tbuckley/cabot-search huggingface dataset:
Abstract 185: Whole Body Periodic Acceleration (pGz) in Mice Increases Antioxidant Enzymes in the Heart
Authors: Arkady Uryash, Jorge Bassuk, Paul Kurlansky, Jose R Lopez-Padrino, Jose A Adams
Journal: Circulation (2012)

BACKGROUND: Mild to moderate exercise produces cardio and neuroprotection. Exercise increases pulsatile shear stress that provide several cytoprotective and signaling substances from muscle and endothelium. Some beneficial effects of exercise on cytoprotection are derived from increased antioxidant capacity. pGz is a passive exercise strategy that moves the body in a sinusoidal head to foot motion, adding pulses to the circulation thereby increasing pulsatile, cyclical shear stress to the endothelium. pGz activates the PI3/Akt eNOS pathway and increases release of eNO and its enzyme (eNOS), and other cytoprotective signaling and substances, and decreases reperfusion injury. Optimum frequency of pGz has been established in our laboratory for various animal species and humans. We tested the hypothesis that repeated exposure to pGz in mice would increase antioxidant enzymes, and determined its time course. METHODS: Acclimated awake mice (n=48) where exposed to shear stress at f ƒ=480 cpm, Gz ± 3mt/sec 2 (pGz) 1 hr daily sessions of 1, 2, and 4 weeks of pGz. Myocardial tissue was harvested prior to pGz (BL) and 24 hrs after the last pGz treatment for proteins via Western Blot analyses: Glutathioneperoxidase-1(GPX1), Superoxide Dismutase -1 (Cu-Zn SOD), Superoxide Dismutase -2 (mitochondrial or Mn-SOD) and Catalase (Cat) , Protein content was normalized to GAPDH. RESULTS:One to four weeks of pGz increased GPX1, Cat and SOD1 from BL levels, whereas SOD2 remained unchanged. 4 weeks of pGz increased GPX1, Cat and SOD1, by 110%, 80% and 240% of basal enzyme levels. (Data= mean ± SEM, Figure † p&lt; 0.01 BL vs. 1,2,4 wks) CONCLUSIONS: One hour daily pGz increases cardiac antioxidant enzymes and may serve as a method to augment endogenous antioxidant capacity, and decrease reperfusion injury.
Measles resurgence in Belgium from January to mid-April 2011: a preliminary report
Authors: M Sabbe, D Hue, V Hutse, P Goubau
Journal: Eurosurveillance (2011)

From 1 January to 14 April 2011, a total of 155 measles cases were notified in Belgium, whereas throughout 2010, there were only 40. Of the 103 cases with known vaccination status, 87% had not been vaccinated with measles-mumps-rubella vaccine. The resurgence of measles is the consequence of insufficient vaccine coverage in previous years. Efforts to communicate the benefits of measles vaccination to the public and to advise health professionals on control measures and outbreak management are ongoing.
Targeting Stat3 in hepatocellular carcinoma with aberrant TGF-b signaling
Authors: aiwu He, Ling Lin, Rupen Amin, Wilma Jogunoori, John Marshall, Michael Zasloff, Lopa Mishra
Journal: Cancer Research (2008)

2377  Hepatocellular Carcinoma (HCC) is the third leading cause of cancer death worldwide, yet there still remain only a few effective therapeutic options for advanced disease. At least 40% of HCCs are clonal and thought to arise from liver progenitor/stem cell transformation, and requiring activation of stem cell renewal factors such as Stat3, Nanog, Oct 3/4. We have found that these HCCs frequently develop in the setting of inactivated TGF-β signaling (Science, 2005, 310(5745):68-71, Oncogene 2007, 26(50):7103-10). The Aims of this study were to expand on our understanding of the intracellular signaling pathways activated in HCC, and to develop new therapeutics targeting HCC-specific signaling pathways. Methods and Results: 1. IL6/Stat3 activity, is markedly increased in 9/10 human HCC tissues and growth of HCC cell lines could be inhibited with the Stat3 inhibitor, NSC 74859. 2. A method was developed to isolate putative HCC progenitor/stem cells, for the purpose of characterizing their response to potential therapeutics. Progenitor/stem cells were isolated from the HCC cell line, Huh7 utilizing antibodies to the stem cell surface marker CD133. We found that CD133+ Huh7 cells differ from CD133- cells with their ability of forming colonies on soft agar with as few as five cells and expression of other stem cell surface markers (Oct4, CD44). 3. These CD133+ cells are more resistant to doxorubicin compared to CD133- cells, consistent with the known resistance of HCC to this agent, yet these CD133+ cells are highly sensitive to Stat3 inhibition. 4. Exposure of CD133+ HCC cells to the Stat3 inhibitor resulted in significant growth suppression, with the most potent effects observed in those lines lacking a functional TGF-β pathway. Conclusion:  Inhibiting IL-6/Stat3, a major signaling pathway in HCC stem cell renewal and proliferation might provide a new approach to the targeted treatment of certain forms of HCC.
A controlled trial of brief psychotherapy and mutual-help group treatment of conjugal bereavement
Authors: C R Marmar, M J Horowitz, D S Weiss, N R Wilner, N B Kaltreider
Journal: American Journal of Psychiatry (1988)

