tbuckley/cabot-search huggingface dataset:
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Authors: Carlos Cruchaga, John S.K. Kauwe, Oscar Harari, Sheng Chih Jin, Yefei Cai, Celeste M. Karch, Bruno A. Benitez, Amanda T. Jeng, Tara Skorupa, David Carrell, Sarah Bertelsen, Matthew Bailey, David McKean, Joshua M. Shulman, Philip L. De Jager, Lori Chibnik, David A. Bennett, Steve E. Arnold, Denise Harold, Rebecca Sims, Amy Gerrish, Julie Williams, Vivianna M. Van Deerlin, Virginia M.-Y. Lee, Leslie M. Shaw, John Q. Trojanowski, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak-Vance, Lindsay A. Farrer, Gerard D. Schellenberg, Elaine R. Peskind, Douglas Galasko, Anne M. Fagan, David M. Holtzman, John C. Morris, Alison M. Goate
Journal: Neuron (2013)
Myocardial perfusion imaging with a novel selective A2a adenosine receptor agonist (CVT-3146): Important differences in radiotracer behavior
Authors: Farid Jadbabaie, David F. Meoli, Brian N. Bourke, Kailasnath Purushothaman, Lori Brown, Luiz Belardinelli, Albert J. Sinusas
Journal: Journal of the American College of Cardiology (2003)
The effect of streptozotocin-induced diabetes in rats on cardiac contractile proteins.
Authors: A Malhotra, S Penpargkul, F S Fein, E H Sonnenblick, J Scheuer
Journal: Circulation Research (1981)

In order to determine whether diabetic cardiomyopathy in rats is associated with altered contractile proteins, male and female rats were made diabetic with intravenous streptozotocin (STZ). Calcium ATPase activity of cardiac actomyosin was significantly decreased after 1 week of diabetes and was depressed by 60% by 2 weeks. Rats pretreated with 3-O-methyl glucose to prevent the hyperglycemia caused by STZ had normal Ca2+-actomyosin ATPase activities, and non-diabetic rats whose food was restricted to keep their body and heart weights similar to those found in diabetic animals had only a slight fall in actomyosin ATPase activity. Ca2+-ATPase and actin-activated ATPase activities of pure myosin were similarly depressed in preparations from hearts of diabetic animals. Sodium dodecylsulfate gel electrophoresis and isoelectric focusing failed to reveal differences in the patterns of contractile proteins or light subunits between diabetics and controls, but pyrophosphate gels showed a shift in the myosin pattern. Because of depressed circulating thyroid hormone levels in diabetic animals, cardiac contractile proteins were also studied in preparations from thyroidectomized rats. Calcium activities of actomyosin and myosin ATPase were lower than values found in hearts of diabetic rats. When diabetic animals were kept euthyroid with thyroid replacement, actomyosin ATPase activity was still depressed. Thus STZ diabetes causes a significant decrease in cardiac contractile protein ATPase activity. This may be related to altered proportions of myosin isoenzymes.
Health Education's Contributions to Public Health in the Twentieth Century: A Glimpse Through Health Promotion's Rear-View Mirror
Authors: L. W. Green
Journal: Annual Review of Public Health (1999)

▪ Abstract A lesson of the first half of the century was that growth and technological development brought new health problems and challenges in their wake, many of which were to prove more intractable to technological fixes than the ones that had been so dramatically fixed before. Massive expansions of resources in support of the extension of these medical fixes resulted in an escalation of costs that had to be reigned in by breaking from the resource-based planning cycle that had prevailed through two eras of expansion. The 1970s ushered in an era of cost containment as the central theme of new policies. They included provisions for health promotion that sought to find new handles on the intractable social and behavioral aspects of the demand for health care resources, especially through primary prevention and building of capacity for community, family, and individual self-management of health problems and programs. Lessons from this era for public health in the next century are considered.
Patient Selection for Permanent Cardiac Pacing
Authors: J. HAYDEN HOLLINGSWORTH
Journal: Annals of Internal Medicine (1969)

