addition to transcriptional regulation mediated by hypoxia-inducible factors, HIFs, other epigenetic mechanisms of gene regulation, such as histone modifications and DNA methylation, are utilized under hypoxia. However, whether DNA demethylation mediated by TET1, a DNA dioxygenase converting 5-methylcytosine, 5mC, into 5-hydroxymethylcytosine, 5hmC, plays a role in hypoxia-induced EMT is largely unknown. Results We show that TET1 regulates hypoxia-responsive gene expression. Hypoxia/HIF-2α regulates the expression of TET1. Knockdown of TET1 mitigates hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes. Cholesterol metabolic process genes are among the genes that showed high prevalence and statistical significance. We characterize one of the genes, INSIG1 (insulin induced gene 1), to confirm its expression and the 5hmC levels in its promoter. Knockdown of INSIG1 also mitigates hypoxia-induced EMT. Finally, TET1 is shown to be a transcriptional co-activator that interacts with HIF-1α and HIF-2α to enhance their transactivation activity independent of its enzymatic activity. TET1 acts as a co-activator to further enhance the expression of INSIG1 together with HIF-2α. We define the domain in HIF-1α that interacts with TET1 and map the domain in TET1 that confers transactivation to a 200 amino acid region that contains a CXXC domain. The TET1 catalytically inactive mutant is capable of rescuing hypoxia-induced EMT in TET1 knockdown cells. Conclusions These findings demonstrate that TET1 serves as a transcription co-activator to regulate hypoxia-responsive gene expression and EMT, in addition to its role in demethylating 5mC.
Features of Neuromyelitis Optica Spectrum Disorders and Aquaporin-4 With Myelin-Oligodendrocyte Glycoprotein Antibodies—Reply
Authors: Joanna Kitley, Patrick Waters, Angela Vincent, Jacqueline Palace
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Estrogens and Glucocorticoids Inhibit Endothelial Vascular Cell Adhesion Molecule-1 Expression by Different Transcriptional Mechanisms
Authors: Tommaso Simoncini, Silvia Maffei, Giuseppina Basta, Giuseppina Barsacchi, Andrea R. Genazzani, James K. Liao, Raffaele De Caterina
Journal: Circulation Research (2000)

Abstract —The antiatherogenic effect of estrogen is mediated, in part, by inhibitory effects on endothelial vascular cell adhesion molecule-1 (VCAM-1) expression. To determine the mechanism by which estrogen regulates VCAM-1 expression, we compared the effect of 17β-estradiol (E 2 ) and of the glucocorticoid dexamethasone (Dex) on lipopolysaccharide (LPS)–induced VCAM-1 expression in human endothelial cells. E 2 decreased LPS-induced VCAM-1 mRNA and protein expression to a greater extent than Dex. Dex, but not E 2 , stabilized VCAM-1 mRNA. This correlated with inhibition of monocytoid U937 cell adhesion to endothelial cells. Transfection of endothelial cells with a functional VCAM-1 promoter construct showed that E 2 inhibited LPS-induced VCAM-1 gene transcription more potently than did Dex. However, using a truncated construct containing only the nuclear factor-κB (NF-κB)–responsive elements but lacking the consensus sequences for activator protein-1 (AP-1) and GATA, E 2 and Dex had similar inhibitory effects. Consistently, gel-shift assays showed that E 2 and Dex comparably inhibit LPS-induced activation of NF-κB, whereas E 2 inhibited LPS-induced activation of AP-1 and GATA to a greater extent than Dex. E 2 inhibition of NF-κB after LPS treatment was associated with decreased inhibitor κB (IκB) kinase activity and with a stabilization of the NF-κB inhibitor IκBα. These results indicate that E 2 decreases VCAM-1 gene expression through the inhibition of NF-κB, AP-1, and GATA and suggest novel mechanisms for the antiatherogenic effect of estrogen on the vascular wall. ( Circ Res. 2000;87:19-25.)
Adjuvant Therapy for Premenopausal Women With Breast Cancer: Is It Time for Another Paradigm Shift?
Authors: Kathleen I. Pritchard
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.24.4611 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12488402 Adjuvant Therapy for Premenopausal Women With Breast Cancer: Is It Time for Another Paradigm Shift? Kathleen I. PritchardxKathleen I. PritchardSearch for articles by this author Show More Toronto Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada https://doi.org/10.1200/JCO.2002.20.24.4611 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
THE MAMMALIAN CARBOXYLESTERASES: From Molecules to Functions
Authors: Tetsuo Satoh, Masakiyo Hosokawa
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract Multiple carboxylesterases (EC 3.1.1.1) play an important role in the hydrolytic biotransformation of a vast number of structurally diverse drugs. These enzymes are major determinants of the pharmacokinetic behavior of most therapeutic agents containing ester or amide bonds. Carboxylesterase activity can be influenced by interactions of a variety of compounds either directly or at the level of enzyme regulation. Since a significant number of drugs are metabolized by carboxylesterase, altering the activity of this enzyme class has important clinical implications. Drug elimination decreases and the incidence of drug-drug interactions increases when two or more drugs compete for hydrolysis by the same carboxylesterase isozyme. Exposure to environmental pollutants or to lipophilic drugs can result in induction of carboxylesterase activity. Therefore, the use of drugs known to increase the microsomal expression of a particular carboxylesterase, and thus to increase associated drug hydrolysis capacity in humans, requires caution. Mammalian carboxylesterases represent a multigene family, the products of which are localized in the endoplasmic reticulum of many tissues. A comparison of the nucleotide and amino acid sequence of the mammalian carboxylesterases shows that all forms expressed in the rat can be assigned to one of three gene subfamilies with structural identities of more than 70% within each subfamily. Considerable confusion exists in the scientific community in regards to a systematic nomenclature and classification of mammalian carboxylesterase. Until recently, adequate sequence information has not been available such that valid links among the mammalian carboxylesterase gene family or evolutionary relationships could be established. However, sufficient basic data are now available to support such a novel classification system.
Heart Failure and the Ryanodine Receptor
Authors: D.A. Eisner, A.W. Trafford
Journal: Circulation Research (2002)