Sixty-one women who sought treatment for unresolved grief reactions 4 months to 3 years after the death of their husbands were randomly assigned to either brief dynamic psychotherapy with experienced clinicians or mutual-help group treatment led by nonclinicians. Women in both groups experienced a reduction in stress-specific and general symptoms as well as improvement in social and work functioning. Women in the brief psychotherapy group showed a greater decline in one measure of general symptoms, and there was greater attrition in the group treatment condition. When two subgroups who had completed the majority of sessions were compared, treatments were found to be equally effective.
Ingestion of mouthwash by children
Authors: T. Wade, A. Gammon, M. Kelly
Journal: BMJ (1999)

Editor—A 3 year old boy was found collapsed and unresponsive at home by his mother. While waiting for the ambulance his mother discovered that a bottle of mouthwash was not in its usual place and she feared that her son had ingested some.

On arrival at the accident and emergency department, the child was comatose (Glasgow coma scale score 3) but breathing on his own, and his oxygen saturation was good. He was hypothermic (core temperature 34.2°C), and capillary refill time was 3 seconds. A minty odour was detectable on his breath.

Initial blood glucose estimation was 2.1 mmol/l, and he received 3 ml/kg of 10% dextrose and 20 ml/kg of colloid. At 10 minutes a repeat blood glucose of 2.2 mmol/l was followed by administration of 2 ml/kg of 20% dextrose. Twenty minutes after arrival his blood glucose was 8.7 mmol/l, his coma score was 13, and capillary refill time was 3 seconds. He received another bolus of 20 ml/kg of colloid, and by 30 minutes after arrival he was awake and alert.

Initial arterial blood gas measurements indicated a marked metabolic acidosis (pH 7.19, base excess 16 mmol/l). His initial serum alcohol concentration was 101 mg/dl. By 10 hours after admission his blood glucose was stable and the acidosis had resolved. He made a full recovery.

The mouthwash that he had ingested was a supermarket “extra strength” own brand which contains 37% alcohol. It is supplied in a 500 ml container without a child proof cap. The child’s parents were unaware that there was any danger associated with the ingestion of mouthwash.

In a recent survey of poisonings in children under age 6, 12.5% were found to be due to “cosmetics, personal-care products or alcohol-containing products” including mouthwashes.1 Of the poisonings involving products containing alcohol, 97% were not beverages but other substances, which included perfumes and mouthwash.

Mouthwashes, unlike perfumes, are usually highly palatable, brightly coloured, and readily available to young children. Manufacturers are not required to use child proof containers or specify the alcohol content.

A review of the literature identified seven other case reports worldwide of acute coma secondary to mouthwash ingestion in children. Of these, five had documented evidence of hypoglycaemia before treatment. Two children died despite resuscitation efforts.

There have been calls for more stringent safety controls for mouthwashes since the first case report 19 years ago but no legislative action has been taken. Child proof containers and larger, more specific warning labels are urgently needed and could prevent the deaths of children.
Leukotriene modifiers in the treatment of asthma
Authors: A. Sampson, S. Holgate
Journal: BMJ (1998)

Leukotriene modifiers are an entirely new class of asthma treatment, which have entered clinical practice in 1996-7 in several countries including Britain, Japan, and the United States. Their development is an example of rational drug design following the elucidation of leukotriene structures in 1979-80 and the subsequent confirmation of their pathophysiological role as inflammatory mediators in asthma.1

There are two types of leukotriene modifier: leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.2 Both are used to block the bronchoconstrictor and pro-inflammatory activity of cysteinyl leukotrienes within the asthmatic airway. Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) were originally identified as long lasting smooth muscle spasmogens and collectively termed “slow reacting substance of anaphylaxis” (SRS-A). They are now known to be metabolites of arachidonic acid formed by the 5-lipoxygenase pathway1 and are produced almost exclusively by inflammatory leucocytes, especially mast cells, basophils, and eosinophils. The leukotriene receptor antagonists block the activity of cysteinyl leukotrienes at their receptors ( CysLT  1 ) on bronchial smooth muscle and elsewhere, while the leukotriene synthesis inhibitors block the synthesis of all leukotrienes by interrupting the 5-lipoxygenase pathway.2

