tbuckley/cabot-search huggingface dataset:
Serum prostacyclin binding defects in thrombotic thrombocytopenic purpura.
Authors: K K Wu, E R Hall, E C Rossi, A C Papp
Journal: Journal of Clinical Investigation (1985)

To understand the pathophysiologic significance of abnormal serum prostacyclin (PGI2) binding activities in thrombotic thrombocytopenic purpura (TTP), we evaluated the PGI2 binding characteristics in three chronic TTP sera and 19 normal sera. PGI2 binding by serum was rapid and reversible. The binding activity in TTP sera (22.1 +/- SD, 4.4%) was significantly lower than that of normal sera (42.2 +/- 6.2%). Moreover, the antiaggregating activity and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) content in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum. Although normal and TTP sera bound [14C]arachidonate with similar activity, and neither bound [3H]6KPGF1 alpha, there was a difference in prostaglandin E1 (PGE1) binding. Binding of [3H]PGE1 was subnormal in two TTP sera (W.J. and T.G.) and normal in the third (H.S.). Normal serum corrected the binding defects of TTP serum. Interestingly, the mixture of two TTP sera (W.J. and H.S.) mutually corrected their PGI2 binding defects. In addition, although in vivo plasma transfusions improved the PGI2 binding activity of W.J. and H.S., there existed a striking difference in the nature of their response. These observations indicate that there is at least two types of PGI2 binding defects in TTP. Our data indicate that TTP is associated with diminished serum binding of PGI2. This defect may reduce the availability of PGI2 to damaged vascular sites and decrease an important modulator of platelet thrombus formation at times of severe vascular insult.
Dose-Escalated Radiotherapy for Prostate Cancer
Authors: Phillip J. Gray, Anthony L. Zietman
Journal: JAMA Oncology (2015)

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 Oncology 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 Oncology journal
TV Viewing and Physical Activity Are Independently Associated with Metabolic Risk in Children: The European Youth Heart Study
Authors: Ulf Ekelund, Søren Brage, Karsten Froberg, Maarike Harro, Sigmund A Anderssen, Luis B Sardinha, Chris Riddoch, Lars Bo Andersen
Journal: PLoS Medicine (2006)

Background TV viewing has been linked to metabolic-risk factors in youth. However, it is unclear whether this association is independent of physical activity (PA) and obesity. Methods and Findings We did a population-based, cross-sectional study in 9- to 10-y-old and 15- to 16-y-old boys and girls from three regions in Europe (n = 1,921). We examined the independent associations between TV viewing, PA measured by accelerometry, and metabolic-risk factors (body fatness, blood pressure, fasting triglycerides, inverted high-density lipoprotein (HDL) cholesterol, glucose, and insulin levels). Clustered metabolic risk was expressed as a continuously distributed score calculated as the average of the standardized values of the six subcomponents. There was a positive association between TV viewing and adiposity (p = 0.021). However, after adjustment for PA, gender, age group, study location, sexual maturity, smoking status, birth weight, and parental socio-economic status, the association of TV viewing with clustered metabolic risk was no longer significant (p = 0.053). PA was independently and inversely associated with systolic and diastolic blood pressure, fasting glucose, insulin (all p < 0.01), and triglycerides (p = 0.02). PA was also significantly and inversely associated with the clustered risk score (p < 0.0001), independently of obesity and other confounding factors. Conclusions TV viewing and PA may be separate entities and differently associated with adiposity and metabolic risk. The association between TV viewing and clustered metabolic risk is mediated by adiposity, whereas PA is associated with individual and clustered metabolic-risk indicators independently of obesity. Thus, preventive action against metabolic risk in children may need to target TV viewing and PA separately.
Flitting radiographic shadows: an unusual presentation of cancer in the lungs
Authors: W M Edmondstone
Journal: Thorax (1998)

Tumour involvement of pulmonary blood vessels occurs frequently in advanced lung cancer and occasionally may cause pulmonary infarction. A case is reported of diffuse obstruction of pulmonary arteries by cancer in which no primary tumour was found, and which presented as flitting radiographic opacities due to pulmonary infarction.
Rat intestinal apolipoprotein B gene expression. Evidence for integrated regulation by bile salt, fatty acid, and phospholipid flux.
Authors: N O Davidson, M J Drewek, J I Gordon, J Elovson
Journal: Journal of Clinical Investigation (1988)