In heart failure, the amplitude and rate of decay of both contraction and the underlying systolic Ca 2ϩ transient are reduced.A current debate concerns the mechanism of these alterations of calcium handling.One theory invokes decreased activity of the sarcoplasmic reticulum (SR) Ca 2ϩ -ATPase (SERCA) 1 while another focuses on alterations in the SR Ca 2ϩ release channel (ryanodine receptor, RyR). 2 A significant contribution to this debate is made by Jiang et al 3 in this issue of Circulation Research.
Animal Versus Plant Protein Meals in Individuals With Type 2 Diabetes and Microalbuminuria
Authors: Madelyn L. Wheeler, S. Edwin Fineberg, Naomi S. Fineberg, Reid G. Gibson, Laurie L. Hackward
Journal: Diabetes Care (2002)

OBJECTIVE—To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure. RESEARCH DESIGN AND METHODS—In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit. RESULTS—There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA1c, blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P &amp;lt; 0.01), HbA1c had significantly improved (PP: from 8.1 to 7.5%, P &amp;lt; 0.01; AP: from 7.9 to 7.4%, P &amp;lt; 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P &amp;lt; 0.02; AP: from 82 to 78, P &amp;lt; 0.02). CONCLUSIONS—There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source.
Affective Disorder in Juvenile Offenders: A Preliminary Study
Authors: S R Pliszka, J O Sherman, M V Barrow, S Irick
Journal: American Journal of Psychiatry (2000)

The authors' goal was to determine the prevalence of major mental disorders and substance abuse in adolescents admitted to a juvenile detention center.As part of a routine mental health screening, modules from the Diagnostic Interview Schedule for Children were administered to 50 youths (11-17 years old) at an urban juvenile detention center.A high rate of affective disorder (42%) was found among these adolescents: 10 (20%) met criteria for mania, another 10 met criteria for major depressive disorder, and one met criteria for bipolar disorder, mixed type. Thirty (60%) met criteria for conduct disorder, and very high rates of alcohol, marijuana, and other substance dependence were found. There was a strong association between affective disorder and conduct disorder; adolescents with mania had much higher rates of reported abuse of substances other than alcohol or marijuana.Juvenile offenders have high rates of affective disorder. Further studies are needed to examine the relationship of affective disorder to substance abuse as well as to antisocial behavior.
Assessment of Energy Expenditure and Fuel Utilization in Man
Authors: E Jequier, K Acheson, Y Schutz
Journal: Annual Review of Nutrition (1987)

DIRECT AND INDIRECT CALORIMETRY .. . . . .... . . . . ... . . ..... . . . ..... . ..... . ..... . . ..... . 1 87 Introduction  1 87 Heat Balance Equation     ......   188 Direct Calorimetry  . . . . ...... . ....... ...... . . . .. . . . . . . . . . . . . . . . ... . . . .. ..... .... 1 89 Indirect Calorimetry..... . . . . . . . . . . . . . . . . . .. . . . ..... . ... . . . . . . . . . . ... . . . . . . . . . . . . . . . . . ... . . . ...... 190 Indirect Calormietry with a Respiration Chamber   192 FUEL UTILIZATION IN MAN . . . ..... . .   . . ..... . ....... .... . ....... ..... . ...... ... . . 193 Theoretical Limitations ..... . . . .. ..... ... . . . ..... . . . .... . . .... . . .   . . .... . . .... . ..... .... 195 Physiological Considerations. .. . ........ . . . .... . ..... . . ..... . . .. . . . . .... . ..... . .... . . ...... .... 196 Stoichiometry .. . . ... .   . . . . ... . . ........ . ... ...... ..... . . ..... ..... ......... . . ... . .... . . 200 NONCALORIMETRIC METHODS WITH REFERENCE TO THE 2H2180 TECHNIQUE . . . . . . . . . . .. . . . . ..... . . ..... . . ..... . . ... . . . ... . . . .... . .. . . . . ... . . ... . . . . ... . . 203