Cysteinyl leukotrienes are among …
Abstract 1522: Anxiety with Depression is Associated with Increased Platelet Reactivity In Stable Acute Coronary Syndrome Patients
Authors: Manuel Paz-Yepes, Mohammad U Zafar, Daichi Shimbo, Gemma Vilahur, Karina Davidson, Valentin Fuster, Juan J Badimon
Journal: Circulation (2007)

INTRODUCTION: Platelets play a central role in the pathophysiology of acute coronary syndromes. Studies show psychological factors (depression and more recently anxiety) enhance the risk of recurre...
Virus, bacteria and lipopolysaccharide increase basophil cell response to histamine releasing stimulators and calcium
Authors: P. Clementsen, K. S. Kristensen, S. Norn
Journal: Allergy (1991)

Histamine release from human basophil leukocytes from allergic patients or controls was induced by specific antigens, anti‐IgE or calcium ionophore A23187, Influenza A virus, S. aureus and lipopolysaccharide from S. typhimurium increased the maximum release of histamine and caused a shift lo the left of the dose‐response curves showing increased cell sensitivity and lowering of the threshold to these stimuli. The mechanism of action was elucidated by examining the mediator release as a function of increasing extracellular concentration of calcium, in these experiments the dose‐response curves were changed by the microorganisms and lipopolysaccharide as before. This indicates that the microorganisms and lipopolysaccharide change the basophil cell response to IgE‐dependent and non‐immunological stimuli by causing a change in the subcellular handling of calcium.
Abstract 9600: Abnormal Lipoprotein Metabolism Other Than LDL Fraction in Familial Hypercholesterolemia: Serial analysis using Ultracentrifugation Method
Authors: Hayato Tada, Masa-aki Kawashiri, Akihiko Hodatsu, Chiaki Nakanishi, Tetsuo Konno, Kenji Sakata, Tsuyoshi Yoshimuta, Kenshi Hayashi, Atsushi Nohara, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
Journal: Circulation (2014)

Background: It is well known that familial hypercholesterolemia (FH) is a common inherited disorder that could cause marked elevation of plasma LDL-C level. However, few data exists regarding the clinical impact of plasma levels of VLDL-C and IDL-C as well as the composition of each lipoprotein fraction in FH. Thus, we assessed the hypothesis that the abnormality in LDLR modulates the quality as well as the quantity of lipoprotein other than LDL fraction. Methods: We investigated the plasma lipoprotein by ultracentrifugation method about 146 controls (mean age=61.4±17.1yr, mean LDL-C=92.7±61.2mg/dl), 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0yr, mean LDL-C=225.1±61.2mg/dl), and 16 homozygous mutation-determined FH subjects (mean age=26.9±17.1yr, mean LDL-C=428.6±86.1mg/dl). In addition, we evaluated the composition of each lipoprotein fraction by calculated cholesterol ester (CE) / triglyceride (TG) ratio. Results: As shown in the figure, the differences of the levels of TC and LDL-C between these 3 groups as well as those of VLDL-C (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively) and IDL-C (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively) were statistically significant. Moreover, the ratios of CE/TG of each lipoprotein fraction significantly increased in heterozygous FH and homozygous FH group, compared with that of controls, suggesting that the abnormality in LDLR modulate the quality as well as the quantity of each lipoprotein fraction. Conclusions: Our results indicate that LDLR participate not only in metabolism of LDL fraction but also in that of VLDL and IDL fractions. Larger amounts of VLDL-C and IDL-C with worse quality should also be additive risk factor in FH subjects.
Abstract 3461: Inhibition of the p38 MAP Kinase in Vivo Improves Number and Functional Activity of Progenitor Cells and Reduces Atherosclerotic Disease Progression
Authors: Florian Seeger, Daniel Sedding, Alexander C Langheinrich, Tina Rasper, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2008)