We previously reported that intestinal apo B48 synthesis in the rat was unaltered by dietary triglyceride intake but demonstrated regulation in response to biliary lipid availability. Studies are now presented in which the mechanisms underlying biliary lipid dependent expression of intestinal apo B48 synthesis have been investigated further. Bile salt replacement was effective in a dose- and structure-dependent manner in reexpressing intestinal apo B48 synthesis after prolonged bile diversion. Further experiments suggested that this effect of bile salt may be related to facilitated uptake of fatty acid. A role for mucosal phospholipid flux was suggested by studies in which infusion of lysolecithin, with or without Na taurocholate, produced complete reexpression of apo B48 synthesis in jejunal enterocytes. Over a four- to sixfold range of apo B48 synthesis rates in both jejunum and ileum, there was no change in apo B mRNA size or abundance as determined by RNA blot hybridization. Analysis of both intestinal mucosa and microsome lipid content in a variety of settings revealed that apo B48 synthesis rates were correlated with microsome triglyceride fatty acid content (r = 0.65, P less than 0.005) but not free fatty acid or phospholipid content. These studies demonstrate a physiologic role for elements of biliary lipid flux in the regulation of apo B gene expression. The data suggest that an integrated mechanism may exist whereby apo B48 synthesis is related to microsome triglyceride flux, particularly at low levels of lumenal substrate availability.
Splanchnic and renal elimination and release of catecholamines in cirrhosis. Evidence of enhanced sympathetic nervous activity in patients with decompensated cirrhosis.
Authors: J H Henriksen, H Ring-Larsen, I L Kanstrup, N J Christensen
Journal: Gut (1984)

Plasma noradrenaline (NA) and adrenaline (A) concentrations were determined in different vascular areas in 32 patients with cirrhosis and in nine controls during a right sided heart, liver, and renal vein catheterisation. The patients were divided into four groups: (I) Compensated (without ascites); (II) Recompensated on diuretic treatment because of former ascites; (III) Decompensated (with ascites) without treatment and (IV) Decompensated on diuretic treatment. Median arterial noradrenaline concentrations were 1.48, 1.07, 2.66, 4.14 and 2.50 nmol/l in controls, group I, II, III, and IV, respectively, the three last mentioned values being significantly raised (p less than 0.01). Median arterial adrenaline concentrations were not significantly increased. In patients arterial-hepatic venous extraction ratios of noradrenaline and adrenaline were on the average 25% (p less than 0.01) and 20% (p less than 0.02) less than those of the controls, indicating a slightly reduced splanchnic elimination of catecholamines in cirrhoses. In controls and group I significant renal venous-arterial noradrenaline differences were absent (0.00 and 0.03 nmol/l) while renal venous-arterial noradrenaline differences were significantly increased in groups II, III and IV (0.47, 0.53 and 0.68 nmol/l, p less than 0.01), indicating a significant net release of noradrenaline from the kidneys in recompensated and decompensated patients. Renal extraction of adrenaline was normal. In conclusion, increased arterial noradrenaline in decompensated and recompensated cirrhosis is only to a limited extent owing to reduced net splanchnic elimination. More likely the increase is caused by release of noradrenaline from the kidneys and possibly other organs indicating enhanced sympathetic nervous tone in these conditions.
Reduction of the Cardiac Response to Postganglionic Sympathetic Nerve Stimulation in Experimental Heart Failure
Authors: JAMES W. COVELL, CHARLES A. CHIDSEY, EUGENE BRAUNWALD
Journal: Circulation Research (1966)

The functional significance of the reduction of the heart's norepinephrine stores which occurs in experimental heart failure was studied. The responses to right and left cardio-accelerator nerve stimulation were studied in normal dogs and in dogs with chronic congestive failure and reduced myocardial norepinephrine stores. Both the chronotropic and inotropic responses to nerve stimulation were found to be markedly reduced in the animals with congestive failure. Since the myocardium of the dogs with heart failure responded normally to exogenously administered norepinephrine, it was concluded that the norepinephrine depletion reduces the quantity of neurotransmitter released per nerve impulse. Thus, norepinephrine depletion interferes with the ability of the adrenergic nervous system to support the failing myocardium and in this manner it may intensify the congestive heart failure state.
The Binding Site of Aminergic G Protein–Coupled Receptors: The Transmembrane Segments and Second Extracellular Loop
Authors: Lei Shi, Jonathan A. Javitch
Journal: The Annual Review of Pharmacology and Toxicology (2002)

In the current chapter, we review approaches to the identification of the residues forming the binding sites for agonists, antagonists, and allosteric modulators in the family of aminergic G protein–coupled receptors (GPCRs). We then review the structural bases for ligand binding and pharmacological specificity based on the application of these methods to muscarinic cholinergic, adrenergic, dopaminergic, serotonergic, and histaminergic receptors, using the high resolution rhodopsin structure as a template. Furthermore, we propose a critical role of the second extracellular loop in forming the binding site for small molecular weight aminergic ligands, much as this loop dives down into the binding-site crevice and contacts retinal in rhodopsin.
Cardiovascular Events during World Cup Soccer
Authors: Ute Wilbert-Lampen, David Leistner, Sonja Greven, Tilmann Pohl, Sebastian Sper, Christoph Völker, Denise Güthlin, Andrea Plasse, Andreas Knez, Helmut Küchenhoff, Gerhard Steinbeck
Journal: New England Journal of Medicine (2008)

