tbuckley/cabot-search huggingface dataset:
MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species
Authors: Hajime Morimoto, Masamichi Hirose, Masafumi Takahashi, Masanori Kawaguchi, Hirohiko Ise, Pappachan E. Kolattukudy, Mitsuhiko Yamada, Uichi Ikeda
Journal: Cardiovascular Research (2008)

AimsMonocyte chemoattractant protein-1 (MCP-1: CCL2) has been demonstrated to be involved in the pathophysiology of ischaemic heart disease; however, the precise role of MCP-1 in ischaemia/reperfusion (I/R) injury is controversial. Here, we investigated the role of cardiac MCP-1 expression on left ventricular (LV) dysfunction after global I/R in Langendorff-perfused hearts isolated from transgenic mice expressing the mouse JE-MCP-1 gene under the control of the α-cardiac myosin heavy chain promoter (MHC/MCP-1 mice).
Trends of Diagnosis-Specific Work Disability After Newly Diagnosed Diabetes: A 4-Year Nationwide Prospective Cohort Study
Authors: Marianna Virtanen, Jenni Ervasti, Ellenor Mittendorfer-Rutz, Petter Tinghög, Tea Lallukka, Linnea Kjeldgård, Jaana Pentti, Kristina Alexanderson
Journal: Diabetes Care (2015)

OBJECTIVE We examined trends of diagnosis-specific work disability after newly diagnosed diabetes, comparing individuals with diabetes with those without diabetes, and identified the subgroups with the highest levels of work disability. RESEARCH DESIGN AND METHODS The register data of diabetes medication and in- and outpatient hospital visits were used to identify all recorded new diabetes cases among the population aged 25–59 years in Sweden in 2006 (n = 14,098). Data for a 4-year follow-up of ICD-10 physician-certified sickness absence and disability pension days (2007‒2010) were obtained from the Swedish Social Insurance Agency. Comparisons were made using a random sample of the population without recorded diabetes (n = 39,056). RESULTS The most common causes of work disability were mental and musculoskeletal disorders; diabetes as a reason for disability was rare. Most of the excess work disability among people with diabetes compared with those without diabetes was owing to mental disorders (mean difference adjusted for confounding factors 18.8‒19.8 compensated days/year), musculoskeletal diseases (12.1‒12.8 days/year), circulatory diseases (5.9‒6.5 days/year), diseases of the nervous system (1.8‒2.0 days/year), and injuries (1.0‒1.2 days/year). The disparity in mental disorders first widened and then narrowed, while the difference in other major diagnostic categories was stable over 4 years. The highest rate (45.3 days/year) was found among people who had diabetes, lived alone, and were disabled from work owing to mental disorders. CONCLUSIONS The increased risk of work disability among those with diabetes is largely attributed to comorbid mental, musculoskeletal, and circulatory diseases. It is important to monitor comorbid conditions and take account of socioeconomic disadvantage.
Angiopoietin 1 Is Mitogenic for Cultured Endothelial Cells
Authors: Shigeru Kanda, Yasuyoshi Miyata, Yasushi Mochizuki, Toshifumi Matsuyama, Hiroshi Kanetake
Journal: Cancer Research (2005)