Initial trials suggest that bone marrow-derived mononuclear cells (BMC) and ex vivo expanded endothelial progenitor cells (EPC) augment neovascularisation in patients after myocardial infarction. However, patients with cardiovascular risk factors show reduced number and impaired functional activity of EPC and increased activity of the p38 MAP kinase. Therefore, we examined the effect of p38 MAP kinase inhibition on progenitor cells in an in vivo model of metabolic syndrome and atherosclerosis. Consistent with the impairment of EPC by risk factors for coronary artery disease in humans, Lepr db mice exhibited a significantly lower number of EPC (sca-1 + /flk-1 + cells) and an increased number of inflammatory cells (Gr1 + /CD45 + cells) compared to their wild type littermates (0.05±0.07% vs. 1.6±1.1%, and 48.2±11% vs. 23.4±5.9%, respectively). Treatment of Lepr db mice with the p38 inhibitor SB203580 significantly increased the number of sca-1 + /flk-1 + cells (29±7 -fold increase) and lowered the number of GR1 + /CD45 + cells (69±11% of Lepr db mice). Moreover, both, reduced EPC colony forming activity (60±6 % of wt), and impaired BMC invasion capacity (58±13% of wt) were significantly improved in Lepr db mice by p38 inhibition. Finally, treatment of ApoE −/− mice with the SB203580 for 4 months reduced atheromatous lesion size by 51±3% (p&lt;0.05). This study provides first evidence that p38 MAP kinase inhibition with SB203580 improves the impaired progenitor cell number and functional activity in an animal model of metabolic syndrome. Improvement of progenitor cell function is associated with reduction of atheroscle-rotic disease progression in ApoE −/− mice.
Abstract 12680: Efficacy and Safety of Edoxaban Compared With Warfarin in Patients With Atrial Fibrillation and Heart Failure: Insights From Engage-AF TIMI 48
Authors: Giulia Magnani, Robert P Giugliano, Christian T Ruff, Sabina A Murphy, Francesco Nordio, Howard Rutman, Valentin Curt, Minggao ShI, Michele Mercuri, Eugene Braunwald, Elliott M Antman
Journal: Circulation (2014)

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) have emerged as the two epidemics of cardiovascular (CV) disease. The prevalence of AF increases with the severity of HF and contributes to HF disability. Among patients treated with vitamin K antagonists (VKAs), symptomatic HF is an independent risk factor for lower time in therapeutic range (TTR), which reduces the efficacy and safety of VKAs. METHODS: In the ENGAGE AF-TIMI 48 trial, both once-daily regimens of the direct oral factor Xa inhibitor edoxaban [high (HDE) and low dose (LDE)], were non inferior to warfarin (W) for prevention of stroke and systemic embolic events (SEE) in patients with AF and were associated with lower rates of bleeding. We evaluated the safety and the efficacy of edoxaban compared with W in patients with HF presenting with different severity of functional limitation (NYHA class). RESULTS: Among 21,105 patients enrolled 8,981(43%) had no history of HF, 9,489 (45%) had history of HF and a NYHA class I-II, whereas 2,635 (13%) had symptomatic HF with NYHA class III-IV. Patients with more severe HF symptoms had higher rates of stroke SEE, CV death and CV hospitalization (p&lt;0.0005 for all) and among those treated with W we observed a lower mean TTR (62.6% vs. 70.0%, p&lt;0.001). Compared with W, the efficacy of both edoxaban doses in reducing stroke or SEE was similar between patients with and without HF (HDE vs. W, p int=0.96; LDE vs. W, p int=0.63, Fig.) and there were no differences between NYHA classes. CV hospitalization was significantly reduced with HDE relative to W, without heterogeneity by different NYHA classes (p int=0.5, Fig.). Both edoxaban regimens reduced consistently major bleeding and intracranial hemorrhage, regardless of HF severity (Fig.). CONCLUSION: The relative efficacy and safety of both edoxaban regimens, compared to well-managed W in AF patients with HF, was consistent irrespective of the severity of functional class.
Abstract 12931: Does Reporting Non-High-Density-Lipoprotein Cholesterol (Non-HDL-C) Levels on Standard Lipid Panel Improve Non-HDL-C Goal Attainment
Authors: Salim S Virani, Supicha Chitwood, Degang Wang, Lechuancy Woodard, Franklin J Zieve, Christie M Ballantyne, Laura A Petersen
Journal: Circulation (2011)

Background: The Adult Treatment Panel (ATP) III guidelines established non-high-density-lipoprotein-cholesterol (non-HDL-C) as a secondary cholesterol treatment target. Non-HDL-C goal attainment remains poor in cardiovascular disease (CVD) patients and approximately 50% of the providers may not be able to calculate non-HDL-C (total cholesterol minus HDL-C). We determined whether simple reporting of non-HDL-C levels on standard lipid panels can improve non-HDL-C goal attainment.