The Fédération Internationale de Football Association (FIFA) World Cup, held in Germany from June 9 to July 9, 2006, provided an opportunity to examine the relation between emotional stress and the incidence of cardiovascular events.Cardiovascular events occurring in patients in the greater Munich area were prospectively assessed by emergency physicians during the World Cup. We compared those events with events that occurred during the control period: May 1 to June 8 and July 10 to July 31, 2006, and May 1 to July 31 in 2003 and 2005.Acute cardiovascular events were assessed in 4279 patients. On days of matches involving the German team, the incidence of cardiac emergencies was 2.66 times that during the control period (95% confidence interval [CI], 2.33 to 3.04; P<0.001); for men, the incidence was 3.26 times that during the control period (95% CI, 2.78 to 3.84; P<0.001), and for women, it was 1.82 times that during the control period (95% CI, 1.44 to 2.31; P<0.001). Among patients with coronary events on days when the German team played, the proportion with known coronary heart disease was 47.0%, as compared with 29.1% of patients with events during the control period. On those days, the highest average incidence of events was observed during the first 2 hours after the beginning of each match. A subanalysis of serious events during that period, as compared with the control period, showed an increase in the incidence of myocardial infarction with ST-segment elevation by a factor of 2.49 (95% CI, 1.47 to 4.23), of myocardial infarction without ST-segment elevation or unstable angina by a factor of 2.61 (95% CI, 2.22 to 3.08), and of cardiac arrhythmia causing major symptoms by a factor of 3.07 (95% CI, 2.32 to 4.06) (P<0.001 for all comparisons).Viewing a stressful soccer match more than doubles the risk of an acute cardiovascular event. In view of this excess risk, particularly in men with known coronary heart disease, preventive measures are urgently needed.
Treating Acute Stress Disorder: An Evaluation of Cognitive Behavior Therapy and Supportive Counseling Techniques
Authors: Richard A. Bryant, Tanya Sackville, Suzanne T. Dang, Michelle Moulds, Rachel Guthrie
Journal: American Journal of Psychiatry (1999)

Acute stress disorder permits an early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder (PTSD). This study aimed to prevent PTSD by an early provision of cognitive behavior therapy. Specifically, this study indexed the relative efficacy of prolonged exposure and anxiety management in the treatment of acute stress disorder.Forty-five civilian trauma survivors with acute stress disorder were given five sessions of 1) prolonged exposure (N = 14), 2) a combination of prolonged exposure and anxiety management (N = 15), or 3) supportive counseling (N = 16) within 2 weeks of their trauma. Forty-one trauma survivors were assessed at the 6-month follow-up.Fewer patients with prolonged exposure (14%, N = 2 of 14) and prolonged exposure plus anxiety management (20%, N = 3 of 15) than supportive counseling (56%, N = 9 of 16) met the criteria for PTSD after treatment. There were also fewer cases of PTSD in the prolonged exposure group (15%, N = 2 of 13) and the prolonged exposure plus anxiety management group (23%, N = 3 of 13) than in the supportive counseling group (67%, N = 10 of 15) 6 months after the trauma. Chronic PTSD in the supportive counseling condition was characterized by greater avoidance behaviors than in the prolonged exposure condition or the prolonged exposure plus anxiety management condition.These findings suggest that PTSD can be effectively prevented with an early provision of cognitive behavior therapy and that prolonged exposure may be the most critical component in the treatment of acute stress disorder.
Insulin and myocardial blood flow
Authors: J Sundell
Journal: Cardiovascular Research (2003)