Abstract The angiopoietin (Ang)/Tie2 system is implicated in blood vessel formation and maturation. However, the mitogenic effects of angiopoietins remain to be elucidated. Here, we show that Ang1 is mitogenic for cultured endothelial cells. Ang1 dose-dependently induced the proliferation and increased the labeling index of a murine brain capillary endothelial cell line, IBE cells. Ang1 also increased the labeling index of human umbilical vein endothelial cells (HUVEC). Ang1 up-regulated the expression of cyclin D1 in both of these cells. Ang1 activated mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) in IBE cells and HUVECs. Activated PI3K was associated with c-Fes protein tyrosine kinase in these cells, but not with Tie2. p70 S6 kinase (p70 S6K) was activated by Ang1-treatment, although this activation was blocked by a PI3K inhibitor, LY294002. Simultaneous treatment of cells with PD98059 (MAPK/extracellular regulated kinase kinase inhibitor) and rapamycin (mTOR inhibitor) completely blocked Ang1-induced mitogenic activity for IBE cells and HUVECs. Although Ang2 at high concentration weakly activated Tie2 and p70 S6K, it failed to activate Ras and MAPK, or to induce cell proliferation. Taken together, these findings indicate that Ang1 exerts mitogenic activity on endothelial cells, which requires activation of both MAPK and p70 S6K.
Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Authors: Cesare Hassan, Enrique Quintero, Jean-Marc Dumonceau, Jaroslaw Regula, Catarina Brandão, Stanislas Chaussade, Evelien Dekker, Mario Dinis-Ribeiro, Monika Ferlitsch, Antonio Gimeno-García, Yark Hazewinkel, Rodrigo Jover, Mette Kalager, Magnus Loberg, Christian Pox, Bjorn Rembacken, David Lieberman
Journal: Endoscopy (2013)

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. <b>Main recommendations:</b> The following recommendations for post-polypectomy endoscopic surveillance should be applied only after a high quality baseline colonoscopy with complete removal of all detected neoplastic lesions. <b>1</b> In the low risk group (patients with 1 – 2 tubular adenomas < 10 mm with low grade dysplasia), the ESGE recommends participation in existing national screening programmes 10 years after the index colonoscopy. If no screening programme is available, repetition of colonoscopy 10 years after the index colonoscopy is recommended (strong recommendation, moderate quality evidence). <b>2 </b>In the high risk group (patients with adenomas with villous histology or high grade dysplasia or ≥10 mm in size, or ≥ 3 adenomas), the ESGE recommends surveillance colonoscopy 3 years after the index colonoscopy (strong recommendation, moderate quality evidence). Patients with 10 or more adenomas should be referred for genetic counselling (strong recommendation, moderate quality evidence). <b>3</b> In the high risk group, if no high risk adenomas are detected at the first surveillance examination, the ESGE suggests a 5-year interval before a second surveillance colonoscopy (weak recommendation, low quality evidence). If high risk adenomas are detected at first or subsequent surveillance examinations, a 3-year repetition of surveillance colonoscopy is recommended (strong recommendation, low quality evidence). <b>4 </b>The ESGE recommends that patients with serrated polyps < 10 mm in size with no dysplasia should be classified as low risk (weak recommendation, low quality evidence). The ESGE suggests that patients with large serrated polyps (≥ 10 mm) or those with dysplasia should be classified as high risk (weak recommendation, low quality evidence). <b>5 </b>The ESGE recommends that the endoscopist is responsible for providing a written recommendation for the post-polypectomy surveillance schedule (strong recommendation, low quality evidence).
Relation of Ejection Fraction and Inducible Ventricular Tachycardia to Mode of Death in Patients With Coronary Artery Disease
Authors: Alfred E. Buxton, Kerry L. Lee, Gail E. Hafley, D. George Wyse, John D. Fisher, Michael H. Lehmann, Luis A. Pires, Michael R. Gold, Douglas L. Packer, Mark E. Josephson, Eric N. Prystowsky, Mario R. Talajic
Journal: Circulation (2002)

Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear.We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or > or =30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients, P=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction > or =30% (61% of events were arrhythmic among inducible patients with ejection fraction > or =30% and only 42% among noninducible patients, P=0.002).Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is > or =30%.
Nitrovasodilators and heart rate: more than the arterial baroreflex
Authors: P Musialek
Journal: Cardiovascular Research (2000)