Methods: We identified CVD patients receiving primary care within the Veterans Health Administration using International Classification of Diseases, 9th revision, diagnoses codes or current procedural terminology codes. Facility A (3,994 CVD patients) started reporting non-HDL-C levels on lipid panels beginning 9/9/08. To account for temporal trends in non-HDL-C goal attainment, we matched facility A to facility B of a similar size, patient complexity, and academic mission (4,269 CVD patients) that does not report non-HDL-C levels. Primary outcome was the difference in non-HDL-C levels from baseline to the most recent lipid panel for CVD patients seeking care at these facilities.

Results: Baseline non-HDL-C levels at facilities A and B were 114 mg/dl and 107 mg/dl, respectively. At 2.3 years of follow-up, mean non-HDL-C levels decreased at both facilities, but there was a greater decrease at the facility reporting non-HDL-C (facility A = -11 mg/dl versus facility B = -3 mg/dl, p <0.001). The results remained significant (p <0.001) after adjusting for patient's age, race, illness-burden, history of diabetes, hypertension, medication adherence, number of lipid panels, and number of primary care visits between baseline and follow-up. Greater reductions in non-HDL-C were seen among patients with triglycerides ≥ 200 mg/dl at baseline (-25 mg/dl at facility A versus -16 mg/dl at facility B, p=0.002 in adjusted models)

Conclusion: Direct non-HDL-C reporting could be an important implementation strategy to improve non-HDL-C goal attainment especially if non-HDL-C is retained as a treatment target in ATP IV guidelines. Future work should compare the effectiveness of different methods of improving compliance with cholesterol management guidelines for CVD patients.
Abstract 2135: Decreased Functional Status and Ventricular Function in Fontan Patients With Pacemakers
Authors: Richard Williams, Thomas Travison, Jonathan R Kaltman, Frank Cecchin, Steven Colan, Salim F Idriss, Minmin Lu, Renee Margossian, John H Reed, Eric E Silver, Elizabeth A Stephenson, Victoria L Vetter
Journal: Circulation (2009)

Background: Many Fontan patients (pts) require a pacemaker. Few studies have characterized paced Fontan pts. Purpose: To compare clinical characteristics, functional status and ventricular performa...
Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis
Authors: Chun-Jung Ko, Cheng-Chung Huang, Hsin-Ying Lin, Chun-Pai Juan, Shao-Wei Lan, Hsin-Yi Shyu, Shang-Ru Wu, Pei-Wen Hsiao, Hsiang-Po Huang, Chia-Tung Shun, Ming-Shyue Lee
Journal: Cancer Research (2015)

Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a substrate for TMPRSS2 in mediating this proinvasive action of androgens in prostate cancer. Further, we determined that higher levels of TMPRSS2 expression correlate with higher levels of matriptase activation in prostate cancer tissues. Lastly, we found that the ability of TMPRSS2 to promote prostate cancer tumor growth and metastasis was associated with increased matriptase activation and enhanced degradation of extracellular matrix nidogen-1 and laminin β1 in tumor xenografts. In summary, our results establish that TMPRSS2 promotes the growth, invasion, and metastasis of prostate cancer cells via matriptase activation and extracellular matrix disruption, with implications to target these two proteases as a strategy to treat prostate cancer.
Abstract P297: Repeated Measures of Albuminuria in the Rancho Bernardo Study: 1992-2005
Authors: Simerjot K Jassal, Jaclyn Bergstrom, Joachim Ix, Dena Rifkin, Elizabeth Barrett-Connor
Journal: Circulation (2014)

Albuminuria is an early, non-invasive marker of kidney injury, and an independent, potentially modifiable, risk factor for cardiovascular disease. Between 1992-96, 1764 community-dwelling men and women 31-98 (mean 71) years old were assessed for albuminuria using spot urine albumin/creatinine ratio (ACR). Median (interquartile range) ACR was 12 (7-20) mg/g. ACR was repeated in 1997-99 (n=926; ACR 12 [7-20]), 1999-2002 (n=977; ACR 16 [9-32]) and 2003-05 (n=755; ACR 11 [6-20]) (Figure). In analyses limited to 977 participants with ACR measured at 1992-96 and 1999-2002 visits, mean 6.6 (range 4.5-9.5) years later, median change in ACR was 4 (-1-17) mg/g; ACR doubled or greater in 36%, halved or less in 10%, and was unchanged in 54%. Table shows change in ACR by baseline characteristics. Using logistic regression, only sex was associated with doubling of ACR (vs. less than doubling); OR 1.42 (95% CI 1.08-1.87, p=0.01) for women; age, blood pressure, and diabetes were not; none of these were associated with halving of ACR. Further studies of predictors of albuminuria may inform future interventions to modify albuminuria and mitigate kidney and cardiovascular risk.