Selection of patients with complete heart block for permanent artificial pacing requires an estimate of the risk of death from heart block in untreated, "minimally symptomatic" patients with block. Of 26 such patients who were not given pacemakers at their initial evaluation, 12 remain minimally symptomatic after an average of 3 years after consideration for pacing. Nine patients subsequently developed symptoms, at which time artificial pacing was provided uneventfully. Five died suddenly and unexpectedly of apparent cardiac arrhythmia. The five patients who died had shown some premonitory symptoms and variation in ventricular activation focus to a greater extent than those 12 who had survived without pacemakers. During the same time 33 patients received artificial pacing because of recurrent syncope or equivalent symptoms of circulatory failure. Of this group there were no operative deaths, three patients died later of unrelated disease with normal pulse rates, and two died with probable rhythm disturbance. This experience indicates that, while most patients with atrioventricular (AV) block provide sufficient symptomatic warning to permit pacing when needed, the risk of sudden death even in the minimally symptomatic patient is considerable, and the risk of artificial pacing has been less. Any patient who has persistent or recurrent episodes of high degrees of AV block, if accompanied by any related symptoms or spontaneous ventricular irritability, should now receive a permanent, artificial pacemaker.
Activation of nitric oxide synthase by ischaemia in the perfused heart
Authors: C Depré
Journal: Cardiovascular Research (1997)

Objective: Recent data have indicated that the activity of nitric oxide synthase (NO synthase), the enzyme producing NO from L-arginine, could be modified by ischaemia. The aim of the present work was therefore to study whether ischaemia activated NO synthase. Methods: NO synthase activity was measured by the conversion of radioactive arginine into citrulline in extracts of isolated perfused rabbit hearts submitted to low-flow ischaemia and reperfusion. Results: When measured in heart homogenates, NO synthase activity was significantly increased during ischaemia. This activation was already detectable after 5 min of ischaemia and was maintained during the whole ischaemic period. After cell fractionation, NO synthase was recovered in cytosolic and membrane fractions. The increase in NO synthase activity by ischaemia was related to an activation of the cytosolic activity, while the membrane-bound NO synthase activity remained constant. Conclusion: NO synthase activity in the heart is rapidly stimulated by ischaemia and this stimulation is maintained during the whole ischaemic episode. This activation is found only in the cytosolic fraction, whereas the particulate activity is not affected by ischaemia.
Efficacy and Costs of Two Forms of Stress Management Training for Cancer Patients Undergoing Chemotherapy
Authors: Paul B. Jacobsen, Cathy D. Meade, Kevin D. Stein, Thomas N. Chirikos, Brent J. Small, John C. Ruckdeschel
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Professionally administered psychosocial interventions have been shown to improve the quality of life of cancer patients undergoing chemotherapy. The present study sought to improve access to psychosocial interventions during chemotherapy treatment by evaluating the efficacy and costs of a patient self-administered form of stress management training that requires limited professional time or experience to deliver. PATIENTS AND METHODS: Four hundred eleven patients about to start chemotherapy were randomly assigned to receive usual psychosocial care only, a professionally administered form of stress management training, or a patient self-administered form of stress management training. Quality-of-life assessments were conducted before randomization and before the second, third, and fourth treatment cycles. Intervention costs were estimated from both payer and societal perspectives. RESULTS: Compared with patients who received usual care only, patients receiving the self-administered intervention reported significantly (P ≤ .05) better physical functioning, greater vitality, fewer role limitations because of emotional problems, and better mental health. In contrast, patients who received the professionally administered intervention fared no better in terms of quality of life than patients receiving usual care only. Costs of the self-administered intervention were estimated to be 66% (from a payer perspective) to 68% (from a societal perspective) less than the average costs of professionally administered psychosocial interventions for patients starting chemotherapy. CONCLUSION: Evidence regarding the efficacy and favorable costs of self-administered stress management training suggests that this intervention has the potential to greatly improve patient access to psychosocial intervention during chemotherapy treatment.
Prevalence, Characteristics, and Outcomes of Patients Presenting With Cardiogenic Unilateral Pulmonary Edema
Authors: David Attias, Nicolas Mansencal, Bertran Auvert, Antoine Vieillard-Baron, Aurélie Delos, Pascal Lacombe, Roland N'Guetta, François Jardin, Olivier Dubourg
Journal: Circulation (2010)