Ẃe read with interest a recent study by Mesangeau et al. peripheral sympathetic neurotransmission by reducing the [1], which evaluates the development of cardiovascular synaptic release of noradrenaline [4,5].Moreover, both autonomic neuropathy in a pig model of streptozotocin-exogenous and endogenous NO may contribute to the induced diabetes.cholinergic antagonism of the positive chronotropic re-In addition to spectral analysis of short-term arterial sponse to adrenergic stimulation [6,7], possibly by interferblood pressure (ABP) and heart rate (HR) variability, this ing with the b-adrenergic signal transduction pathway in investigation involved determination of the baroreceptor-the sinoatrial node (see e.g.Ref.[8]).In addition, large HR reflex with vasoactive drugs.The sensitivity of the concentrations of exogenous NO can directly suppress baroreceptor-HR reflex was calculated by plotting the HR baroreceptor activity [9,10] and affect baroreflex transmisresponse to changes in ABP obtained by a graded infusion sion in the central nervous system (though the functional (40-60 min) of the a-adrenoceptor agonist phenylephrine relevance of these effects is still controversial; reviewed in (used to increase ABP) or of the nitrovasodilator sodiumRef. [11]).Finally, NO donors have been shown to directly nitroprusside (SNP; used to reduce ABP).(i.e.independent of their effects on the autonomic nervous As a further contribution to the discussion on the use of system) increase HR through a NO-cGMP-mediated nitrovasodilators to test baroreflex sensitivity [2], we stimulation of the pacemaker current I in isolated sinoatrif
siRNA Targeted to p53 Attenuates Ischemic and Cisplatin-Induced Acute Kidney Injury
Authors: Bruce A. Molitoris, Pierre C. Dagher, Ruben M. Sandoval, Silvia B. Campos, Hagit Ashush, Eduard Fridman, Anat Brafman, Alexander Faerman, Simon J. Atkinson, James D. Thompson, Hagar Kalinski, Rami Skaliter, Shai Erlich, Elena Feinstein
Journal: Journal of the American Society of Nephrology (2009)

Proximal tubule cells (PTCs), which are the primary site of kidney injury associated with ischemia or nephrotoxicity, are the site of oligonucleotide reabsorption within the kidney. We exploited this property to test the efficacy of siRNA targeted to p53, a pivotal protein in the apoptotic pathway, to prevent kidney injury. Naked synthetic siRNA to p53 injected intravenously 4 h after ischemic injury maximally protected both PTCs and kidney function. PTCs were the primary site for siRNA uptake within the kidney and body. Following glomerular filtration, endocytic uptake of Cy3-siRNA by PTCs was rapid and extensive, and significantly reduced ischemia-induced p53 upregulation. The duration of the siRNA effect in PTCs was 24 to 48 h, determined by levels of p53 mRNA and protein expression. Both Cy3 fluorescence and in situ hybridization of siRNA corroborated a short t(1/2) for siRNA. The extent of renoprotection, decrease in cellular p53 and attenuation of p53-mediated apoptosis by siRNA were dose- and time-dependent. Analysis of renal histology and apoptosis revealed improved injury scores in both cortical and corticomedullary regions. siRNA to p53 was also effective in a model of cisplatin-induced kidney injury. Taken together, these data indicate that rapid delivery of siRNA to proximal tubule cells follows intravenous administration. Targeting siRNA to p53 leads to a dose-dependent attenuation of apoptotic signaling, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury.
Segmental Aortic Stiffening Contributes to Experimental Abdominal Aortic Aneurysm Development
Authors: Uwe Raaz, Alexander M. Zöllner, Isabel N. Schellinger, Ryuji Toh, Futoshi Nakagami, Moritz Brandt, Fabian C. Emrich, Yosuke Kayama, Suzanne Eken, Matti Adam, Lars Maegdefessel, Thomas Hertel, Alicia Deng, Ann Jagger, Michael Buerke, Ronald L. Dalman, Joshua M. Spin, Ellen Kuhl, Philip S. Tsao
Journal: Circulation (2015)

