tbuckley/cabot-search huggingface dataset:
Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
Authors: W C Sessa, K Pritchard, N Seyedi, J Wang, T H Hintze
Journal: Circulation Research (1994)

Recently, we have shown that chronic exercise increases endothelium-derived relaxing factor (EDRF)/nitric oxide (NO)-mediated epicardial coronary artery dilation in response to brief occlusion and acetylcholine. This finding suggests that exercise can provide a stimulus for the enhanced production of EDRF/NO, thus possibly contributing to the beneficial effects of exercise on the cardiovascular system. Therefore, the purpose of the present study was to examine whether chronic exercise could influence the production of NO (measured as the stable degradation product, nitrite) and endothelial cell NO synthase (ECNOS) gene expression in vessels from dogs after chronic exercise. To this end, dogs were exercised by running on a treadmill (9.5 km/h for 1 hour, twice daily) for 10 days, and nitrite production in large coronary vessels and microvessels and ECNOS gene expression in aortic endothelial extracts were assessed. Acetylcholine (10(-7) to 10(-5) mol/L) dose-dependently increased the release of nitrite (inhibited by nitro-L-arginine) from coronary arteries and microvessels in control and exercised dogs. Moreover, acetylcholine-stimulated nitrite production was markedly enhanced in large coronary arteries and microvessels prepared from hearts of dogs after chronic exercise compared with hearts from control dogs. One potential mechanism that may contribute to the enhanced production of nitrite in vessels from exercised dogs may be the induction of the calcium-dependent ECNOS gene. Steady-state mRNA levels for ECNOS were significantly higher than mRNA levels for von Willebrand's factor (vWF, a specific endothelial cell marker) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a constitutively expressed gene) in exercised dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
The Evolution of the Pheromonal Signal System and Its Potential Role for Reproductive Isolation in Heterothallic Neurospora
Authors: Magnus Karlsson, Kristiina Nygren, Hanna Johannesson
Journal: Molecular Biology and Evolution (2007)

Comparative sequencing studies among a wide range of taxonomic groups, including fungi, provide the overall pattern that reproductive genes evolve more rapidly than other genes, and this divergence is believed to be important in the establishment of reproductive barriers between species. In this study, we investigated the molecular evolution of the pheromone receptor genes pre-1 and pre-2 of strains belonging to 12 and 13 heterothallic taxa, respectively, of the model genus Neurospora. Furthermore, we examined the regulatory pattern of both pheromone precursor and receptor genes during sexual crosses of Neurospora crassa and Neurospora intermedia, for which reinforcement of interspecific reproductive barriers in sympatry previously has been documented. We conclude that the part encoding the C-terminal intracellular domain of pre-1 and pre-2 genes evolves rapidly. Both stochastic and directional processes drive this divergence; both genes contain neutrally evolving codons, and in addition, pre-1 contains codons evolving under positive selection, whereas in pre-2 we found highly variable regions with numerous repeats encoding glycine, threonine, or aspartic acid. In addition, we found regulatory changes of the pheromone and receptor genes during crosses between N. crassa and N. intermedia with different reproductive success. Gene expression levels are higher in the interspecific sympatric crosses with low reproductive success than in their intraspecific and/or allopatric equivalents, both at the stage of initial communication and contact and later at postfertilization stages. Taken together, our data indicate that pheromones and receptors are important key players during reproductive isolation between Neurospora species, and this study provides a general framework for future studies on the role of reproductive proteins for reproductive isolation.
Short-Term Effects of PM <sub>10</sub> and NO <sub>2</sub> on Respiratory Health among Children with Asthma or Asthma-like Symptoms: A Systematic Review and Meta-Analysis
Authors: Gudrun Weinmayr, Elisa Romeo, Manuela De Sario, Stephan K. Weiland, Francesco Forastiere
Journal: Environmental Health Perspectives (2009)