Background— Cardiogenic unilateral pulmonary edema (UPE) is a rare entity, frequently leading to initial misdiagnosis. We sought to assess the prevalence of UPE and to determine its impact on prognosis compared with bilateral pulmonary edema. Methods and Results— We studied the characteristics and outcomes of patients admitted to our institution for cardiogenic pulmonary edema during an 8-year period. The study population included 869 consecutive patients. The prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%). In patients with UPE, blood pressure was significantly lower ( P ≤0.01), whereas noninvasive or invasive ventilation and catecholamines were used more frequently ( P =0.0004 and P &lt;0.0001, respectively). The prevalence of severe mitral regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%, respectively ( P &lt;0.0001). In patients with UPE, use of antibiotic therapy and delay in treatment were significantly higher ( P &lt;0.0001 and P =0.003, respectively). In-hospital mortality was 9%: 39% for UPE versus 8% for bilateral pulmonary edema (odds ratio, 6.9; 95% confidence interval, 2.6 to 18; P &lt;0.001). In multivariate analysis, unilateral location of pulmonary edema was independently related to death whatever the model used (adjusted odds ratio, 6.5; 95% confidence interval, 1.3 to 32; P =0.021 for model A; and adjusted odds ratio, 6.8; 95% confidence interval, 1.1 to 41; P =0.037 for model B). Conclusions— Unilateral pulmonary edema represented 2.1% of cardiogenic pulmonary edema in our study, usually appeared as an opacity involving the right lung, and was always associated with severe mitral regurgitation. Unilateral pulmonary edema is related to an independent increased risk of mortality and should be promptly recognized to avoid delays in treatment.
Muramyl peptides. Variation of somnogenic activity with structure.
Authors: J M Krueger, J Walter, M L Karnovsky, L Chedid, J P Choay, P Lefrancier, E Lederer
Journal: The Journal of Experimental Medicine (1984)

Sleep-promoting activities of muramyl dipeptide (MDP) (NAc-Mur-L-ala-D-isogln) and the naturally occurring muramyl peptide(s), factor S, have recently been demonstrated. We now have amplified our understanding of structural requirements for somnogenic activity. The effects of several analogs of MDP on rabbit slow-wave sleep are presented and these results are compared to the dose-response relationship for MDP. Some tentative conclusions as to structural requirements for somnogenic activity are presented; most notably, amidation of the free gamma-carboxyl of MDP and several of its analogs resulted in the loss of somnogenic activity. MDP also can induce febrile and immunostimulatory responses. In the present paper, we show that some analogs possess immunostimulatory and pyrogenic activity but not somnogenic activity, thus suggesting that these biological activities of muramyl peptides may, in part, be mediated by separate mechanisms.
Gender difference in rat aorta vasodilation after acute exposure to high glucose: Involvement of protein kinase C β and superoxide but not of Rho Kinase
Authors: A GOEL, Y ZHANG, L ANDERSON, R RAHIMIAN
Journal: Cardiovascular Research (2007)

Objectives Several reports suggest that acute hyperglycemia affects male and female vascular beds differently. However, little is known about the interactions between hyperglycemia and gender in the vasculature. The objectives of our study were to investigate if there is a gender-based difference in the relaxation response of rat aorta after acute exposure to high glucose concentration, and the potential role of protein kinase C-beta (PKCβ), superoxide, and Rho kinase in the gender-specific effect of acute high glucose on the relaxation response.
Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure
Authors: S Currie
Journal: Cardiovascular Research (1999)