Background— Stiffening of the aortic wall is a phenomenon consistently observed in age and in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. Methods and Results— Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening precedes aneurysm growth. Finite-element analysis reveals that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) wall stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent aortic segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with the reduced segmental stiffness of the AAA-prone aorta (attributable to equalized stiffness in adjacent segments), reduced axial wall stress, decreased production of reactive oxygen species, attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, and attenuated apoptosis within the aortic wall, as well. Cyclic pressurization of segmentally stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. Conclusions— The present study introduces the novel concept of segmental aortic stiffening as an early pathomechanism generating aortic wall stress and triggering aneurysmal growth, thereby delineating potential underlying molecular mechanisms and therapeutic targets. In addition, monitoring segmental aortic stiffening may aid the identification of patients at risk for AAA.
TC1 (C8orf4) Enhances the Wnt/β-Catenin Pathway by Relieving Antagonistic Activity of Chibby
Authors: Yusun Jung, Seunghyun Bang, Kyungho Choi, Eunsoon Kim, Youngmi Kim, Jungtae Kim, Juhee Park, Hyunlyoung Koo, Randall T. Moon, Kyuyoung Song, Inchul Lee
Journal: Cancer Research (2006)

Abstract The Wnt/β-catenin pathway has been implicated in human cancers. Here, we show that TC1 (C8orf4), a small protein present in vertebrates, functions as a positive regulator of the pathway. TC1 interacts with Chibby (Cby) and thereby enhances the signaling pathway by relieving the antagonistic function of Cby on the β-catenin–mediated transcription. Upon coexpression in mammalian cells, TC1 redistributes from nucleolus to nuclear speckles, where it colocalizes with Cby. TC1 up-regulates the expression of β-catenin target genes that are implicated in invasiveness and aggressive behavior of cancers, such as metalloproteinases, laminin γ2, and others. Our data indicate that TC1 is a novel upstream regulator of the Wnt/β-catenin pathway that enhances aggressive behavior of cancers. (Cancer Res 2006; 66(2): 723-8)
Surgical Duration and Risk of Venous Thromboembolism
Authors: John Y. S. Kim, Nima Khavanin, Aksharananda Rambachan, Robert J. McCarthy, Alexei S. Mlodinow, Gildasio S. De Oliveria, M. Christine Stock, Madeleine J. Gust, David M. Mahvi
Journal: JAMA Surgery (2014)

There is a paucity of data assessing the effect of increased surgical duration on the incidence of venous thromboembolism (VTE).To examine the association between surgical duration and the incidence of VTE.Retrospective cohort of 1,432,855 patients undergoing surgery under general anesthesia at 315 US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2011.Duration of surgery.The rates of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE within 30 days of the index operation. Surgical duration was standardized across Current Procedural Terminology codes using a z score. Outcomes were compared across quintiles of the z score. Multiple logistic regression models were developed to examine the association while adjusting for patient demographics, clinical characteristics, and comorbidities.The overall VTE rate was 0.96% (n = 13,809); the rates of DVT and PE were 0.71% (n = 10,198) and 0.33% (n = 4772), respectively. The association between surgical duration and VTE increased in a stepwise fashion. Compared with a procedure of average duration, patients undergoing the longest procedures experienced a 1.27-fold (95% CI, 1.21-1.34; adjusted risk difference [ARD], 0.23%) increase in the odds of developing a VTE; the shortest procedures demonstrated an odds ratio of 0.86 (95% CI, 0.83-0.88; ARD, -0.12%). The robustness of these results was substantiated with several sensitivity analyses attempting to minimize the effect of outliers, concurrent complications, procedural differences, and unmeasured confounding variables.Among patients undergoing surgery, an increase in surgical duration was directly associated with an increase in the risk for VTE. These findings may help inform preoperative and postoperative decision making related to surgery.
The Effect of Daily Oral Dosage of Diazepam, Plasma Concentrations and Metabolic Clearance of Diazepam and Demethyldiazepam on Various Constituents of the Acute Clinical Anxiety Syndrome
Authors: Haim Dasberg
Journal: Psychotherapy and Psychosomatics (1974)