Our goal was to quantify the short-term effects of particulate matter with aerodynamic diameter < or = 10 microm (PM10) and nitrogen dioxide (NO2) on respiratory health of asthmatic children from published panel studies, and to investigate the influence of study and population characteristics as effect modifiers.After a systematic literature review, we extracted quantitative estimates of the association of PM10 and/or NO2 with respiratory symptoms and peak expiratory flow (PEF). Combined effect estimates for an increase of 10 microg/m3 were calculated by random effects meta-analysis for all studies and for different strata defined by study characteristics. The effect of publication bias was investigated with Egger's and Begg's tests and "trim-and-fill" analyses.We identified 36 studies; 14 were part of the European Pollution Effects on Asthmatic Children in Europe (PEACE) study. Adverse associations of PM10 with asthma symptoms were statistically significant [odds ratio (OR) = 1.028; 95% confidence interval (CI), 1.006-1.051]. There were also associations, although not statistically significant, of PM10 with cough (OR = 1.012; 95% CI, 0.997-1.026) and on PEF (decrease of -0.082 L/min; 95% CI, -0.214 to 0.050). NO2 had statistically significant associations with asthma symptoms in the overall analysis considering all possible lags (OR = 1.031; 95% CI, 1.001-1.062), but not when we evaluated only the 0-1 lag. We found no publication bias, although it appeared when excluding the PEACE studies. When we applied the trim-and-fill method to the data set without the PEACE studies, the results were similar to the overall estimates from all studies. There was an indication for stronger PM10 associations for studies conducted in summer, outside of Europe, with longer lags, and in locations with higher NO2 concentrations.We found clear evidence of effects of PM10 on the occurrence of asthma symptom episodes, and to a lesser extent on cough and PEF. The results for NO2 are more difficult to interpret because they depend on the lag times examined. There was an indication of effect modification by several study conditions.
Spontaneous Hypoglycaemia and Epilepsy: Subtotal Pancreatectomy
Authors: N. G. Hulbert, R. J. M. Love
Journal: BMJ (1946)

Reports of cases of spontaneous hypoglycaemia treated by partial pancreatectomy are uncommon in this country, although American literature contains numerous accounts of the surgical treatment of pancreatic hyperactivity.The case herewith reported is of interest in that the symptoms of hypoglycaemia were associated with epilepsy, which confused the clinical picture in the earlier stages of the illness.Although, most unfortunately, the patient succumbed from pulmonary infarction, he lived long enough to demonstrate the remarkable improvement which followed subtotal pancreatectomy. Case HistoryIn 1922 the patient, then aged 41, had his first fit.He had just begun his morning's work when without warning he fell on his face unconscious.He understood that he lay quite still, was uncertain if he bit his tongue, but remembered having wetted his trousers."He was taken home unconscious.His doctor said that his heart was in a bad state and that he smoked excessively.During the same day he had three further fits, with twitching movements all over the body, and believed that he remained unconscious for some seven hours in all.A doctor again examined him that evening and the following day.He then referred him to one of the larger London teaching hospitals.Here his skull was x-rayed in three positions and a blood test taken.
Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes
Authors: Martin U Braun, Palma Szalai, Ruth H Strasser, Mathias M Borst
Journal: Cardiovascular Research (2003)