The renaissance of glucose–insulin–potassium infusion (GIK) as a treatment of acute myocardial infarction both in diabetic and nondiabetic subjects has raised new interests to clarify the effects and mechanisms of insulin on myocardium. Although the action of insulin on substrate metabolism is quite well studied in heart, the cardiovascular effects were until recent years poorly known. Insulin induces skeletal muscle vasodilation mainly via the endothelium-dependent mechanism and appears to have an important role in normal vascular function. There is increasing amount of evidence that insulin acts as a vasodilatory hormone also in coronary arteries. Insulin enhances myocardial blood flow and decreases coronary vascular resistance in a dose-dependent manner in healthy subjects. Moreover, insulin is able to increase myocardial blood flow also in subjects who are characterized by coronary dysfunction such as subjects with obesity, type 1 diabetes and coronary artery disease. However, vasodilatory effect of insulin may be blunted in these patients. Since already very small increase in myocardial blood flow can reduce significantly myocardial ischemia, these vasodilatory actions of insulin in coronary arteries might partly contribute to beneficial effects of GIK therapy. On the other hand, in contrast to these acute beneficial effect of insulin, epidemiological studies have indentified chronic hyperinsulinemia, a common feature in subjects with insulin resistance to glucose uptake, as an independent risk factor for coronary artery disease. The present article review the physiological and pathophysiological role of insulin in cardiac vasculature and its clinical importance during myocardial ischemia and development of coronary artery disease.
Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD
Authors: Ekim Z. Taskiran, Emine Korkmaz, Safak Gucer, Can Kosukcu, Figen Kaymaz, Cansu Koyunlar, Elizabeth C. Bryda, Moumita Chaki, Dongmei Lu, Komal Vadnagara, Cengiz Candan, Rezan Topaloglu, Franz Schaefer, Massimo Attanasio, Carsten Bergmann, Fatih Ozaltin
Journal: Journal of the American Society of Nephrology (2014)

Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active β-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.
Gene‐centric approach identifies new and known loci for <scp>F</scp>VIII activity and <scp>VWF</scp> antigen levels in <scp>E</scp>uropean <scp>A</scp>mericans and <scp>A</scp>frican <scp>A</scp>mericans
Authors: Weihong Tang, Mary Cushman, David Green, Stephen S. Rich, Leslie A. Lange, Qiong Yang, Russell P. Tracy, Geoffrey H. Tofler, Saonli Basu, James G. Wilson, Brendan J. Keating, Lu‐Chen Weng, Herman A. Taylor, David R. Jacobs, Joseph A. Delaney, Cameron D. Palmer, Taylor Young, James S. Pankow, Christopher J. O'Donnell, Nicholas L. Smith, Alexander P. Reiner, Aaron R. Folsom
Journal: American Journal of Hematology (2015)

Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII :C) and VWF antigen (VWF :Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII :C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII :C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, Ile581Thr, P = 5.10 × 10(-7) in EAs and P = 3.88 × 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg,P = 6.30 × 10(-9) in EAs and P = 2.98 × 10(-2) in AAs. Significant associations for FVIII :C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P = 8.02 × 10(-10) ), with VWF rs1800380 in AAs (P = 5.62 × 10(-11) ), and with MAT1A rs2236568 in AAs (P51.69 × 10(-6) ). We replicated previously reported associations of FVIII :C and VWF :Ag with the ABO blood group, VWF rs1063856(Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII :C and VWF :Ag in both EAs and AAs.
Clinical determinants of incremental shuttle walk test in bronchiectasis
Authors: Sulenur Subasi, Deniz Inal-Ince, Ebru Calik, Naciye Vardar-Yagli, Melda Saglam, Filiz Erdem, Hulya Arikan, Lutfi Coplu
Journal: European Respiratory Journal (2013)

Aim:  The purpose of this study was to investigate the clinical determinants of incremental shuttle walk test (ISWT) in adult patients with bronchiectasis.   Methods:  Thirty two adult bronchiectasis patients aged 18-72 years (23 females, 9 males) participated in the study. Subjects’ demographics and physical characteristics were recorded. Pulmonary function test was performed. MIP and MEP was measured using a mouth pressure device. Dyspnea was assessed using modified Medical Research Council Dyspnea Scale (MMRC). Hand grip strength using a hand held dynamometer and exercise capacity using incremental shuttle walk test (ISWT) were evaluated. Heart rate, modified Borg score for dyspnea and fatigue perception were recorded before and after the ISWT. Quality of life was determined using St George Respiratory Questionnaire (SGRQ).   Results:  Patients reached 24-79% (mean=53.58±13.36%) of predicted ISWT. The ISWT distance was significantly related with age (r=-0.415 p=0.018), BMI (r=-0.419 p=0.019), gender (r= 0.453 p=0.009), FEV 1  (r=0.694 p=0.000), FVC (r=0.518 p=0.003), MIP (r=0.418, p=0.017), MMRC (r=-0.452 p=0.009), handgrip strength (r=0.414 p=0.019), maximal heart rate reached during exercise (r=0.412 p=0.019), and SGRQ total score (r=-0.490, p=0.004). The FEV 1 , maximal heart rate reached during exercise, and SGRQ total explained 72% of the variance in ISWT distance in patient with bronchiectasis (r=0.847, r 2 =0.718, F (1-27) =8.232, p=0.08).   Conclusion:  Multiple regression analysis indicated that level of airway obstruction, maximal heart rate reached during exercise, and SGRQ score were identified as independent predictors of the ISWT, explaining 72% of variance.