The anxiolytic efficacy of oral diazepam, 20 mg daily, given for 5 days, as a short-term adjunctive treatment to crisis patients was not different from placebo, except for patients with high levels of anxiety. However, some specific symptoms are diazepam sensitive such as insomnia, respiratory, gastrointestinal complaints, and the cluster of the 'three main symptoms'. The minimal effective plasma concentration for these symptoms is 400 ng/ml of diazepam. <i>N</i>-demethyldiazepam levels of 300 ng/ml and above are disturbing. The main conclusion is that monitoring the dosage by checking plasma levels, as elsewhere in psychopharmacology (<i>Åsberg et al.,</i> 1971), seems advisable also for diazepam treatments of anxiety.
Rapid early weight gain is associated with wheeze and reduced lung function in childhood
Authors: A.C. van der Gugten, M. Koopman, A.M.V. Evelein, T.J.M. Verheij, C.S.P.M. Uiterwaal, C.K. van der Ent
Journal: European Respiratory Journal (2011)

The aim of our study was to investigate the association between rapid weight gain in the first 3 months of life and the prevalence of wheeze in the first years of life and lung function at 5 yrs of age. The infants selected were participating in an ongoing birth cohort. Information on growth and respiratory symptoms was collected during the first year of life, and on primary care consultations during total follow-up. Forced expiratory volume in 1 s (FEV 1 ) and forced expiratory flow at 25–75% of forced vital capacity (FEF 25–75% ) were measured at 5 yrs of age. Information on growth and respiratory symptoms was obtained for 1,431 infants, out of whom 235 children had already had 5 yrs of follow-up. Every one-point z-score increase in weight gain resulted in a 37% increase in days with wheeze (incidence rate ratio 1.37, 95% CI 1.27–1.47; p&lt;0.001) and in associated consultations by 16% (incidence rate ratio 1.16, 95% CI 1.01–1.34; p=0.04). Children with rapid weight gain reported significantly more physician-diagnosed asthma. FEV 1 and FEF 25–75% were reduced by 34 mL (adjusted regression coefficient -0.034, 95% CI -0.056– -0.013; p=0.002) and 82 mL (adjusted regression coefficient -0.082, 95% CI -0.140– -0.024; p=0.006) per every one-point z-score increase in weight gain, respectively. These associations were independent of birthweight. Rapid early weight gain is a risk factor for clinically relevant wheezing illnesses in the first years of life and lower lung function in childhood.
Increased Expression of the Polycomb Group Gene, <i>EZH2</i>, in Transitional Cell Carcinoma of the Bladder
Authors: Jay D. Raman, Nigel P. Mongan, Satish K. Tickoo, Stephen A. Boorjian, Douglas S. Scherr, Lorraine J. Gudas
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The Polycomb group gene, EZH2, functions as a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies, including prostate, breast, and lymphoma. We evaluated EZH2 mRNA and protein expression in bladder specimens from patients and the EZH2 mRNA expression in five bladder cancer cell lines. Experimental Design: EZH2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR) in 38 bladder tissue specimens. We also evaluated 39 bladder cancer specimens for EZH2 protein expression using immunohistochemistry with affinity-purified antibodies to human EZH2. In addition, five human bladder cancer cell lines were analyzed by RT-PCR for EZH2 mRNA expression. Results: Five of 14 (36%) nontumor bladder specimens versus 21 of 24 (88%) bladder tumors showed EZH2 mRNA expression (P = 0.003). All of the invasive tumors (10 of 10) had detectable EZH2 mRNA expression, compared with 11 of 14 (79%) superficial tumors. In addition, EZH2 mRNA expression was noted in 100% (16 of 16) of high-grade bladder tumors versus 50% (4 of 8) of low-grade tumors (P = 0.01). EZH2 protein expression, meanwhile, was increased in neoplastic tissue compared with nontumor urothelium (78% versus 69% of nuclei, P &amp;lt; 0.005). There were no differences in EZH2 protein levels between superficial and invasive tumors. High-grade tumors had increased EZH2 staining compared with normal urothelium (78% versus 68%, P &amp;lt; 0.005), whereas low-grade lesions did not. Four of five human bladder cancer cell lines expressed high levels of EZH2, whereas only low levels were detected in one cell line. Conclusions: We report a significant increase in EZH2 expression in transitional cell carcinoma of the bladder compared with normal urothelium. These data suggest that similar to other human malignancies, increased EZH2 expression correlates with oncogenesis of the bladder.