Pressure overload induced by pulmonary artery banding (PAB) leads to right ventricular (RV) hypertrophy and cardiomyocyte apoptosis. The present study was performed to investigate whether protein kinase C isozymes (PKC-alpha, PKC-betaI, PKC-betaII, PKC-delta and PFC- epsilon ), calcineurin and the renin-angiotensin system (RAS) contribute to PAB-induced cardiac remodeling.PAB in male Wistar rats for 3 weeks results in enhanced PKC activity (as determined by ELISA assay) in the cytosol and membrane fraction of the hypertrophied RV, which was accompanied by increased expression (as determined by Western blot analysis) of cytosolic PKC-delta (+72%), PKC-alpha (+49%), and PKC-betaI (+39%), but not PKC-betaII and PKC- epsilon. This differential regulation of cardiac PKC isozymes was limited to the strained ventricle and was not altered in response to chronic angiotensin-converting enzyme inhibition with ramiprilate. Furthermore, no significant changes in the expression of calcineurin alpha and beta subunits were observed in RV pressure overload compared to controls. PAB-induced cardiac apoptosis was determined using Western blot analysis by a significantly increased expression of Bax protein and caspase-3 in the hypertrophied RV, which was diminished to almost control levels by chronic ramiprilate treatment. The myocardial expression of Bcl-2 was not significantly altered in the experimental groups.We have shown for the first time that PAB-induced RV hypertrophy is associated with a differential regulation of cardiac PKC isozymes independent of the RAS and further provide evidence for a pivotal role of the RAS in the development of PAB-induced cardiac apoptosis.
Three Major Loci Involved in Age-Related Macular Degeneration Are Also Associated with Polypoidal Choroidal Vasculopathy
Authors: Luiz H. Lima, Carl Schubert, Daniela C. Ferrara, Joanna E. Merriam, Yutaka Imamura, K. Bailey Freund, Richard F. Spaide, Lawrence A. Yannuzzi, Rando Allikmets
Journal: Ophthalmology (2010)
Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis
Authors: C Turesson, R L McClelland, T J H Christianson, E L Matteson
Journal: Annals of the Rheumatic Diseases (2006)

<h3>ABSTRACT</h3> Glioblastoma multiforme (GBM) is the most commonly diagnosed brain cancer in adults, characterized by rapid proliferation and aggressive invasion into the stroma. Advances in our understanding of the molecular subtypes of GBM have provided attractive druggable targets. However, the high degree of heterogeneity both among patients and within individual tumors has proven a significant challenge for the development of effective therapies. We hypothesized that this heterogeneity is also represented in the mechanical phenotypes of GBM, as the physical properties of tumor tissue strongly influence elements of tumor progression including cell cycle regulation, migration, and therapeutic resistance. To assess these phenotypes, we employed optical trap-based active microrheology to determine the viscoelastic properties of patient-derived GBM cells in 3D hydrogels mimicking the brain ECM. We found that each GBM cell line had a distinct rheological profile as a function of treatment status, and cell lines could be further characterized by strong power law dependence describing intracellular viscoelastic behavior. Single-cell phenotyping according to power law dependence was able to identify subpopulations of cells within the treatment-resistant line. Finally, proteomic analysis indicated that altered mechanical profiles were associated with differential cytoskeletal regulation, particularly in actin - and myosin-binding pathways. This work suggests that evaluating mechanical properties may serve as a valuable strategy for the further stratification of these tumors, and encourages the investigation of cytoskeleton regulation as a potential therapeutic target for GBM.
Notch1-induced T cell leukemia can be potentiated by microenvironmental cues in the spleen
Authors: Shihui Ma, Yingxu Shi, Yakun Pang, Fang Dong, Hui Cheng, Sha Hao, Jing Xu, Xiaofan Zhu, Weiping Yuan, Tao Cheng, Guoguang Zheng
Journal: Journal of Hematology & Oncology (2014)

Leukemia is a systemic malignancy originated from hematopoietic cells. The extracellular environment has great impacts on the survival, proliferation and dissemination of leukemia cells. The spleen is an important organ for extramedullary hematopoiesis and a common infiltration site in lymphoid malignancies. Splenomegaly, frequently observed in T cell acute lymphoblastic leukemia (T-ALL), is associated with poor prognosis. However, how the spleen microenvironment distinctly affects T-ALL cells as opposed to bone marrow (BM) microenvironment has not been addressed. A Notch1-induced mouse T-ALL model was applied in this study. Flow cytometry and two-photon fluorescence microscopy were used to analyze early distribution of T-ALL cells. MILLIPLEX® MAP Multiplex Immunoassay was performed to measure cytokine/chemokine levels in different microenvironments. Transwell and co-culture experiments were used to test the effects of splenic microenvironment in vitro. Splenectomy was performed to assess the organ specific impact on the survival of T-ALL-bearing mice. More leukemia cells were detected in the spleen than in the BM after injection of T-ALL cells by flow cytometry and two-photon fluorescence microscopy analysis. By screening a panel of cytokines/chemokines, a higher level of MIP-3β was found in the splenic microenvironment than BM microenvironment. In vitro transwell experiment further confirmed that MIP-3β recruits T-ALL cells which express a high level of MIP-3β receptor, CCR7. Furthermore, the splenic microenvironment stimulates T-ALL cells to express a higher level of MIP-3β, which further recruits T-ALL cells to the spleen. Co-culture experiment found that the splenic microenvironment more potently stimulated the proliferation and migration of T-ALL cells than BM. Moreover, the mice transplanted with T-ALL cells from the spleen had a shorter life span than those transplanted from BM, suggesting increased potency of the T-ALL cells induced by the splenic microenvironment. In addition, splenectomy prolonged the survival of leukemic mice. Our study demonstrates an organ specific effect on leukemia development. Specifically, T-ALL cells can be potentiated by splenic microenvironment and thus spleen may serve as a target organ for the treatment of some types of leukemia.
Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases
Authors: I. Borg, G. Rohde, S. Löseke, J. Bittscheidt, G. Schultze-Werninghaus, V. Stephan, A. Bufe
Journal: European Respiratory Journal (2003)

Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract infections (ARI) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD and the viral load in different respiratory diseases has not been investigated to date. The present authors established and evaluated a quantitative TaqMan® real-time polymerase chain reaction assay specific for RSV subgroup A. Absolute quantification for the determination of viral load input was achieved using a control plasmid. The assay allowed for a quantification over a &gt;6-log range and a detection limit of &lt;10 RSV copies per reaction mixture. The assay was 30 times more sensitive than conventional nested polymerase chain reaction assays. Interassay sd was 1.3 and coefficient of variation 4.7% on average. Clinical specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were compared for viral loads. A total of 47% RSV-positive samples were found in the ARI study group and 28% in the COPD study group. The viral load of both study groups was found to differ significantly. In the ARI study group the viral load was increased almost 2000-fold, suggesting acute infection in this group and former or latent infection in the COPD group. Respiratory syncytial virus-A specific TaqMan® real-time polymerase chain reaction assay is a sensitive and rapid method for the determination of viral load in clinical samples. It enables differential statements concerning the involvement of respiratory syncytial virus in acute lower respiratory tract infections and chronic obstructive pulmonary disease to be achieved.
Urodilatin, a kidney-derived natriuretic factor, is excreted with a circadian rhythm and is stimulated by saline infusion in man.
Authors: C Drummer, F Fiedler, A König, R Gerzer
Journal: Journal of the American Society of Nephrology (1991)

Urodilatin is a recently described, presumably kidney-derived member of the atrial natriuretic peptide family. The first data on a physiological role for urodilatin in the regulation of sodium homeostasis in humans is presented in this work. Urinary urodilatin excretion during a 9-day study in healthy volunteers paralleled the circadian rhythm in urinary sodium excretion. Furthermore, urodilatin and sodium excretion were slightly increased during the first 3 h after an acute isotonic saline infusion and about three-fold elevated during 14 h postinfusion; both parameters remained closely correlated up to 28 h postinfusion. These data suggest that urodilatin is involved in the circadian regulation of sodium excretion and is a physiological regulator of long-term sodium excretion after an acute saline infusion.
Genetic association studies of interleukin-13 receptor 1 subunit gene polymorphisms in asthma and atopy
Authors: A. K. Konstantinidis, S. J. Barton, I. Sayers, I. A. Yang, J. L. Lordan, S. Rorke, J. B. Clough, S. T. Holgate, J. W. Holloway
Journal: European Respiratory Journal (2007)

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor α1 subunit (IL-13Rα1) and IL-4Rα. The genetic diversity at the IL-13Rα1 gene ( IL13RA1 ) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case–control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T&gt;G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A&gt;G variant in the IL13RA1 proximal 3′ untranslated region. No significant association of either -281T&gt;G or 1365A&gt;G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor α1 subunit gene -281T&gt;G and 1365A&gt;G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor α1 subunit gene locus might be involved in the control of immunoglobulin E production.
Endothelin-Mediated Positive Inotropic Effect Induced by Reactive Oxygen Species in Isolated Cardiac Muscle
Authors: Gilles W. De Keulenaer, Luc J. Andries, Stanislas U. Sys, Dirk L. Brutsaert
Journal: Circulation Research (1995)