Objectives: To assess the phosphorylation of myocardial phospholamban (PLB) and quantify protein levels of PLB and sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in a rabbit model of heart failure. Furthermore, to correlate these parameters with the rate of Ca2+ uptake into sarcoplasmic reticulum (SR) vesicles. Methods: Heart failure in the rabbit was indicated by the pronounced ventricular contractile dysfunction accompanied by post-mortem evidence of lung and liver congestion 8 weeks after a coronary artery ligation procedure. Phosphorylation of PLB was measured by reduced mobility of the phosphorylated forms on Tris–glycine gels. Phosphoserine and phosphothreonine-specific antibodies against PLB were used to determine the phosphorylated residues. Immunoblotting combined with densitometry was used to assess PLB and SERCA 2 levels. Finally, oxalate-supported Ca2+ uptake into SR vesicles was studied using the fluorescent indicator Fura-2. Results: The phosphorylation state of PLB was significantly higher in myocardium isolated from left ventricles of heart failure rabbits (8.3±0.42 P-PLB) when compared with sham-operated animals (4.0±1.7 P-PLB). The kinase activity associated with SR vesicles isolated from animals with heart failure was a factor of 1.58±0.21-times higher than sham hearts, as assessed by the initial rate of phosphorylation of PLB. This higher kinase activity observed in heart failure was not completely abolished by inhibitors of either A-kinase, C-kinase or Ca2+/calmodulin-dependent protein kinase (CaM-kinase). Abundance of SERCA in heart failure myocardial homogenates was significantly less than sham values (0.68±0.11 vs. 1.74±0.27) as was PLB (0.41±0.08 vs. 0.69±0.13), similar reductions were seen in vesicle preparations. The rate constant of Ca2+ uptake into the isolated SR vesicles was lower in preparations from heart failure myocardium than from sham myocardium (2.50±0.23 ms vs. 4.43±0.3 ms). Conclusions: The higher level of phosphorylation of PLB observed in the left ventricle of rabbits with heart failure is associated with a higher intrinsic kinase activity of the SR. However, the abundance of both of SERCA 2 and PLB proteins are lower in heart failure. The net effect of these changes appears to be a reduced rate of Ca2+ uptake by the SR in heart failure.
Electrophysiological Effects of 4-Hydroxynonenal, an Aldehydic Product of Lipid Peroxidation, on Isolated Rat Ventricular Myocytes
Authors: Aruni Bhatnagar
Journal: Circulation Research (1995)

Aldehydic products of lipid peroxidation, such as 4-hydroxynonenal (4-HNE), have been implicated in the etiology of pathological changes under oxidative stress. To identify the mechanism by which 4-HNE alters cellular excitability, its effects on isolated rat ventricular myocytes were studied. Superfusion with 100 to 880 mumol/L 4-HNE led to a time- and concentration-dependent rigor shortening of myocytes. A reduction in [Ca2+]o and inhibition of transsarcolemmal Ca2+ transport by 1 mmol/L La3+ did not affect either the magnitude or the time course of 4-HNE-induced myocyte rigor. Superfusion of myocytes with 400 mumol/L 4-HNE led to an increase in the action potential duration, progressive depolarization of the resting membrane potential, and an increase in the input resistance (Rin) of the myocyte (phase I), followed by a loss of electrical excitability. Continued superfusion with 4-HNE resulted in membrane hyperpolarization and a prominent decrease in the Rin (phase II). The decrease in Rin coincided with myocyte rigor. In whole-cell voltage-clamp experiments, superfusion with 4-HNE inhibited current through the inward rectifier K+ channel (IK1). 4-HNE had no effect on either the magnitude or the rate of "rundown" of L-type Ca2+ currents. Exposure to 4-HNE led to an increase in the magnitude of the fast inward Na+ current (INa). The voltage dependence of the steady state parameters for activation and inactivation of INa shifted to more positive potentials, with a resultant increase in the window current. 4-HNE-induced myocyte rigor was accompanied by a large increase in time-independent currents that displayed linear dependence on the membrane potential and were inhibited by glibenclamide, suggesting activation of the ATP-sensitive K+ channel. Steady state currents recorded in Cs(+)-containing Ringer's solution with La3+ and tetrodotoxin and Cs(+)-containing internal solution (leak currents) were not affected by 4-HNE. Superfusion with 4-HNE resulted in a significant decrease in the cellular concentration of nonprotein thiols and a severe decrease in [ATP]i. The energy charge of the myocytes fell from 0.9 to 0.3. These observations indicate that 4-HNE-induced membrane depolarization may be due to an inhibition of IK1. Changes in voltage dependence of INa, inhibition of IK1, and membrane depolarization appear to contribute to the prolongation of the action potential, observed during phase I. Depletion of [ATP]i may be responsible for changes observed during phase II, ie, activation of the ATP-sensitive K+ channels, membrane hyperpolarization, decrease in Rin, and rigor shortening of the myocytes. These results suggest that stable products of lipid peroxidation, such as 4-HNE, are proarrhythmic and may contribute to the cytotoxic effects of oxidative stress.
Potential Additional Effect of Omentectomy on Metabolic Syndrome, Acute-Phase Reactants, and Inflammatory Mediators in Grade III Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass
Authors: Miguel F. Herrera, Juan Pablo Pantoja, David Velázquez-Fernández, Javier Cabiedes, Carlos Aguilar-Salinas, Eduardo García-García, Alfredo Rivas, Christian Villeda, Diego F. Hernández-Ramírez, Andrea Dávila, Aarón Zaraín
Journal: Diabetes Care (2010)