Abstract Cardiac endothelium, both coronary and endocardial, produces a number of inotropic molecules. Changes in cardiac endothelial function by substances in the superfusing blood may thus participate in the control of muscle-pump performance of the heart. Reactive oxygen species (ROS) have been implicated in normal and pathological vascular physiology by influencing vascular endothelial function. Therefore, we examined the influence of ROS on endocardial endothelial modulation of myocardial performance. Right ventricular cat papillary muscles were briefly (15 s) exposed to electrolysis-generated ROS. Peak total isometric twitch tension and peak rate of tension development increased by 7.8±0.7% ( P &lt;.05) and 9.7±1.5% ( P &lt;.05), respectively (n=12). Isometric twitch duration was slightly increased (time from stimulus to half isometric relaxation, +2.7±0.6%; P &lt;.05). ROS scavengers such as ascorbic acid (n=6), superoxide dismutase and catalase (n=8), or catalase alone (n=6), but not superoxide dismutase alone (n=6), blocked the inotropic effect. Interestingly, the positive inotropic effect was completely blocked by selectively damaging endocardial endothelium (Triton X-100, 0.5%, 1-s immersion, n=7) before ROS generation and by preincubating the muscles with the endothelin-A receptor antagonist BQ 123 (n=11). Preincubation with N G -nitro- l -arginine methyl ester and indomethacin (n=5) or with atenolol (n=6) did not influence the inotropic effect. Confocal scanning laser microscopic observations of muscles stained with viability tracers (n=9) revealed that significantly more but not all endocardial endothelial cells were damaged in electrolysis-treated muscles than in control muscles (42±5% versus 14±4%, P &lt;.05). Accordingly, brief exposure of isolated cardiac muscle to electrolysis-generated ROS damaged the endocardial surface in part and increased contractile performance by stimulating endothelin release from endocardial endothelium. Hence, ROS-induced endothelin release from endocardial endothelium may be involved in normal and/or disturbed regulation of cardiac function.
Impact of Renal Insufficiency on Short-Term Morbidity and Mortality after Lower Extremity Revascularization
Authors: Ann M. O’Hare, Joe Feinglass, Anton N. Sidawy, Peter Bacchetti, Rudolph A. Rodriguez, Jennifer Daley, Shukri Khuri, William G. Henderson, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2003)

Few data are available on the impact of renal insufficiency on short-term operative outcomes after lower extremity surgical revascularization. We used prospectively collected data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to explore the association with renal dysfunction of adverse outcomes occurring within 30 d of lower extremity surgical revascularization in a cohort of all patients undergoing at least one lower extremity surgical revascularization from 1/1/94 to 9/30/01 (n = 18,217). Even moderate renal insufficiency (estimated GFR 30-59cc/min/1.73m(2)) was associated with an increased incidence of postoperative death (adjusted odds ratio (OR) 1.44, 95% confidence interval (CI), 1.17 to 1.77, P = 0.001), cardiac arrest (OR 1.43, CI 1.09 to 1.88, P = 0.011), myocardial infarction (OR 1.68, 1.39 to 2.16, P < 0.001), unplanned intubation (OR 1.69, CI 1.39 to 2.07, P < 0.001) and prolonged intubation (OR 1.57, CI 1.28 to 1.94, P < 0.001) within 30 d of lower extremity revascularization. However, the incidence of wound infection and graft failure requiring return to the operating room did not appear to be substantially higher in this group. Our data also show that patients with renal insufficiency undergoing revascularization were more likely to require distal procedures and to present with limb-threatening infection compared to those with normal renal function. Efforts to improve pre-and post-operative care in patients with renal insufficiency undergoing lower extremity revascularization should take into account the increased incidence of postoperative death and cardiopulmonary complications in this group in addition to more traditional concerns about operative site complications. Further studies are needed to explore reasons for the higher rate of limb-threatening infection in patients with renal insufficiency undergoing revascularization.