To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB).Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups.Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute-phase reactants, and inflammatory mediators.Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.
A novel model of CCl4-induced cirrhosis with ascites in the mouse
Authors: Marco Domenicali, Paolo Caraceni, Ferdinando Giannone, Maurizio Baldassarre, Giovanna Lucchetti, Carmelo Quarta, Corrado Patti, Lucia Catani, Cristina Nanni, Roberto M. Lemoli, Mauro Bernardi
Journal: Journal of Hepatology (2009)
Functional Role and Prognostic Significance of CD157 in Ovarian Carcinoma
Authors: Erika Ortolan, Riccardo Arisio, Simona Morone, Paola Bovino, Nicola Lo-Buono, Giulia Nacci, Rossella Parrotta, Dionyssios Katsaros, Ida Rapa, Giuseppe Migliaretti, Enza Ferrero, Marco Volante, Ada Funaro
Journal: JNCI Journal of the National Cancer Institute (2010)

CD157, an ADP-ribosyl cyclase-related cell surface molecule, regulates leukocyte diapedesis during inflammation. Because CD157 is expressed in mesothelial cells and diapedesis resembles tumor cell migration, we investigated the role of CD157 in ovarian carcinoma.We assayed surgically obtained ovarian cancer and mesothelial cells and both native and engineered ovarian cancer cell lines for CD157 expression using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and for adhesion to extracellular matrices, migration, and invasion using cell-based assays. We investigated invasion of human peritoneal mesothelial cells by serous ovarian cancer cells with a three-dimensional coculture model. Experiments were performed with or without CD157-blocking antibodies. CD157 expression in tissue sections from ovarian cancer patients (n = 88) was examined by immunohistochemistry, quantified by histological score (H score), and categorized as at or above or below the median value of 60, and compared with clinical parameters. Statistical tests were two-sided.CD157 was expressed by ovarian cancer cells and mesothelium, and it potentiated the adhesion, migration, and invasion of serous ovarian cancer cells through different extracellular matrices. CD157-transfected ovarian cancer cells migrated twice as much as CD157-negative control cells (P = .001). Blockage of CD157 inhibited mesothelial invasion by serous ovarian cancer cells in a three-dimensional model. CD157 was expressed in 82 (93%) of the 88 epithelial ovarian cancer tissue specimens. In serous ovarian cancer, patients with CD157 H scores of 60 or greater had statistically significantly shorter disease-free survival and overall survival than patients with lower CD157 H scores (CD157 H score > or =60 vs <60: median disease-free survival = 18 months, 95% confidence interval [CI] = 5.92 to 30.07 vs unreached, P = .005; CD157 H score > or =60 vs <60: median overall survival = 45 months, 95% CI = 21.21 to 68.79 vs unreached, P = .024). Multivariable Cox regression showed that CD157 is an independent prognostic factor for recurrence (hazard ratio of disease recurrence = 3.01, 95% CI = 1.35 to 6.70, P = .007) and survival (hazard ratio of survival = 3.44, 95% CI = 1.27 to 9.31, P = .015).CD157 plays a pivotal role in the control of ovarian cancer cell migration and peritoneal invasion, and it may be clinically useful as a prognostic tool and therapeutic target.
Series Introduction: The expanding network of redox signaling: new observations, complexities, and perspectives
Authors: Roy J. Soberman
Journal: Journal of Clinical Investigation (2003)

Nonstandard abbreviations used: reactive oxygen species (ROS); hydrogen peroxide (H2O2); hypoxia inducible factor 1 (HIF-1); carboxy-terminal binding protein (CtBP); apoptosis-inducing factor (AIF); apoptosis signal-regulating kinase